Morbidity and prostate-specific antigen control of external beam radiation therapy plus low-dose-rate brachytherapy boost for low, intermediate, and high-risk prostate cancer.

PubMed

Koontz, Bridget F; Chino, Junzo; Lee, W Robert; Hahn, Carol A; Buckley, Niall; Huang, Samuel; Kim, Jay; Reagan, Robert; Joyner, Raymond; Anscher, Mitchell S

2009-01-01

Dose escalation has been shown beneficial in prostate cancer. Brachytherapy (BT) provides an opportunity for dose escalation beyond what can be safely delivered using only teletherapy methods. The purpose of this study was to determine cancer control and morbidity of external beam radiation therapy (EBRT) plus low-dose-rate (LDR) BT boost in patients with prostate cancer treated at Duke University Health System. Between June 1997 and August 2007, 199 patients were consecutively treated at our facility with 46Gy EBRT followed by 100Gy palladium-103 ((103)Pd) or 120Gy iodine-125 ((125)I) LDR prostate implant. Treatment characteristics and followup data were retrospectively analyzed. Intermediate risk was defined as T2b-c, Gleason score 7 (GS 7), or prostate-specific antigen (PSA) of 10.1-19.9ng/mL. High risk was defined as GS 8-10, PSA>20, T3+, or two intermediate risk factors. The Radiation Therapy Oncology Group toxicity scale was used to report morbidity for gastrointestinal (GI) and genitourinary (GU) effects. PSA recurrence was defined as nadir+2ng/mL. Median followup was 4.2 years for all patients, 4.8 years for high-risk patients. Risk categories were as follows: 20% low risk, 47% intermediate risk, and 33% high risk. Forty five percent of patients received adjuvant androgen deprivation therapy (ADT). The median length of time since end of ADT to last followup was 2.7 years in all patients, 2.0 years for high-risk patients. Five-year biochemical relapse-free survival was 87% for all, 81% for high-risk patients. PSA control was similar at 92% for all and 86% for high-risk patients. Five-year actuarial risk of any and Grade 3 late GI morbidity was 38% and 7% respectively, and any and Grade 3 late GU morbidity was 21% and 3%, respectively. There were no significant differences in risk of Grade 2+GI or GU morbidity with choice of isotope. EBRT plus LDR BT has acceptable morbidity and, with 5-year followup, provides excellent cancer control even in high-risk patients.

Predictors of Prostate Cancer-Specific Mortality in Elderly Men With Intermediate-Risk Prostate Cancer Treated With Brachytherapy With or Without External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nanda, Akash, E-mail: ananda@partners.or; Chen, M.-H.; Moran, Brian J.

2010-05-01

Purpose: To identify clinical factors associated with prostate cancer-specific mortality (PCSM), adjusting for comorbidity, in elderly men with intermediate-risk prostate cancer treated with brachytherapy alone or in conjunction with external beam radiation therapy. Methods and Materials: The study cohort comprised 1,978 men of median age 71 (interquartile range, 66-75) years with intermediate-risk disease (Gleason score 7, prostate-specific antigen (PSA) 20 ng/mL or less, tumor category T2c or less). Fine and Gray's multivariable competing risks regression was used to assess whether prevalent cardiovascular disease (CVD), age, treatment, year of brachytherapy, PSA level, or tumor category was associated with the risk ofmore » PCSM. Results: After a median follow-up of 3.2 (interquartile range, 1.7-5.4) years, the presence of CVD was significantly associated with a decreased risk of PCSM (adjusted hazard ratio, 0.20; 95% CI 0.04-0.99; p = 0.05), whereas an increasing PSA level was significantly associated with an increased risk of PCSM (adjusted hazard ratio 1.14; 95% CI 1.02-1.27; p = 0.02). In the absence of CVD, cumulative incidence estimates of PCSM were higher (p = 0.03) in men with PSA levels above as compared with the median PSA level (7.3 ng/mL) or less; however, in the setting of CVD there was no difference (p = 0.27) in these estimates stratified by the median PSA level (6.9 ng/mL). Conclusions: In elderly men with intermediate-risk prostate cancer, CVD status is a negative predictor of PCSM and affects the prognostic capacity of pretreatment PSA level. These observations support the potential utility of prerandomization stratification by comorbidity to more accurately assess prognostic factors and treatment effects within this population.« less

Use of Age and Medical Comorbidity to Assess Long-term Other-cause Mortality Risk in a Cohort of Men Undergoing Prostate Biopsy at an Academic Medical Center.

PubMed

Kominsky, Hal D; Bashline, Michael; Eun, Daniel; Pontari, Michel A; Mydlo, Jack H; Reese, Adam C

2017-02-01

To assess life expectancy and biopsy outcomes in men undergoing prostate biopsy at an academic medical center. We analyzed men who underwent prostate biopsy at our medical center between July 2012 and June 2014. Long-term other-cause mortality risk was determined using survival tables. Indications for biopsy and biopsy outcomes were assessed, and compared among men with varying mortality risks. A total of 417 men underwent prostate biopsy, in whom 14-year other-cause mortality risk ranged from 9% to 74%. One hundred ninety-three men (46.3%) were considered low-mortality risk (<40% risk of 14-year mortality), 131 (31.4%) intermediate risk (41%-55% 14-year mortality), and 93 (22.3%) high risk (>55% 14-year mortality). Of the 417 patients who underwent biopsy, 149 (35.7%) were found to have prostate cancer. There was no significant difference in the rate of positive biopsies (P = .72), distribution of Gleason scores (P = .60), or percentage of positive biopsy cores (P = .74) between mortality risk groups. However, by UCSF Cancer of the Prostate Risk Assessment score, there was significant trend toward higher-risk prostate cancer in men with intermediate and high-mortality risk (P = .04). In this analysis, a large number of men with limited life expectancies underwent prostate biopsy. The majority of these men had negative biopsies or low-risk cancers, suggesting that they were unlikely to benefit from biopsy. To avoid potentially unnecessary prostate biopsies, the practitioner must give serious consideration to a patient's age and medical comorbidities before making a recommendation as to whether biopsy should be performed. Copyright © 2016 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castle, Katherine O., E-mail: kocastle@mdanderson.org; Hoffman, Karen E.; Levy, Lawrence B.

Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis basedmore » on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease. In patients with GS 4+3 or T2c disease, the addition of ADT to dose-escalated RT did improve FFF.« less

Three-month posttreatment prostate-specific antigen level as a biomarker of treatment response in patients with intermediate-risk or high-risk prostate cancer treated with androgen deprivation therapy and radiotherapy.

PubMed

Bryant, Alex K; D'Amico, Anthony V; Nguyen, Paul L; Einck, John P; Kane, Christopher J; McKay, Rana R; Simpson, Daniel R; Mundt, Arno J; Murphy, James D; Rose, Brent S

2018-05-04

Prostate-specific antigen (PSA) measurement after definitive radiotherapy (RT) and androgen deprivation therapy for localized prostate cancer has been proposed as an early prognostic biomarker. In the current study, the authors investigated the association between 3-month post-RT PSA level and biochemical progression-free survival (bPFS), prostate cancer-specific survival (PCSS), and overall survival (OS). A total of 5783 patients with intermediate-risk or high-risk localized prostate cancer who were diagnosed between 2000 and 2015 and treated with RT and androgen deprivation therapy were identified from Veterans Affairs data. Patients were divided into groups based on 3-month post-RT PSA values: <0.10 ng/mL, 0.10 to 0.49 ng/mL, and ≥0.50 ng/mL. The effect of the 3-month PSA group on bPFS, PCSS, and OS was evaluated in multivariable Cox models adjusting for potential confounders. There were 2651 patients with intermediate-risk and 3132 with high-risk disease; approximately 11% had a 3-month PSA level of ≥0.50 ng/mL. A higher 3-month PSA level was found to be strongly associated with each outcome; compared with patients in the group with a 3-month PSA value <0.10 ng/mL, the authors noted greater hazards for the patients with a 3-month PSA value ≥0.50 ng/mL (hazard ratio for bPFS: 5.23; PCSS: 3.97; and OS: 1.50 [P<.001 for all]) and the patients with a 3-month PSA value of 0.10 to 0.49 ng/mL (hazard ratio for bPFS: 2.41 [P<.001]; PCSS: 2.29 [P<.001]; and OS: 1.21 [P = .003]). When analyzed separately, the 3-month PSA level was found to be predictive of OS in the high-risk group (P<.001) but not the intermediate-risk group (P = .21). The 3-month post-RT PSA level appears to be a strong prognostic biomarker for bPFS, PCSS, and OS in patients with intermediate-risk and high-risk prostate cancer, particularly those with high-risk disease. The 3-month PSA measurement may augment clinical decision making and holds promise as a potential surrogate endpoint in clinical trials. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

High-Intensity Focused Ultrasound in Treating Participants With Intermediate and High-risk Prostate Cancer

ClinicalTrials.gov

2018-06-13

Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIA Prostate Cancer AJCC v8; Stage IIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8

Conventional Versus Automated Implantation of Loose Seeds in Prostate Brachytherapy: Analysis of Dosimetric and Clinical Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Genebes, Caroline, E-mail: genebes.caroline@claudiusregaud.fr; Filleron, Thomas; Graff, Pierre

2013-11-15

Purpose: To review the clinical outcome of I-125 permanent prostate brachytherapy (PPB) for low-risk and intermediate-risk prostate cancer and to compare 2 techniques of loose-seed implantation. Methods and Materials: 574 consecutive patients underwent I-125 PPB for low-risk and intermediate-risk prostate cancer between 2000 and 2008. Two successive techniques were used: conventional implantation from 2000 to 2004 and automated implantation (Nucletron, FIRST system) from 2004 to 2008. Dosimetric and biochemical recurrence-free (bNED) survival results were reported and compared for the 2 techniques. Univariate and multivariate analysis researched independent predictors for bNED survival. Results: 419 (73%) and 155 (27%) patients with low-riskmore » and intermediate-risk disease, respectively, were treated (median follow-up time, 69.3 months). The 60-month bNED survival rates were 95.2% and 85.7%, respectively, for patients with low-risk and intermediate-risk disease (P=.04). In univariate analysis, patients treated with automated implantation had worse bNED survival rates than did those treated with conventional implantation (P<.0001). By day 30, patients treated with automated implantation showed lower values of dose delivered to 90% of prostate volume (D90) and volume of prostate receiving 100% of prescribed dose (V100). In multivariate analysis, implantation technique, Gleason score, and V100 on day 30 were independent predictors of recurrence-free status. Grade 3 urethritis and urinary incontinence were observed in 2.6% and 1.6% of the cohort, respectively, with no significant differences between the 2 techniques. No grade 3 proctitis was observed. Conclusion: Satisfactory 60-month bNED survival rates (93.1%) and acceptable toxicity (grade 3 urethritis <3%) were achieved by loose-seed implantation. Automated implantation was associated with worse dosimetric and bNED survival outcomes.« less

High-Dose-Rate Brachytherapy as Monotherapy for Intermediate- and High-Risk Prostate Cancer: Clinical Results for a Median 8-Year Follow-Up

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshioka, Yasuo, E-mail: yoshioka@radonc.med.osaka-u.ac.jp; Suzuki, Osamu; Isohashi, Fumiaki

2016-03-15

Purpose: To present mature results of high-dose-rate brachytherapy (HDR-BT) as monotherapy for intermediate- and high-risk prostate cancer. Methods and Materials: From 1995 through 2012, 190 patients, 79 with intermediate-risk and 111 with high-risk prostate cancer, were treated with HDR-BT alone using 48 Gy/8 fractions, 54 Gy/9 fractions, or 45.5 Gy/7 fractions over 4 to 5 days. Neoadjuvant with or without adjuvant androgen deprivation therapy was administered to 139 patients, 35 intermediate- and 104 high-risk. Results: Median follow-up time was 92 months (range, 10-227 months), with a minimum of 2 years for surviving patients. Respective rates of cause-specific survival, overall survival, metastasis-free survival, and biochemical no evidence ofmore » disease for the intermediate-risk patients were 100%, 100%, 96%, and 93% at 5 years, and 100%, 96%, 91%, and 91% at 8 years. Corresponding rates for the high-risk patients were 97%, 93%, 84%, and 81% at 5 years, and 93%, 81%, 74%, and 77% at 8 years. The cumulative incidence of late grade 2 to 3 genitourinary toxicity was 5% at 5 years and 10% at 8 years, and that of late grade 3 was 0 at 5 years and 1% at 8 years. The cumulative incidence of late grade 2-3 gastrointestinal toxicity was 4% at 5 years and 6% at 8 years, and that of late grade 3 was 0 at 5 years and 2% at 8 years. No grade 4 or 5 toxicity was detected. Conclusions: Our single-institution study with a median 8-year follow-up showed that HDR-BT as monotherapy was safe and effective for patients with intermediate- and high-risk prostate cancer.« less

Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zumsteg, Zachary S.; Spratt, Daniel E.; Pei, Xin

2013-03-15

Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likelymore » to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.« less

Lack of Benefit for the Addition of Androgen Deprivation Therapy to Dose-Escalated Radiotherapy in the Treatment of Intermediate- and High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krauss, Daniel, E-mail: dkrauss@beaumont.edu; Kestin, Larry; Ye, Hong

2011-07-15

Purpose: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). Methods and Materials: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA {>=}20, or Stage T3. Patients were additionally divided specifically by Gleason score, presencemore » of palpable disease, and PSA level to further define subgroups benefitting from ADT. Results: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason {>=}8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. Conclusion: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.« less

Clinical outcomes of whole pelvis radiotherapy and stereotactic body radiotherapy boost for intermediate- and high-risk prostate cancer.

PubMed

Kim, Hun Jung; Phak, Jeong Hoon; Kim, Woo Chul

2017-10-01

We report our experience with Cyberknife to deliver hypofractionated stereotactic body radiotherapy (SBRT) boost combined with whole pelvis radiotherapy (WPRT) to patients with intermediate- to high-risk prostate cancer. From March 2008 to July 2014, 39 patients with newly diagnosed, intermediate- and high-risk (National Comprehensive Cancer Network definition) localized prostate cancer were treated with WPRT and SBRT boost. The whole pelvis dose was 45 Gy (25 fractions of 1.8 Gy) and the SBRT boost dose was 21 Gy (3 fractions of 7 Gy). No one received androgen deprivation therapy before biochemical relapse. The acute and late toxicities were recorded using the Radiation Therapy Oncology Group scale. Prostate-specific antigen (PSA) response was monitored. Thirty-nine patients with a median 53.6 months (range 14-74 months) follow-up were analyzed. The median pretreatment PSA was 15.97 ng/mL. The estimated 5-year biochemical failure (BCF)-free survival was 94.7%. Two BCFs were observed in only high-risk group. The median PSA nadir was 0.30 ng/mL at median 36 months and PSA bounce occurred in 15.4% (n = 6) of patients at median 12 months. No grade 3 acute toxicity was noted. A total of 23% of the patients had grade 2 acute genitourinary (GU) toxicities and 21% had grade 2 acute gastrointestinal (GI) toxicities. At 2 months, most complications had returned to baseline. GU and GI toxicities were observed. WPRT followed by SBRT boost using Cyberknife in intermediate- and high-risk prostate cancer is feasible with minimal toxicity and encouraging BCF-free survival. © 2016 John Wiley & Sons Australia, Ltd.

Effect of Long-Term Hormonal Therapy (vs Short-Term Hormonal Therapy): A Secondary Analysis of Intermediate-Risk Prostate Cancer Patients Treated on NRG Oncology RTOG 9202

PubMed Central

Mirhadi, Amin J.; Zhang, Qiang; Hanks, Gerald E.; Lepor, Herbert; Grignon, David J.; Peters, Christopher A.; Rosenthal, Seth A.; Zeitzer, Kenneth; Radwan, John S.; Lawton, Colleen; Parliament, Matthew B.; Reznik, Robert S.; Sandler, Howard M.

2017-01-01

Purpose NRG Oncology RTOG 9202 was a randomized trial testing long-term adjuvant androgen deprivation (LTAD) versus initial androgen deprivation only (STAD) with external beam radiation therapy (RT) in mostly high-risk and some intermediate-risk prostate cancer patients. RTOG 9408 found an overall survival (OS) advantage in patients with cT1b-T2b disease and prostate-specific antigen (PSA) <20 ng/mL, with benefit observed mostly among intermediate-risk patients. It was still unknown whether intermediate-risk patients would experience an additional survival benefit with LTAD; thus, we performed a secondary analysis to explore whether LTAD had any incremental benefit beyond STAD among the intermediate-risk subset of RTOG 9202. The study endpoints were OS, disease-specific survival (DSS), and PSA failure (PSAF). Methods and Materials An analysis was performed for all patients enrolled in RTOG 9202 defined as intermediate-risk (cT2 disease, PSA<10 ng/mL, and Gleason score = 7 or cT2 disease, PSA 10-20 ng/mL, and Gleason score <7). This review yielded 133 patients: 74 (STAD) and 59 (LTAD). The Kaplan-Meier method was used to estimate OS; the cumulative incidence approach was used to estimate DSS and PSAF. A 2-sided test was used, with significance level defined to be .05. Results With over 11 years of median follow-up, 39 STAD patients were alive and 33 LTAD patients were alive. There was no difference in OS (10-year estimates, 61% STAD vs 65% LTAD; P=.53), DSS (10-year DSS, 96% vs 97%; P=.72), or PSAF (10-year PSAF, 53% vs 55%; P=.99) between groups. Conclusion LTAD did not confer a benefit in terms of OS, DSS, or PSAF rates in the intermediate-risk subset in this study. Whereas the subset was relatively small, treatment assignment was randomly applied, and a trend in favor of LTAD would have been of interest. Given the small number of disease-specific deaths observed and lack of benefit with respect to our endpoints, this secondary analysis does not suggest that exploration of longer hormonal therapy is worth testing in the intermediate-risk prostate cancer subset. PMID:28126300

68Ga-PSMA-617 PET/CT: a promising new technique for predicting risk stratification and metastatic risk of prostate cancer patients.

PubMed

Liu, Chen; Liu, Teli; Zhang, Ning; Liu, Yiqiang; Li, Nan; Du, Peng; Yang, Yong; Liu, Ming; Gong, Kan; Yang, Xing; Zhu, Hua; Yan, Kun; Yang, Zhi

2018-05-02

The purpose of this study was to investigate the performance of 68 Ga-PSMA-617 PET/CT in predicting risk stratification and metastatic risk of prostate cancer. Fifty newly diagnosed patients with prostate cancer as confirmed by needle biopsy were continuously included, 40 in a train set and ten in a test set. 68 Ga-PSMA-617 PET/CT and clinical data of all patients were retrospectively analyzed. Semi-quantitative analysis of PET images provided maximum standardized uptake (SUVmax) of primary prostate cancer and volumetric parameters including intraprostatic PSMA-derived tumor volume (iPSMA-TV) and intraprostatic total lesion PSMA (iTL-PSMA). According to prostate cancer risk stratification criteria of the NCCN Guideline, all patients were simplified into a low-intermediate risk group or a high-risk group. The semi-quantitative parameters of 68 Ga-PSMA-617 PET/CT were used to establish a univariate logistic regression model for high-risk prostate cancer and its metastatic risk, and to evaluate the diagnostic efficacy of the predictive model. In the train set, 30/40 (75%) patients had high-risk prostate cancer and 10/40 (25%) patients had low-to-moderate-risk prostate cancer; in the test set, 8/10 (80%) patients had high-risk prostate cancer while 2/10 (20%) had low-intermediate risk prostate cancer. The univariate logistic regression model established with SUVmax, iPSMA-TV and iTL-PSMA could all effectively predict high-risk prostate cancer; the AUC of ROC were 0.843, 0.802 and 0.900, respectively. Based on the test set, the sensitivity and specificity of each model were 87.5% and 50% for SUVmax, 62.5% and 100% for iPSMA-TV, and 87.5% and 100% for iTL-PSMA, respectively. The iPSMA-TV and iTL-PSMA-based predictive model could predict the metastatic risk of prostate cancer, the AUC of ROC was 0.863 and 0.848, respectively, but the SUVmax-based prediction model could not predict metastatic risk. Semi-quantitative analysis indexes of 68 Ga-PSMA-617 PET/CT imaging can be used as "imaging biomarkers" to predict risk stratification and metastatic risk of prostate cancer.

The Cancer of the Prostate Risk Assessment (CAPRA) score predicts biochemical recurrence in intermediate-risk prostate cancer treated with external beam radiotherapy (EBRT) dose escalation or low-dose rate (LDR) brachytherapy.

PubMed

Krishnan, Vimal; Delouya, Guila; Bahary, Jean-Paul; Larrivée, Sandra; Taussky, Daniel

2014-12-01

To study the prognostic value of the University of California, San Francisco Cancer of the Prostate Risk Assessment (CAPRA) score to predict biochemical failure (bF) after various doses of external beam radiotherapy (EBRT) and/or permanent seed low-dose rate (LDR) prostate brachytherapy (PB). We retrospectively analysed 345 patients with intermediate-risk prostate cancer, with PSA levels of 10-20 ng/mL and/or Gleason 7 including 244 EBRT patients (70.2-79.2 Gy) and 101 patients treated with LDR PB. The minimum follow-up was 3 years. No patient received primary androgen-deprivation therapy. bF was defined according to the Phoenix definition. Cox regression analysis was used to estimate the differences between CAPRA groups. The overall bF rate was 13% (45/345). The CAPRA score, as a continuous variable, was statistically significant in multivariate analysis for predicting bF (hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.10-1.72, P = 0.006). There was a trend for a lower bF rate in patients treated with LDR PB when compared with those treated by EBRT ≤ 74 Gy (HR 0.234, 95% CI 0.05-1.03, P = 0.055) in multivariate analysis. In the subgroup of patients with a CAPRA score of 3-5, CAPRA remained predictive of bF as a continuous variable (HR 1.51, 95% CI 1.01-2.27, P = 0.047) in multivariate analysis. The CAPRA score is useful for predicting biochemical recurrence in patients treated for intermediate-risk prostate cancer with EBRT or LDR PB. It could help in treatment decisions. © 2013 The Authors. BJU International © 2013 BJU International.

Large institutional variations in use of androgen deprivation therapy with definitive radiotherapy in a population-based cohort of men with intermediate- and high-risk prostate cancer.

PubMed

Ong, Wee Loon; Foroudi, Farshad; Evans, Sue; Millar, Jeremy

2017-11-01

To evaluate the pattern of use of androgen deprivation therapy (ADT) with definitive radiotherapy (RT) in men with prostate cancer (PCa) in a population-based study in Australia. This is a prospective cohort of men with intermediate- and high-risk PCa, captured in the population-based Prostate Cancer Outcome Registry Victoria, who were treated with definitive prostate RT between January 2010 and December 2015. The primary outcome of interest was ADT utilization. Chi-squared test for trend was used to evaluate the temporal trend in the use of ADT over the study period. Multivariate logistic regressions were used to evaluate the effects of patient-, tumour- and treatment-related factors, and treatment institutions (public/ private and metropolitan/ regional) on the likelihood of ADT utilization. A total of 1806 men were included in the study, 199 of whom (11%) had favourable National Comprehensive Cancer Network (NCCN) intermediate-risk disease (i.e. only one intermediate-risk feature, primary Gleason grade 3, and <50% biopsy core involved), 687 (38%) had unfavourable NCCN intermediate-risk disease, and 920 (51%) had high-risk disease. Of the 1806 men, 1155 (64%) received ADT with RT. Men with NCCN high-risk PCa (84%) were more likely to have ADT than men with favourable NCCN intermediate-risk (32%) and unfavourable NCCN intermediate-risk (46%) PCa (P < 0.001). Men treated in public institutions (66%, vs 47% in private institutions; P < 0.001) and regional centres (78%, vs 59% in metropolitan institutions; P < 0.001) were more likely to receive ADT. There was a trend towards an increase in ADT utilization from 50% in 2010 to 64% in 2015 (P < 0.001). In multivariate analyses (adjusting for age, tumour-related factors, year of treatment and use of brachytherapy boost), treatment institution (public and regional) remained independently associated with increased likelihood of ADT utilization. Men with intermediate-risk PCa treated in regional and public institutions were 2.7 times (95% confidence interval [CI] 1.9-3.9; P < 0.001) and 2.8 times (95% CI 1.4-5.3; P = 0.002), more likely to receive ADT with RT, respectively, while men with high-risk PCa treated in regional and public institutions were 3.1 times (95% CI 1.7-5.7; P < 0.001) and 3.0 times (95% CI 1.7-5.4; P < 0.001), more likely to receive ADT with RT, respectively. This is the largest Australasian contemporary series reporting on the pattern of use of ADT with definitive prostate RT. While there was an increasing trend towards use of ADT over time, ADT still appeared to be underutilized in certain groups of patients who may benefit from ADT, with approximately one in five men with high-risk and one in two with unfavourable intermediate-risk PCa not receiving ADT with RT. There was notable variation in the use of ADT between public vs private and metropolitan vs regional institutions. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Effects of Presurgical Treatment for Prostate Cancer

Cancer.gov

In this study, men diagnosed with androgen-sensitive prostate cancer with intermediate- or high-risk features will be examined with mpMRI, undergo targeted biopsies, and be treated with neoadjuvant androgen deprivation therapy.

Timing of Biochemical Failure and Distant Metastasis for Low, Intermediate, and High Risk Prostate Cancer after Radiotherapy

PubMed Central

Morgan, Peter B.; Hanlon, Alexandra L.; Horwitz, Eric M.; Buyyounouski, Mark K.; Uzzo, Robert G.; Pollack, Alan

2007-01-01

Condensed Abstract The timing of biochemical failure and distant metastasis after radiotherapy for low, intermediate and high-risk prostate cancer was determined. The patterns of failure suggest that the majority of early failures were due to subclinical micrometastases present at diagnosis, whereas a late wave of metastasis at 10–12 years in every risk group was consistent with tumor spread from local persistence of disease. Background The relationship of prostate cancer risk group stratification and the timing of biochemical failure (BF) and distant metastasis (DM) is not well defined. We sought to differentiate early failures due to subclinical micrometastasis at presentation from late failures due to local persistence. Methods A total of 1833 men with clinically localized prostate cancer treated with 3D-conformal radiotherapy with or without short-term androgen deprivation were retrospectively analyzed. The interval hazard rates of DM and BF, using ASTRO and Phoenix (Nadir+2) definitions, were determined for men with low, intermediate, and high risk disease. Results Median follow-up was 67 months. Multivariate analysis showed that increasing risk group was independently associated with higher ASTRO BF (P<.0001) and Nadir+2 BF (P<.0001). The preponderance (87%) of ASTRO BF occurred ≤4 years after RT, while Nadir+2 BF was more evenly spread over years 1–12, with 43% at >4 years. The hazard of Nadir+2 BF persisted in years 8–12 in all risk groups. The interval hazard function for DM appeared to be biphasic (early and late peaks) for intermediate and high risk patients, but no distinct early wave was evident for low risk patients. Conclusions ASTRO BF underestimates late BF due to backdating. Local persistence of disease is suggested by delayed Nadir+2 BF and subsequent late DM in every risk group. The paucity of early DM among those with low risk tumors supports the hypothesis that occult micrometastases contributed to the early wave. PMID:17520705

Comparison of semi-extended and standard lymph node dissection in radical prostatectomy: A single-institute experience.

PubMed

Hoshi, Senji; Hayashi, Natuho; Kurota, Yuuta; Hoshi, Kiyotsugu; Muto, Akinori; Sugano, Osamu; Numahata, Kenji; Bilim, Vladimir; Sasagawa, Isoji; Ohta, Shoichiro

2015-09-01

Standard lymphadenectomy for prostate cancer is limited to the obturator lymph nodes (LNs), although the internal and external iliac LNs represent the primary landing zone for prostatic lymphatic drainage. We performed anatomically semi-extended pelvic lymph node dissection (PLND) to assess the incidence of LN metastasis in cases of clinically localized prostate cancer. A total of 730 consecutive patients underwent radical prostatectomy with either semi-extended PLND, comprising 6 selective fields, namely the external iliac, internal iliac and obturator LNs bilaterally, or standard LND (obturator LNs alone). A total of 131 patients undergoing semi-extended PLND were compared with 599 patients undergoing standard LND. The patients were stratified into high-risk [prostate-specific antigen (PSA)>20 ng/ml, Gleason score (GS)≥8], intermediate-risk (PSA 10-20 ng/ml, GS=4+3) and low-risk (PSA<10 ng/ml, GS≤3+4) subgroups. Following semi-extended LND, positive LNs were detected in 12/61 (20%) of the high-risk, 1/30 (3%) of the intermediate-risk and 0/40 (0%) of the low-risk cases. Following standard LND, positive LNs were detected in 13/182 (7%) of the high-risk, 1/164 (0.6%) of the intermediate-risk and 0/253 (0%) of the low-risk cases. In high-risk patients, the detection rate of LN metastasis was significantly higher following extended LND compared with standard LND (P<0.01). In 9 of 13 patients (69%), metastases were identified in the internal and external iliac regions, despite negative obturator LNs. There were no significant differences regarding intraoperative and postoperative complications or blood loss in the two groups. There was no lymphocele formation in patients undergoing either standard or semi-extended LND. Extended pelvic LND (PLND) is associated with a high rate of LN metastasis detection outside the fields of standard LND in cases with clinically localized prostate cancer. Therefore, LND including the internal and external iliac LNs should be performed in all patients with high-risk prostate cancer; however, in the low-risk group, PLND may be omitted.

Outcomes and toxicities in patients with intermediate-risk prostate cancer treated with brachytherapy alone or brachytherapy and supplemental external beam radiation therapy.

PubMed

Schlussel Markovic, Emily; Buckstein, Michael; Stone, Nelson N; Stock, Richard G

2018-05-01

To evaluate the cancer control outcomes and long-term treatment-related morbidity of brachytherapy as well as combination brachytherapy and external beam radiation therapy (EBRT) in patients with intermediate-risk prostate cancer. A retrospective review was conducted in a prospectively collected database of patients with intermediate-risk prostate cancer who were treated either with brachytherapy or brachytherapy and EBRT, with or without androgen deprivation therapy (ADT), in the period 1990-2014. Urinary and erectile dysfunction symptoms were measured using the International Prostate Symptom Score (IPSS), the Mount Sinai erectile function scale and the Sexual Health Inventory for Men (SHIM). Cancer control endpoints included biochemical failure and development of distant metastases. All statistical analyses were carried out using the Statistical Package for Social Science (SPSS). Survival curves were calculated using Kaplan-Meier actuarial methods and compared using log-rank tests. Cox regression multivariate analyses were used to test the effect of multiple variables on treatment outcomes. A total of 902 patients were identified, with a median follow-up of 91 months. Of these, 390 received brachytherapy and 512 received combination therapy with EBRT. In patients with one intermediate-risk factor, the addition of EBRT did not significantly affect freedom from biochemical failure or distant metastases. Among patients with two or three intermediate-risk factors, added EBRT did not improve freedom from biochemical failure. Significant differences in late toxicity between patients treated with brachytherapy vs combination brachytherapy and EBRT were identified including urge incontinence (P < 0.001), haematuria (P < 0.001), dysuria (P < 0.001), and change in quality-of-life IPSS (P = 0.002). These symptoms were reported by patients at any point during treatment follow-up. Analysis of patients who were potent before treatment using actuarial methods showed that patients receiving combination therapy more frequently experienced loss of potency, as measured by the Mount Sinai erectile function scale (P = 0.040). Brachytherapy monotherapy results in equal biochemical and distant control in both patients with one and more than one intermediate-risk features. While no significant benefit was shown, we believe that the addition of EBRT may prevent recurrence in patients with multiple intermediate-risk features and should be considered. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

18F Fluorocholine Dynamic Time-of-Flight PET/MR Imaging in Patients with Newly Diagnosed Intermediate- to High-Risk Prostate Cancer: Initial Clinical-Pathologic Comparisons.

PubMed

Choi, Joon Young; Yang, Jaewon; Noworolski, Susan M; Behr, Spencer; Chang, Albert J; Simko, Jeffry P; Nguyen, Hao G; Carroll, Peter R; Kurhanewicz, John; Seo, Youngho

2017-02-01

Purpose To investigate the initial clinical value of fluorine 18 ( 18 F) fluorocholine (FCH) dynamic positron emission tomography (PET)/magnetic resonance (MR) imaging by comparing its parameters with clinical-pathologic findings in patients with newly diagnosed intermediate- to high-risk prostate cancer (PCa) who plan to undergo radical prostatectomy. Materials and Methods The institutional review board approved the study protocol, and informed written consent was obtained from all subjects for this HIPAA-compliant study. Twelve men (mean age ± standard deviation, 61.7 years ± 8.4; range, 46-74 years) with untreated intermediate- to high-risk PCa characterized according to Cancer of the Prostate Risk Assessment (CAPRA) underwent preoperative FCH dynamic PET/MR imaging followed by radical prostatectomy between April and November 2015. PET/MR imaging parameters including average and maximum K1 (delivery rate constant) and standardized uptake values (SUVs) and Prostate Imaging Reporting and Data System (PI-RADS) version 2 scores were measured and compared with clinical-pathologic characteristics. For statistical analysis, the Spearman rank correlation and Mann-Whitney U tests were performed. Results Of the PET parameters, maximum SUV of primary tumors showed significant correlations with several clinical-pathologic parameters including serum prostate-specific antigen level (ρ = 0.71, P = .01), pathologic stage (ρ = 0.59, P = .043), and postsurgical CAPRA score (ρ = 0.72, P = .008). The overall PI-RADS score showed significant correlations with pathologic tumor volume (ρ = 0.81, P < .001), percentage of tumor cells with Gleason scores greater than 3 (ρ = 0.59, P = .02), and postsurgical CAPRA score (ρ = 0.58, P = .046). The high-risk postsurgical CAPRA score patient group had a significantly higher maximum SUV than did the intermediate-risk group. Combined PET and MR imaging showed improved sensitivity (88%) for prediction of pathologic extraprostatic extension compared with that with MR imaging (50%) and PET (75%) performed separately. Conclusion Maximum SUVs and PI-RADS scores from FCH PET/MR imaging show good correlation with clinical-pathologic characteristics, such as postsurgical CAPRA score, which are related to prognosis in patients with newly diagnosed intermediate- to high-risk PCa. © RSNA, 2016 Online supplemental material is available for this article.

What does postradiotherapy PSA nadir tell us about freedom from PSA failure and progression-free survival in patients with low and intermediate-risk localized prostate cancer?

PubMed

DeWitt, K D; Sandler, H M; Weinberg, V; McLaughlin, P W; Roach, M

2003-09-01

To determine whether the post-external beam radiotherapy (RT) prostate-specific antigen nadir (nPSA) improves our ability to predict freedom from PSA failure, progression-free survival (PFS), and overall survival. Controversy regarding the importance of nPSA after external beam RT as a prognostic indicator for patients with localized prostate cancer has continued. This analysis was based on the data from 748 patients with low and intermediate-risk localized prostate cancer treated with external beam RT alone. Patients were categorized by nPSA quartile groups with cutpoints of less than 0.3, 0.3 to less than 0.6, 0.6 to less than 1.2, and 1.2 ng/mL or greater. Both univariate and multivariate analyses were used to determine the significance of nPSA on PSA failure (American Society for Therapeutic Radiology Oncology consensus definition), PFS (death after PSA failure), and overall survival (death from any cause). Freedom from PSA failure was strongly associated with nadir quartile groups (P <0.0001). PFS was also significantly different statistically among nadir quartile groups (P = 0.02). No statistically significant difference was found in overall survival associated with nPSA at this point. nPSA is a strong independent predictor of freedom from PSA failure and PFS in patients with low and intermediate-risk localized prostate cancer treated with RT alone. Longer follow-up and larger patient numbers are required to confirm these observations.

Urinary functional outcomes and toxicity five years after proton therapy for low- and intermediate-risk prostate cancer: Results of two prospective trials

PubMed Central

2013-01-01

Background. To assess genitourinary (GU) function and toxicity in patients treated with image-guided proton therapy (PT) for early- and intermediate-risk prostate cancer and to analyze the impact of pretreatment urinary obstructive symptoms on urinary function after PT. Material and methods. Two prospective trials accrued 171 prostate cancer patients from August 2006 to September 2007. Low-risk patients received 78 cobalt gray equivalent (CGE) in 39 fractions and intermediate-risk patients received 78–82 CGE. Median follow-up was five years. The International Prostate Symptom Score (IPSS) and GU toxicities (per CTCAE v3.0 and v4.0) were documented prospectively. Results. Five transient GU events were scored Gr 3 per CTCAE v4.0, for a cumulative late GU toxicity rate of 2.9% at five years. There were no Gr 4 or 5 events. On multivariate analysis (MVA), the only factor predictive of Gr 2 + GU toxicity was pretreatment GU symptom management (p = 0.0058). Patients with pretreatment IPSS of 15–25 had a decline (clinical improvement) in median IPSS from 18 before treatment to 10 at their 60-month follow-up. At last follow-up, 18 (54.5%) patients had a > 5-point decline, 14 (42.5%) remained stable, and two patients (3%) had a > 5-point rise (deterioration) in IPSS. Patients with IPSS < 15 had a stable median IPSS of 6 before treatment and at 60 months. Conclusion. Urologic toxicity at five years with image-guided PT has been uncommon and transient. Patients with pretreatment IPSS of < 15 had stable urinary function five years after PT, but patients with 15–25 showed substantial improvement (decline) in median IPSS, a finding not explained by initiation or dose adjustment of alpha blockers. This suggests that PT provides a minimally toxic and effective treatment for low and intermediate prostate cancer patients, including those with significant pretreatment GU dysfunction (IPSS 15–25). PMID:23477359

Toxicity Assessment of Pelvic Intensity-Modulated Radiotherapy With Hypofractionated Simultaneous Integrated Boost to Prostate for Intermediate- and High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCammon, Robert; Rusthoven, Kyle E.; Kavanagh, Brian

Purpose: To evaluate the toxicity of pelvic intensity-modulated radiotherapy (IMRT) with hypofractionated simultaneous integrated boost (SIB) to the prostate for patients with intermediate- to high-risk prostate cancer. Methods and Materials: A retrospective toxicity analysis was performed in 30 consecutive patients treated definitively with pelvic SIB-IMRT, all of whom also received androgen suppression. The IMRT plans were designed to deliver 70 Gy in 28 fractions (2.5 Gy/fraction) to the prostate while simultaneously delivering 50.4 Gy in 28 fractions (1.8 Gy/fraction) to the pelvic lymph nodes. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to scoremore » toxicity. Results: The most common acute Grade 2 events were cystitis (36.7%) and urinary frequency/urgency (26.7%). At a median follow-up of 24 months, late toxicity exceeding Grade 2 in severity was uncommon, with two Grade 3 events and one Grade 4 event. Grade 2 or greater acute bowel toxicity was associated with signficantly greater bowel volume receiving {>=}25 Gy (p = .04); Grade 2 or greater late bowel toxicity was associated with a higher bowel maximal dose (p = .04) and volume receiving {>=}50 Gy (p = .02). Acute or late bladder and rectal toxicity did not correlate with any of the dosimetric parameters examined. Conclusion: Pelvic IMRT with SIB to the prostate was well tolerated in this series, with low rates of Grade 3 or greater acute and late toxicity. SIB-IMRT combines pelvic radiotherapy and hypofractionation to the primary site and offers an accelerated approach to treating intermediate- to high-risk disease. Additional follow-up is necessary to fully define the long-term toxicity after hypofractionated, whole pelvic treatment combined with androgen suppression.« less

68 Ga-PSMA-PET/CT staging prior to definitive radiation treatment for prostate cancer.

PubMed

Hruby, George; Eade, Thomas; Emmett, Louise; Ho, Bao; Hsiao, Ed; Schembri, Geoff; Guo, Linxin; Kwong, Carolyn; Hunter, Julia; Byrne, Keelan; Kneebone, Andrew

2018-04-16

To explore the utility of prostate specific membrane antigen (PSMA)-positron emission tomography (PET)/computed tomography (CT) in addition to conventional imaging prior to definitive external beam radiation treatment (EBRT) for prostate cancer. All men undergoing PSMA-PET/CT prior to definitive EBRT for intermediate and high-risk prostate cancer were included in our ethics approved prospective database. For each patient, clinical and pathological results, in addition to scan results including site of PSMA positive disease and number of lesions, were recorded. Results of conventional imaging (bone scan, CT and multiparametric magnetic resonance imaging [MRI]) were reviewed and included. One hundred nine men underwent staging PSMA-PET/CT between May 2015 and June 2017; all patients had national comprehensive cancer network (NCCN) intermediate or high-risk prostate cancer and 87% had Gleason score (GS) 4 + 3 or higher. There was positive uptake corresponding to the primary in 108, equivocal in one. All patients with image detected nodal or bony lesions had GS 4 + 3 or more disease. Compared to conventional imaging with bone scan, CT and multiparametric MRI, PSMA-PET/CT upstaged an additional 7 patients (6.4%) from M0 to M1, 16 from N0M0 to N1M0 (14.7%) and downstaged 3 (2.8%) from M1 to M0 disease. PSMA-PET/CT identified the primary in 99% of patients, and altered staging in 21% of men with intermediate or high-risk prostate cancer referred for definitive EBRT compared to CT, bone scan and multiparametric MRI. Following this audit, we recommend the routine use of PSMA-PET/CT prior to EBRT in this patient group. © 2018 John Wiley & Sons Australia, Ltd.

Primary Gleason Grade 4 Impact on Biochemical Recurrence After Permanent Interstitial Brachytherapy in Japanese Patients With Low- or Intermediate-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uesugi, Tatsuya; Saika, Takashi, E-mail: saika@cc.okayama-u.ac.jp; Edamura, Kohei

2012-02-01

Purpose: To reveal a predictive factor for biochemical recurrence (BCR) after permanent prostate brachytherapy (PPB) using iodine-125 seed implantation in patients with localized prostate cancer classified as low or intermediate risk based on National Comprehensive Cancer Network (NCCN) guidelines. Methods and Materials: From January 2004 to December 2009, 414 consecutive Japanese patients with clinically localized prostate cancer classified as low or intermediate risk based on the NCCN guidelines were treated with PPB. The clinical factors including pathological data reviewed by a central pathologist and follow-up data were prospectively collected. Kaplan-Meier and Cox regression analyses were used to assess the factorsmore » associated with BCR. Results: Median follow-up was 36.5 months. The 2-, 3-, 4-, and 5-year BCR-free rates using the Phoenix definition were 98.3%, 96.0%, 91.6%, and 87.0%, respectively. On univariate analysis, the Gleason score, especially primary Gleason grade 4 in biopsy specimens, was a strong predicting factor (p < 0.0001), while age, initial prostate-specific antigen (PSA) level, T stage, and minimal dose delivered to 90% of the prostate volume (D90) were insignificant. Multivariate analysis indicated that a primary Gleason grade 4 was the most powerful prognostic factor associated with BCR (hazard ratio = 6.576, 95% confidence interval, 2.597-16.468, p < 0.0001). Conclusions: A primary Gleason grade 4 carried a worse BCR prognosis than the primary grade 3 in patients treated with PPB. Therefore, the indication for PPB in patients with a Gleason sum of 4 + 3 deserves careful and thoughtful consideration.« less

Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry.

PubMed

Biggs, Colleen N; Siddiqui, Khurram M; Al-Zahrani, Ali A; Pardhan, Siddika; Brett, Sabine I; Guo, Qiu Q; Yang, Jun; Wolf, Philipp; Power, Nicholas E; Durfee, Paul N; MacMillan, Connor D; Townson, Jason L; Brinker, Jeffrey C; Fleshner, Neil E; Izawa, Jonathan I; Chambers, Ann F; Chin, Joseph L; Leong, Hon S

2016-02-23

Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/µL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.

Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry

PubMed Central

Al-Zahrani, Ali A.; Pardhan, Siddika; Brett, Sabine I.; Guo, Qiu Q.; Yang, Jun; Wolf, Philipp; Power, Nicholas E.; Durfee, Paul N.; MacMillan, Connor D.; Townson, Jason L.; Brinker, Jeffrey C.; Fleshner, Neil E.; Izawa, Jonathan I.; Chambers, Ann F.; Chin, Joseph L.; Leong, Hon S.

2016-01-01

Background Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Patients and Methods Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/μL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. Results PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. Conclusions PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer. PMID:26814433

Temporal Trends and the Impact of Race, Insurance, and Socioeconomic Status in the Management of Localized Prostate Cancer.

PubMed

Gray, Phillip J; Lin, Chun Chieh; Cooperberg, Matthew R; Jemal, Ahmedin; Efstathiou, Jason A

2017-05-01

Numerous management options exist for patients with prostate cancer; however, recent trends and their influencing factors are not well described. To describe modern patterns of care and factors associated with management choice using the National Cancer Database. Patients with localized prostate cancer diagnosed between 2004 and 2012 were included and grouped according to National Comprehensive Cancer Network guidelines into low, intermediate, or high risk. Trend analyses and multivariate logistic regression was used to identify factors associated with management. There were 598 640 patients who met the study criteria; 36.3% were classified as low risk, 43.8% intermediate risk, and 20.0% high risk. Over the study period, among low-risk patients, observation increased from 9.2% to 21.3%, while radical prostatectomy (RP) increased from 29.5% to 51.1% (p<0.001 for both). In contrast, external beam radiotherapy decreased from 24.3% to 14.5%, while brachytherapy decreased from 31.7% to 11.1%. A similar pattern was seen for patients with intermediate-risk or high-risk disease. Among high-risk patients, RP increased from 25.1% to 43.4% replacing external beam radiotherapy as the dominant therapy. On multivariate analysis, racial minorities, the uninsured, and low-income patients were less likely to receive RP. Low-risk patients in similar subgroups were significantly more likely to be observed. Limitations include potential miscoding or misclassification of variables. Patterns of care in localized prostate cancer are changing rapidly. While use of observation is increasing in low-risk groups, the use of RP is increasing across all risk groups with a concomitant decline in use of radiotherapy. Socioeconomic factors appear to influence management choice. In this report we identify a recent significant increase in the use of radical prostatectomy for prostate cancer patients. Socioeconomic factors such as race, insurance type, and income may affect treatments offered to and received by patients. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

High intensity focused ultrasound (HIFU).

PubMed

Barkin, Jack

2011-04-01

Curative treatments for localized prostate cancer, from least invasive to most invasive, include brachytherapy, cryosurgery, three-dimensional conformal radiation therapy, external beam radiation therapy, and radical prostatectomy. A patient with localized, low risk or intermediate risk prostate cancer who is diagnosed at an early age and receives one of these treatments has only an approximately 50% chance of maintaining an undetectable prostate-specific antigen (PSA) level, good spontaneous erections, and total continence by 5 years after treatment. This article discusses transrectal high intensity focused ultrasound (HIFU) treatment of localized prostate cancer using the Sonablate 500 (Focus Surgery, Indianapolis, IN, USA) device, which the author has adopted in favor of the Ablatherm (EDAP, TMS S. A., Lyons, France) device, the other HIFU device approved for use in Canada. Characteristics of the ideal prostate cancer include stage T1-T2b, less than 40 cc in size, and with an anterior-posterior dimension of up to 35 mm high. The anterior zone of the prostate is treated before the posterior zone. The procedure involves 2 to 3 second bursts of ultrasound energy, followed by 3 second cooling cycles. In each treatment lesion, the physician achieves a temperature of 100 C at the focal point. The device allows for real-time visualization of tissue response following the delivery of ultrasound energy. HIFU is a minimally invasive, outpatient treatment for localized prostate cancer that provides similar short term and medium term cure rates and considerably less morbidity and side effects than other treatments. Although the effectiveness of HIFU has not yet been demonstrated in large, long term studies, this treatment option should be discussed with patients who have just been diagnosed with low risk or intermediate risk prostate cancer and desire aggressive, noninvasive, curative therapy, with potentially a lower incidence of side effects compared to conventional therapy.

High-intensity focused ultrasound (HIFU) in prostate cancer: a single centre experience in patients with low, intermediate or high-risk of progression.

PubMed

Callea, Andrea; Piccinni, Roberto; Zizzi, Vito; Sblendorio, Domenico; Berardi, Bartolomeo; Tempesta, Antonio; Gala, Francesco Giuseppe; Traficante, Antonio

2010-12-01

High-intensity focused ultrasound (HIFU) is a minimally invasive treatment based on thermal ablation of tissues which are warmed up to 85 degrees C in the focal area. Clinical studies have shown such treatment modality to be safe and effective in the management of localised prostate cancer as well as of local recurrences after radical prostatectomy or radiotherapy. From May 2002 to June 2010, 171 patients with no previous treatment for prostate cancer, aged 44 to 86 years (mean 74.7) underwent 197 HIFU treatments; 22 patients needed a second treatment as the first was incomplete (4 patients) or because of recurrence (18 patients). The prognosis subgroups were defined as low-risk in 29 patients (clinical stage T1-T2a, PSA < or = 10 ng/mL and Gleason score lower than 7), intermediate-risk in 47 patients (clinical stage T2b or PSA 10 - 20 ng/mL or Gleason score of 7), and high-risk in 95 patients (clinical stage > or = T2c or PSA > 20 ng/mL or Gleason score higher than 7). At a mean follow-up of 67.9 months, biochemical success rate (PSA constantly < 0.5 ng/ml) was obtained in 84.2% of low and intermediate risk patients and in 43.1% of high risk patients; post-treatment biopsies (6 months after treatment) revealed no residual tumour in 93.4% of low or intermediate risk patients and in 63.1% of high risk patients. Radical prostatectomy remains the "gold standard" for localised prostate cancer. However, HIFU seems to be a promising alternative and less invasive treatment modality with an encouraging success rate, at least in the short-term, in patients with low and medium risk of progression, not candidates for radical surgery; in cancers with clinical stage > or = T2c, or PSA > 20 ng/mL, or Gleason score higher than 7 seems to get good results in about half of patients.

Primary focal prostate radiotherapy: Do all patients really need whole-prostate irradiation?

PubMed

Jereczek-Fossa, Barbara Alicja; Ciardo, Delia; Petralia, Giuseppe; Bellomi, Massimo; De Bari, Berardino; De Cobelli, Ottavio; Orecchia, Roberto

2016-09-01

To review the available data about focal primary partial prostate irradiation (focal radiotherapy, FRT) for early prostate cancer. Medline search for English language full paper on primary FRT for early prostate cancer including review articles, planning studies or patient series (clinical outcome available) published before May 31, 2015. 22 papers have been found: 11 review articles, 4 planning studies and 7 patient series. Eleven review articles were dedicated to all types of focal therapy including FRT and 2 to FRT only. All planning studies included brachytherapy and showed excellent organ-at-risk sparing. Patient series included together 715 patients (99% treated with brachytherapy) and showed promising tumour control in low-risk cancer. In intermediate-risk tumours, FRT might be suboptimal. Primary FRT is feasible in early prostate cancer. As any other focal therapy, FRT remains investigational until numerous questions are answered. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of primary androgen deprivation therapy in prostate cancer patients using the J-CAPRA risk score

PubMed Central

Akaza, Hideyuki; Hinotsu, Shiro; Usami, Michiyuki; Ogawa, Osamu; Kitamura, Tadaichi; Suzuki, Kazuhiro; Tsukamoto, Taiji; Naito, Seiji; Namiki, Mikio; Hirao, Yoshihiko; Murai, Masaru

2013-01-01

Purpose: To determine the influence of maximal androgen blockade (MAB) and non-MAB hormonal therapy with an luteinizing hormone releasing hormone (LHRH) analog on overall survival of prostate cancer patients in the Japan Study Group of Prostate Cancer (J-CaP) registry according to risk, as assessed using the novel J-CAPRA risk instrument. To undertake a multivariate analysis combining J-CAPRA risk score, type of hormonal therapy and comorbidities, in order to assess their impact on overall survival. Methods: The J-CaP database includes men in Japan diagnosed with any stage of prostate cancer between 2001 and 2003 and treated with primary androgen deprivation therapy (PADT), as monotherapy or in combination. A total of 26,272 men were enrolled and of these 19,265 were treated with PADT. This analysis was undertaken using the latest data set (30 April, 2010) including a total of 15,727 patients who received PADT and had follow-up data for periods ranging from 0 to 9.2 years. Results: MAB for prostate cancer patients with intermediate- or high-risk disease has a significant benefit in terms of overall survival compared with LHRH analog monotherapy or surgical castration alone. Better results may be achieved in older (≥75 years) patients. Patient comorbidities are an important factor in determining overall survival, notably in older patients, and should be considered when selecting therapy. Conclusions: Based on large-scale registry data, this report is the first to analyze the outcomes of MAB therapy in patients with prostate cancer at a wide range of disease stages. MAB therapy may provide significant survival benefits in intermediate- and high-risk patients. PMID:24223407

The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study.

PubMed

Gnanapragasam, V J; Bratt, O; Muir, K; Lee, L S; Huang, H H; Stattin, P; Lophatananon, A

2018-02-28

The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer. We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality. The PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p < 0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current three-tiered system (concordance index (C-index) 0.81 vs. 0.77, p < 0.0001). This superiority was maintained for every age group division (p < 0.0001). Also in the ethnically different Singapore cohort of 2550 men with 142 prostate cancer deaths, the CPG model outperformed the three strata categories (C-index 0.79 vs. 0.76, p < 0.0001). The model also retained superior prognostic discrimination in the treatment sub-groups: radical prostatectomy (n = 20,586), C-index 0.77 vs. 074; radiotherapy (n = 11,872), C-index 0.73 vs. 0.69; and conservative management (n = 14,950), C-index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate-risk (CPG2 vs. CPG3) and high-risk categories (CPG4 vs. CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p < 0.0001). This validation study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.

A New Method for Synthesizing Radiation Dose-Response Data From Multiple Trials Applied to Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diez, Patricia; Vogelius, Ivan S.; Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792

2010-07-15

Purpose: A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high). Methods and Materials: Nine published prostate cancer dose escalation studies including 6,539 patients were identified in the MEDLINE and CINAHL databases and reviewed to assess the relationship between dose and biochemical control. A novel method of analysis is presented in which the normalized dose-response gradient, {gamma}{sub 50}, is estimated for each study and subsequently synthesized across studies. Our method does not assume that biochemical control rates are directly comparable between studies.more » Results: Nonrandomized studies produced a statistically significantly higher {gamma}{sub 50} than randomized studies for intermediate- to high-risk patients ({gamma}{sub 50} = 1.63 vs. {gamma}{sub 50} = 0.93, p = 0.03) and a borderline significantly higher ({gamma}{sub 50} = 1.78 vs. {gamma}{sub 50} = 0.56, p = 0.08) for low-risk patients. No statistically significant difference in {gamma}{sub 50} was found between low- and intermediate- to high-risk patients (p = 0.31). From the pooled data of low and intermediate- to high-risk patients in randomized trials, we obtain the overall best estimate of {gamma}{sub 50} = 0.84 with 95% confidence interval 0.54-1.15. Conclusions: Nonrandomized studies overestimate the steepness of the dose-response curve as compared with randomized trials. This is probably the result of stage migration, improved treatment techniques, and a shorter follow-up in higher dose patients that were typically entered more recently. This overestimation leads to inflated expectations regarding the benefit from dose-escalation and could lead to underpowered clinical trials. There is no evidence of a steeper dose response for intermediate- to high-risk compared with low-risk patients.« less

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kotecha, Rupesh; Djemil, Toufik; Tendulkar, Rahul D.

Purpose: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Methods and Materials: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the targetmore » volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. Results: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. Conclusions: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.« less

Prostate cancer in senior adults: over- or undertreated?

PubMed

Berger, Ingrid; Böhmer, Franz; Ponholzer, Anton; Madersbacher, Stephan

2009-01-01

Despite the widespread use of prostate specific antigen for early prostate cancer (PCa) detection in younger men, PCa is still as disease of the elderly as 2/3 of incident cases are detected in men older than 65 years and 25% are older than 75 years at diagnosis. Opportunistic screening for PCa is not recommended for men with a life expectancy of less than 10 years. The therapeutic strategy for senior adults is driven by tumour stage/aggressiveness, co-morbidity and chronological age. Elderly patients with low/intermediate risk tumours - particularly those with a life expectancy of less than 10 years - are best managed by watchful waiting. Senior adults with intermediate/high risk tumours and a life expectancy of >10 years may benefit from curative local therapy such as radical prostatectomy or combined external beam irradiation/androgen ablation therapy. For elderly patients with metastatic disease, androgen deprivation remains the mainstay of therapy, intermittent androgen ablation is a promising approach.

Active Surveillance for Low and Intermediate Risk Prostate Cancer: Opinions of North American Genitourinary Oncology Expert Radiation Oncologists.

PubMed

McClelland, Shearwood; Sandler, Kiri A; Degnin, Catherine; Chen, Yiyi; Mitin, Timur

2018-04-01

The ProtecT trial has provided level 1 evidence supporting active surveillance for prostate cancer patients with low-risk and intermediate-risk disease. The effect of these findings on the opinions of North American genitourinary (GU) experts regarding the role of active surveillance for these patients has not been previously examined. A survey was distributed to 88 practicing North American GU physicians serving on decision-making committees of cooperative group research organizations. Questions pertained to appropriateness of active surveillance in patients with low-risk and intermediate-risk (Gleason 3+4) disease. Opinions regarding active surveillance were correlated with practice patterns using Fisher exact test. Forty-two radiation oncologists completed the survey. Forty percent had been in practice for more than 20 years; 90% practice at an academic center. Forty-five percent see ≥ 20 patients per month in consultation. More than 95% (40 of 42) recommended active surveillance for Gleason 6 disease, whereas only 17% recommended active surveillance for Gleason 3+4 disease. There were no demographic differences between supporters or opponents regarding active surveillance with regard to monthly patient volume, practice type, likelihood of self-identifying as an expert brachytherapist, belief in advanced imaging techniques, or preferred default external beam radiation therapy dose/fractionation for either low-risk or intermediate-risk disease. However, there was a trend toward greater support of active surveillance for Gleason 3+4 disease among experts having practiced < 10 years versus ≥ 10 years (P = .085). Active surveillance is almost universally supported by North American GU expert radiation oncologists for low-risk prostate cancer. However, there is very weak support for this strategy in Gleason 3+4 disease despite the ProtecT trial providing level 1 evidentiary support in both risk groups. There were no significant differences between experts supporting versus opposing active surveillance for either low-risk or intermediate-risk disease. These preferences might affect the design of future clinical studies, influencing the adoption of active surveillance in North American clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Prostate Cancer Severity on Functional Outcomes After Localized Treatment: Comparative Effectiveness Analysis of Surgery and Radiation Study Results.

PubMed

Tyson, Mark Douglas; Koyama, Tatsuki; Lee, Dan; Hoffman, Karen E; Resnick, Matthew J; Wu, Xiao-Cheng; Cooperberg, Matthew R; Goodman, Michael; Greenfield, Sheldon; Hamilton, Ann S; Hashibe, Mia; Paddock, Lisa E; Stroup, Antoinette; Chen, Vivien; Conwill, Ralph; McCollum, Dan; Penson, David F; Barocas, Daniel A

2018-07-01

Whether prostate cancer severity modifies patient-reported functional outcomes after radical prostatectomy (RP) or external beam radiotherapy (EBRT) for localized cancer is unknown. The purpose of this study was to determine whether differences in predicted function over time between RP and EBRT varied by risk group. The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, observational study that enrolled men with localized prostate cancer in 2011-2012. Among 2117 CEASAR participants who underwent RP or EBRT, 817 had low-risk, 902 intermediate-risk, and 398 high-risk disease. Patient-reported, disease-specific function was measured using the 26-item Expanded Prostate Index Composite (at baseline and 6, 12, and 36 mo). Predicted function was estimated using regression models and compared by disease risk. Low-risk EBRT patients reported 3-yr sexual function scores 12 points higher than those of low-risk RP patients (RP, 39 points [95% confidence interval {CI}, 37-42] vs EBRT, 52 points [95% CI, 47-56]; p<0.001). The difference in 3-yr scores for high-risk patients was not clinically significant (RP, 32 points [95% CI, 28-35] vs EBRT, 38 points [95% CI, 33-42]; p=0.03). However, when using a commonly used binary definition of sexual function (erections firm enough for intercourse), no major differences were noted between RP and EBRT at 3 yr across low-, intermediate-, and high-risk disease strata. No clinically significant interactive effects between treatment and cancer severity were observed for incontinence, bowel, irritative voiding, and hormone domains. The primary limitation is the lack of firmly established thresholds for clinically significant differences in Expanded Prostate Index Composite domain scores. For men with low-risk prostate cancer, EBRT was associated with higher sexual function scores at 3 yr than RP; however, for men with high-risk prostate cancer, no clinically significant difference was noted. Men with high-risk prostate cancer should be counseled that EBRT and RP carry similar sexual function outcomes at 3 yr. In this report, we studied the urinary, sexual, bowel, and hormonal functions of patients 3 yr after undergoing prostate cancer surgery or radiation. We found that for patients with high-risk disease, sexual function was similar between surgery and radiation. We conclude that high-risk patients undergoing radiation therapy should be counseled that sexual function may not be as good as low-risk patients undergoing radiation. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Advances in prostate-specific membrane antigen PET of prostate cancer.

PubMed

Bouchelouche, Kirsten; Choyke, Peter L

2018-05-01

In recent years, a large number of reports have been published on prostate-specific membrane antigen (PSMA)/PET in prostate cancer (PCa). This review highlights advances in PSMA PET in PCa during the past year. PSMA PET/computed tomography (CT) is useful in detection of biochemical recurrence, especially at low prostate-specific antigen (PSA) values. The detection rate of PSMA PET is influenced by PSA level. For primary PCa, PSMA PET/CT shows promise for tumour localization in the prostate, especially in combination with multiparametric MRI (mpMRI). For primary staging, PSMA PET/CT can be used in intermediate and high-risk PCa. Intraoperative PSMA radioligand guidance seems promising for detection of malignant lymph nodes. While the use of PSMA PET/MRI in primary localized disease is limited to high and intermediate-risk patients and localized staging, in the recurrence setting, PET/MRI can be particularly helpful when the lesions are subtle. PSMA PET/CT is superior to choline PET/CT and other conventional imaging modalities. Molecular imaging with PSMA PET continues to pave the way for personalized medicine in PCa.However, large prospective clinical studies are still needed to fully evaluate the role of PSMA PET/CT and PET/MRI in the clinical workflow of PCa.

High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edelman, Scott; Liauw, Stanley L.; Rossi, Peter J.

2012-08-01

Purpose: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Methods and Materials: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as {>=}T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: {>=}T3, prostate-specific antigen level >20 ng/mL, GS {>=}8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADTmore » and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. Results: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Conclusions: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy-related GI or GU toxicity.« less

Long-term outcomes of open radical retropubic prostatectomy for clinically localized prostate cancer in the prostate-specific antigen era.

PubMed

Dorin, Ryan P; Daneshmand, Siamak; Lassoff, Mark A; Cai, Jie; Skinner, Donald G; Lieskovsky, Gary

2012-03-01

To determine long-term oncological outcomes and complication rates for patients with clinically organ confined prostate adenocarcinoma (PCa) treated with open radical retropubic prostatectomy and pelvic lymph node dissection (RRP/PLND) in the prostate-specific antigen (PSA) era. Outcomes data were obtained from a prospectively maintained prostate cancer database. Patients with cT1/cT2 PCa undergoing RRP/PLND without neoadjuvant therapy between July 1988 and June 2008 were included. Kaplan-Meier and Cox proportional regression models were used to evaluate factors influencing biochemical recurrence, clinical recurrence, and overall survival (OS). A total of 2487 patients met inclusion criteria, and median follow-up was 7.2 years (range 1-21 years). Of the patients, 49.7% were low risk, 33.2% intermediate risk, and 16.1% high risk by D'Amico criteria, and 6% were LN+. The 10-year biochemical recurrence-free survival (BCRFS) for low-, intermediate-, and high-risk patients was 92%, 83%, and 76%, respectively (P < .001), and 10 year OS was 91%, 83%, and 74%, respectively (P < .001). BCRFS at 10 years was 76% and 88% for patients with positive and negative margins, respectively (P < .001). Of the 2487 patients, 11% developed BCR, and 3.7% experienced CR, with 9 local recurrences. The overall complication rate was 2.3%, and the cancer specific mortality rate was 2%. D'Amico risk group, margin status, and LN status are significantly correlated with outcomes in patients undergoing RRP/PLND for clinically localized PCa. Local recurrence and death from prostate cancer are rare in patients undergoing open RRP/PLND for clinically organ confined disease in the PSA era. Copyright © 2012 Elsevier Inc. All rights reserved.

Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer--a large nested case-control study within the JANUS cohort in Norway.

PubMed

de Vogel, Stefan; Ulvik, Arve; Meyer, Klaus; Ueland, Per Magne; Nygård, Ottar; Vollset, Stein Emil; Tell, Grethe S; Gregory, Jesse F; Tretli, Steinar; Bjørge, Tone

2014-01-01

Methyl group donors and intermediates of one-carbon metabolism affect DNA synthesis and DNA methylation, and may thereby affect prostate carcinogenesis. Choline, the precursor of betaine, and the one-carbon metabolite sarcosine have been associated with increased prostate cancer risk. Within JANUS, a prospective cohort in Norway (n = 317,000) with baseline serum samples, we conducted a nested case-control study among 3,000 prostate cancer cases and 3,000 controls. Using conditional logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer risk were estimated according to quintiles of circulating betaine, dimethylglycine (DMG), sarcosine, glycine and serine. High sarcosine and glycine concentrations were associated with reduced prostate cancer risk of borderline significance (sarcosine: highest vs. lowest quintile OR = 0.86, CI = 0.72-1.01, p(trend) = 0.03; glycine: OR = 0.83, CI = 0.70-1.00, p(trend) = 0.07). Serum betaine, DMG and serine were not associated with prostate cancer risk. However, individuals with a high glycine/serine ratio were at decreased prostate cancer risk (OR = 0.74, CI = 0.69-0.85, p(trend) < 0.001). This population-based study suggested that men with high serum sarcosine or glycine concentrations have modestly reduced prostate cancer risk. Ratios of metabolites reflecting one-carbon balance may be associated with prostate cancer risk, as demonstrated for the glycine/serine ratio, and should be explored in future studies. © 2013 UICC.

Active Surveillance of Prostate Cancer: Use, Outcomes, Imaging, and Diagnostic Tools

PubMed Central

Tosoian, Jeffrey J; Loeb, Stacy; Epstein, Jonathan I; Turkbey, Baris; Choyke, Peter; Schaeffer, Edward M

2016-01-01

Active surveillance (AS) has emerged as a standard management option for men with very low-risk and low-risk prostate cancer, and contemporary data indicate that use of AS is increasing in the United States and abroad. In the favorable-risk population, reports from multiple prospective cohorts indicate a less than 1% likelihood of metastatic disease and prostate cancer-specific mortality over intermediate-term follow-up (median 5 to 6 years). Higher-risk men participating in AS appear to be at increased risk of adverse outcomes, but these populations have not been adequately studied to this point. Although monitoring on AS largely relies on serial prostate biopsy, a procedure associated with significant morbidity, there is a need for improved diagnostic tools for patient selection and monitoring. Revisions from the 2014 International Society of Urologic Pathology consensus conference have yielded a more intuitive reporting system and detailed reporting of low-intermediate grade tumors, which should facilitate the practice of AS. Meanwhile, emerging modalities such as multiparametric magnetic resonance imaging and tissue-based molecular testing have shown prognostic value in some populations. At this time, however, these instruments have not been sufficiently studied to consider their routine, standardized use in the AS setting. Future studies should seek to identify those platforms most informative in the AS population and propose a strategy by which promising diagnostic tools can be safely and efficiently incorporated into clinical practice. PMID:27249729

SU-E-T-434: Fixed Margin Or Online Adaptation for Intermediate-Risk Prostate Stereotactic Body Radiation Therapy? A Dosimetric Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheng, Y; Li, T; Yin, F

2015-06-15

Purpose: To investigate the choice of fixed margin or online adaptation when treating intermediate-risk prostate cancer including seminal vesicles (SV) using stereotactic body radiation therapy (SBRT). Methods: 9 prostate SBRT patients were retrospectively studied. All patients were implanted with fiducial markers in the prostate for daily localization and verification. Each patient had 5 pairs of pre-treatment and post-treatment cone-beam CT (CBCT) per protocol. SVs were contoured on planning CT and all CBCTs by one attending physician. Simultaneous integral boost (SIB) IMRT plans were developed to deliver 25Gy/5fx to the SV while delivering 37Gy/5fx to the prostate. A 3mm isotropic marginmore » was added to the prostate while a 5 mm isotropic margin was used for the SV. The planning CT was registered to daily pre-treatment and post-treatment CBCT based on fiducial markers in the prostate to mimic online prostate localization; and the SV on daily CBCT was transferred to the CT structure set after the prostates were aligned. Daily pre-treatment and post-treatment SV dose coverage and the organ-at-risk (OAR) sparing were evaluated for the SIB regimen. At least 95% of the SV need to receive the prescription dose (5Gy per fraction). Results: For the total of 90 daily SVs analyzed (ten CBCTs for each of nine patients), only 45 daily SVs (50%) were able to meet the coverage that 95% of the SV received 25Gy. The OAR sparing performance was acceptable for most of the dosimetric constraints in low-risk prostate SBRT protocol with only two exceptions in bladder V100 (cc). Conclusion: A fixed 5mm margin for SV is not sufficient to provide consistent daily dose coverage due to SV’s substantial inter- and intra-fractional motion relative to the prostate. This finding calls for innovative strategies in margin design as well as online treatment adaptation. This work is partially supported a master research grant from Varian Medical Systems.« less

Diagnostic Accuracy of 64Copper Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Primary Lymph Node Staging of Intermediate- to High-risk Prostate Cancer: Our Preliminary Experience.

PubMed

Cantiello, Francesco; Gangemi, Vincenzo; Cascini, Giuseppe Lucio; Calabria, Ferdinando; Moschini, Marco; Ferro, Matteo; Musi, Gennaro; Butticè, Salvatore; Salonia, Andrea; Briganti, Alberto; Damiano, Rocco

2017-08-01

To assess the diagnostic accuracy of 64 Copper prostate-specific membrane antigen ( 64 Cu-PSMA) positron emission tomography/computed tomography (PET/CT) in the primary lymph node (LN) staging of a selected cohort of intermediate- to high-risk prostate cancer (PCa) patients. An observational prospective study was performed in 23 patients with intermediate- to high-risk PCa, who underwent 64 Cu-PSMA PET/CT for local and lymph nodal staging before laparoscopic radical prostatectomy with an extended pelvic LN dissection. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for LN status of 64 Cu-PSMA PET/CT were calculated using the final pathological findings as reference. Furthermore, we evaluated the correlation of intraprostatic tumor extent and grading with 64 Cu-PSMA intraprostatic distribution. Pathological analysis of LN involvement in 413 LNs harvested from our study cohort identified a total of 22 LN metastases in 8 (5%) of the 23 (35%) PCa patients. Imaging-based LN staging in a per-patient analysis showed that 64 Cu-PSMA PET/CT was positive in 7 of 8 LN-positive patients (22%) with a sensitivity of 87.5%, specificity of 100%, PPV of 100%, and NPV of 93.7%, considering the maximum standardized uptake value (SUV max ) at 4 hours as our reference. Receiver operating characteristic curve was characterized by an area under the curve of 0.938. A significant positive association was observed between SUV max at 4 hours with Gleason score, index, and cumulative tumor volume. In our intermediate- to high-risk PCa patients study cohort, we showed the high diagnostic accuracy of 64 Cu-PSMA PET/CT for primary LN staging before radical prostatectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

Dose constraints for moderate hypofractionated radiotherapy for prostate cancer: The French genito-urinary group (GETUG) recommendations.

PubMed

Langrand-Escure, J; de Crevoisier, R; Llagostera, C; Créhange, G; Delaroche, G; Lafond, C; Bonin, C; Bideault, F; Sargos, P; Belhomme, S; Pasquier, D; Latorzeff, I; Supiot, S; Hennequin, C

2018-04-01

Considering recent phase III trials results, moderate hypofractionated radiotherapy can be considered as a standard treatment for low and intermediate risk prostate cancer management. This assessment call for a framework allowing homogeneous and reproducible practices in the different centers using this radiotherapy schedule. The French Genito-Urinary Group (GETUG) provides here recommendations for daily practice of moderate hypofractionated radiotherapy for prostate cancer, with indications, dose, fractionation, pre-treatment planning, volume of interest delineation (target volume and organs at risk) and margins, dose constraints and radiotherapy techniques. Copyright © 2018. Published by Elsevier SAS.

Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshioka, Yasuo, E-mail: yoshioka@radonc.med.osaka-u.ac.jp; Kotsuma, Tadayuki; Komiya, Akira

Purpose: To present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer. Methods and Materials: From 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27 Gy/2 fractions for 69 patients (13%), 45.5 Gy/7 fractions for 168 (32%), 49 Gy/7 fractions for 149 (28%), 54 Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivationmore » therapy, and 202 patients (39%) did receive androgen deprivation therapy <1 year, 112 (21%) for 1-3 years, and 54 (10%) for >3 years. Median follow-up time was 5.9 years (range, 0.4-18.1 years), with a minimum of 2 years for surviving patients. Results: After 5 years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5 years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected. Conclusions: The findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.« less

External beam radiation therapy for clinically localized prostate cancer: when and how we optimize with concurrent hormonal deprivation.

PubMed

Koontz, Bridget F; Lee, W Robert

2011-10-01

Androgen deprivation plays a major role in the treatment of prostate cancer.Preclinical studies have shown that androgen deprivation provides both an independent cytotoxic effect and radiosensitization on prostate tumors. For men with non-metastatic prostate cancer, the addition of androgen deprivation to radiotherapy has been shown to improve survival for intermediate and high risk disease compared to radiation alone.This review discusses the clinical trial data regarding combination of androgen deprivation and radiation and provides recommendations for its use in men undergoing radiotherapy for localized prostate cancer.

Focal Laser Ablation of Prostate Cancer: Feasibility of Magnetic Resonance Imaging-Ultrasound Fusion for Guidance.

PubMed

Natarajan, Shyam; Jones, Tonye A; Priester, Alan M; Geoghegan, Rory; Lieu, Patricia; Delfin, Merdie; Felker, Ely; Margolis, Daniel J A; Sisk, Anthony; Pantuck, Allan; Grundfest, Warren; Marks, Leonard S

2017-10-01

Focal laser ablation is a potential treatment in some men with prostate cancer. Currently focal laser ablation is performed by radiologists in a magnetic resonance imaging unit (in bore). We evaluated the safety and feasibility of performing focal laser ablation in a urology clinic (out of bore) using magnetic resonance imaging-ultrasound fusion for guidance. A total of 11 men with intermediate risk prostate cancer were enrolled in this prospective, institutional review board approved pilot study. Magnetic resonance imaging-ultrasound fusion was used to guide laser fibers transrectally into regions of interest harboring intermediate risk prostate cancer. Thermal probes were inserted for real-time monitoring of intraprostatic temperatures during laser activation. Multiparametric magnetic resonance imaging (3 Tesla) was done immediately after treatment and at 6 months along with comprehensive fusion biopsy. Ten of 11 patients were successfully treated while under local anesthesia. Mean procedure time was 95 minutes (range 71 to 105). Posttreatment magnetic resonance imaging revealed a confined zone of nonperfusion in all 10 men. Mean zone volume was 4.3 cc (range 2.1 to 6.0). No CTCAE grade 3 or greater adverse events developed and no changes were observed in urinary or sexual function. At 6 months magnetic resonance imaging-ultrasound fusion biopsy of the treatment site showed no cancer in 3 patients, microfocal Gleason 3 + 3 in another 3 and persistent intermediate risk prostate cancer in 4. Focal laser ablation of prostate cancer appears safe and feasible with the patient under local anesthesia in a urology clinic using magnetic resonance imaging-ultrasound fusion for guidance and thermal probes for monitoring. Further development is necessary to refine out of bore focal laser ablation and additional studies are needed to determine appropriate treatment margins and oncologic efficacy. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate cancer risk profiles of Asian-American men: disentangling the effects of immigration status and race/ethnicity.

PubMed

Lichtensztajn, Daphne Y; Gomez, Scarlett Lin; Sieh, Weiva; Chung, Benjamin I; Cheng, Iona; Brooks, James D

2014-04-01

Asian-American men with prostate cancer have been reported to present with higher grade and later stage disease than white American men. However, Asian-American men comprise a heterogeneous population with distinct health outcomes. We compared prostate cancer risk profiles among the diverse racial and ethnic groups in California. We used data from the California Cancer Registry on 90,845 nonHispanic white, nonHispanic black and Asian-American men diagnosed with prostate cancer between 2004 and 2010. Patients were categorized into low, intermediate and high risk groups based on clinical stage, Gleason score and prostate specific antigen at diagnosis. Using polytomous logistic regression we estimated adjusted ORs for the association of race/ethnicity and nativity with risk group. In addition to the nonHispanic black population, 6 Asian-American groups (United States born Chinese, foreign born Chinese, United States born Japanese, foreign born Japanese, foreign born Filipino and foreign born Vietnamese) were more likely to have an unfavorable risk profile compared to nonHispanic white men. The OR for high vs intermediate risk disease ranged from 1.23 (95% CI 1.02-1.49) for United States born Japanese men to 1.45 (95% CI 1.31-1.60) for foreign born Filipino men. These associations appeared to be driven by higher grade and prostate specific antigen rather than by advanced clinical stage at diagnosis. In this large, ethnically diverse, population based cohort Asian-American men were more likely to have an unfavorable risk profile at diagnosis. This association varied by racial/ethnic group and nativity, and was not attributable to later stage at diagnosis. This suggests that Asian men may have biological differences that predispose to more severe disease. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Evaluation of Adherence to Quality Measures for Prostate Cancer Radiotherapy in the United States: Results from the Quality Research in Radiation Oncology (QRRO) Survey

PubMed Central

Zelefsky, Michael J.; Lee, W. Robert; Zietman, Anthony; Khalid, Najma; Crozier, Cheryl; Owen, Jean; Wilson, J. Frank

2012-01-01

Purpose To test the feasibility of using proposed quality indicators to assess radiotherapy quality in prostate cancer management based on a 2007 stratified random survey of treating academic and non-academic US institutions. Methods and Materials 414 patients with clinically localized prostate cancer treated with external beam radiotherapy (EBRT) or brachytherapy were selected from 45 institutions. Indicators used as specific measurable clinical performance measures to represent surrogates for quality of radiotherapy delivery included established measures, such as the use of prescription doses ≥75 Gy for intermediate- and high-risk EBRT patients and androgen-deprivation therapy (ADT) in conjunction with EBRT for patients with high-risk disease, and emerging measures, including daily target localization (image-guidance) to correct for organ motion for EBRT patients. Results 167 patients (47%) were treated with 6 MV photons, 31 (9%) were treated with 10 MV, 65 (18%) received 15 MV, and the remaining 90 (26%) 16–23 MV. For intermediate- plus high-risk patients (n=181), 78% were treated to ≥75 Gy. Among favorable-risk patients, 72% were treated to ≥75 Gy. Among high-risk EBRT patients, 60 (87%) were treated with ADT in conjunction with EBRT and 13% (n=9) with radiotherapy alone. Among low- and intermediate-risk patients, 10% and 42%, respectively, were treated with ADT plus EBRT. For 24% of EBRT patients (85/354), weekly electronic portal imaging was obtained as verification films without daily target localization and the remaining 76% were treated with daily localization of the target using various methods. Conclusions Adherence to defined quality indicators was observed in a majority of patients. ≈90% of high-risk patients are treated with ADT plus EBRT and ≈80% of intermediate- and high-risk patients receive prescription doses >=75 Gy, consistent with the published results of randomized trials. PMID:23471563

Evaluation of Adherence to Quality Measures for Prostate Cancer Radiotherapy in the United States: Results from the Quality Research in Radiation Oncology (QRRO) Survey.

PubMed

Zelefsky, Michael J; Lee, W Robert; Zietman, Anthony; Khalid, Najma; Crozier, Cheryl; Owen, Jean; Wilson, J Frank

2013-01-01

To test the feasibility of using proposed quality indicators to assess radiotherapy quality in prostate cancer management based on a 2007 stratified random survey of treating academic and non-academic US institutions. 414 patients with clinically localized prostate cancer treated with external beam radiotherapy (EBRT) or brachytherapy were selected from 45 institutions. Indicators used as specific measurable clinical performance measures to represent surrogates for quality of radiotherapy delivery included established measures, such as the use of prescription doses ≥75 Gy for intermediate- and high-risk EBRT patients and androgen-deprivation therapy (ADT) in conjunction with EBRT for patients with high-risk disease, and emerging measures, including daily target localization (image-guidance) to correct for organ motion for EBRT patients. 167 patients (47%) were treated with 6 MV photons, 31 (9%) were treated with 10 MV, 65 (18%) received 15 MV, and the remaining 90 (26%) 16-23 MV. For intermediate- plus high-risk patients (n=181), 78% were treated to ≥75 Gy. Among favorable-risk patients, 72% were treated to ≥75 Gy. Among high-risk EBRT patients, 60 (87%) were treated with ADT in conjunction with EBRT and 13% (n=9) with radiotherapy alone. Among low- and intermediate-risk patients, 10% and 42%, respectively, were treated with ADT plus EBRT. For 24% of EBRT patients (85/354), weekly electronic portal imaging was obtained as verification films without daily target localization and the remaining 76% were treated with daily localization of the target using various methods. Adherence to defined quality indicators was observed in a majority of patients. ≈90% of high-risk patients are treated with ADT plus EBRT and ≈80% of intermediate- and high-risk patients receive prescription doses >=75 Gy, consistent with the published results of randomized trials.

Performance characteristics of prostate-specific antigen density and biopsy core details to predict oncological outcome in patients with intermediate to high-risk prostate cancer underwent robot-assisted radical prostatectomy.

PubMed

Yashi, Masahiro; Nukui, Akinori; Tokura, Yuumi; Takei, Kohei; Suzuki, Issei; Sakamoto, Kazumasa; Yuki, Hideo; Kambara, Tsunehito; Betsunoh, Hironori; Abe, Hideyuki; Fukabori, Yoshitatsu; Nakazato, Yoshimasa; Kaji, Yasushi; Kamai, Takao

2017-06-23

Many urologic surgeons refer to biopsy core details for decision making in cases of localized prostate cancer (PCa) to determine whether an extended resection and/or lymph node dissection should be performed. Furthermore, recent reports emphasize the predictive value of prostate-specific antigen density (PSAD) for further risk stratification, not only for low-risk PCa, but also for intermediate- and high-risk PCa. This study focused on these parameters and compared respective predictive impact on oncologic outcomes in Japanese PCa patients. Two-hundred and fifty patients with intermediate- and high-risk PCa according to the National Comprehensive Cancer Network (NCCN) classification, that underwent robot-assisted radical prostatectomy at a single institution, and with observation periods of longer than 6 months were enrolled. None of the patients received hormonal treatments including antiandrogens, luteinizing hormone-releasing hormone analogues, or 5-alpha reductase inhibitors preoperatively. PSAD and biopsy core details, including the percentage of positive cores and the maximum percentage of cancer extent in each positive core, were analyzed in association with unfavorable pathologic results of prostatectomy specimens, and further with biochemical recurrence. The cut-off values of potential predictive factors were set through receiver-operating characteristic curve analyses. In the entire cohort, a higher PSAD, the percentage of positive cores, and maximum percentage of cancer extent in each positive core were independently associated with advanced tumor stage ≥ pT3 and an increased index tumor volume > 0.718 ml. NCCN classification showed an association with a tumor stage ≥ pT3 and a Gleason score ≥8, and the attribution of biochemical recurrence was also sustained. In each NCCN risk group, these preoperative factors showed various associations with unfavorable pathological results. In the intermediate-risk group, the percentage of positive cores showed an independent predictive value for biochemical recurrence. In the high-risk group, PSAD showed an independent predictive value. PSAD and biopsy core details have different performance characteristics for the prediction of oncologic outcomes in each NCCN risk group. Despite the need for further confirmation of the results with a larger cohort and longer observation, these factors are important as preoperative predictors in addition to the NCCN classification for a urologic surgeon to choose a surgical strategy.

Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression.

PubMed

Richman, Erin L; Stampfer, Meir J; Paciorek, Alan; Broering, Jeanette M; Carroll, Peter R; Chan, June M

2010-03-01

Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004-2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.

Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression1234

PubMed Central

Richman, Erin L; Stampfer, Meir J; Paciorek, Alan; Broering, Jeanette M; Carroll, Peter R; Chan, June M

2010-01-01

Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004–2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk. PMID:20042525

Update on cryotherapy for localized prostate cancer.

PubMed

Ritch, Chad R; Katz, Aaron E

2009-05-01

Stage migration has led to an increased incidence of localized and low-risk prostate cancer. Intermediate-term data are emerging on the efficacy of cryotherapy, but direct comparison to other therapeutic modalities is difficult as the parameters for recurrence are not well defined. Studies using the American Society for Therapeutic Radiation and Oncology and the Phoenix (nadir plus 2) criteria for biochemical recurrence show that primary cryotherapy appears to be comparable for low-risk prostate cancer as other treatment modalities. In addition, health-related quality-of-life measures have improved with the most recent third-generation systems demonstrating low incontinence and urethrorectal fistula rates. Erectile dysfunction is high with whole gland ablation, but focal therapy may reduce these rates while still ablating unilateral cancerous tissue. Prostate cryotherapy for localized prostate cancer is an evolving but viable therapeutic option. Long-term data are still needed to establish a definitive role for cryosurgery in prostate cancer treatment.

Detectable end of radiation prostate specific antigen assists in identifying men with unfavorable intermediate-risk prostate cancer at high risk of distant recurrence and cancer-specific mortality.

PubMed

Hayman, Jonathan; Phillips, Ryan; Chen, Di; Perin, Jamie; Narang, Amol K; Trieu, Janson; Radwan, Noura; Greco, Stephen; Deville, Curtiland; McNutt, Todd; Song, Daniel Y; DeWeese, Theodore L; Tran, Phuoc T

2018-06-01

Undetectable End of Radiation PSA (EOR-PSA) has been shown to predict improved survival in prostate cancer (PCa). While validating the unfavorable intermediate-risk (UIR) and favorable intermediate-risk (FIR) stratifications among Johns Hopkins PCa patients treated with radiotherapy, we examined whether EOR-PSA could further risk stratify UIR men for survival. A total of 302 IR patients were identified in the Johns Hopkins PCa database (178 UIR, 124 FIR). Kaplan-Meier curves and multivariable analysis was performed via Cox regression for biochemical recurrence free survival (bRFS), distant metastasis free survival (DMFS), and overall survival (OS), while a competing risks model was used for PCa specific survival (PCSS). Among the 235 patients with known EOR-PSA values, we then stratified by EOR-PSA and performed the aforementioned analysis. The median follow-up time was 11.5 years (138 months). UIR was predictive of worse DMFS and PCSS (P = 0.008 and P = 0.023) on multivariable analysis (MVA). Increased radiation dose was significant for improved DMFS (P = 0.016) on MVA. EOR-PSA was excluded from the models because it did not trend towards significance as a continuous or binary variable due to interaction with UIR, and we were unable to converge a multivariable model with a variable to control for this interaction. However, when stratifying by detectable versus undetectable EOR-PSA, UIR had worse DMFS and PCSS among detectable EOR-PSA patients, but not undetectable patients. UIR was significant on MVA among detectable EOR-PSA patients for DMFS (P = 0.021) and PCSS (P = 0.033), while RT dose also predicted PCSS (P = 0.013). EOR-PSA can assist in predicting DMFS and PCSS among UIR patients, suggesting a clinically meaningful time point for considering intensification of treatment in clinical trials of intermediate-risk men. © 2018 Wiley Periodicals, Inc.

Prediction of Prostate Cancer Recurrence Using Quantitative Phase Imaging

NASA Astrophysics Data System (ADS)

Sridharan, Shamira; Macias, Virgilia; Tangella, Krishnarao; Kajdacsy-Balla, André; Popescu, Gabriel

2015-05-01

The risk of biochemical recurrence of prostate cancer among individuals who undergo radical prostatectomy for treatment is around 25%. Current clinical methods often fail at successfully predicting recurrence among patients at intermediate risk for recurrence. We used a label-free method, spatial light interference microscopy, to perform localized measurements of light scattering in prostatectomy tissue microarrays. We show, for the first time to our knowledge, that anisotropy of light scattering in the stroma immediately adjoining cancerous glands can be used to identify patients at higher risk for recurrence. The data show that lower value of anisotropy corresponds to a higher risk for recurrence, meaning that the stroma adjoining the glands of recurrent patients is more fractionated than in non-recurrent patients. Our method outperformed the widely accepted clinical tool CAPRA-S in the cases we interrogated irrespective of Gleason grade, prostate-specific antigen (PSA) levels and pathological tumor-node-metastasis (pTNM) stage. These results suggest that QPI shows promise in assisting pathologists to improve prediction of prostate cancer recurrence.

Diagnosis and treatment for clinically localized prostate cancer. Adherence to the European Association of Urology clinical guidelines in a nationwide population-based study - GESCAP group.

PubMed

Gómez-Veiga, F; Rodríguez-Antolín, A; Miñana, B; Hernández, C; Suárez, J F; Fernández-Gómez, J M; Unda, M; Burgos, J; Alcaraz, A; Rodríguez, P; Medina, R; Castiñeiras, J; Moreno, C; Pedrosa, E; Cózar, J M

To assess the adherence to European Association of Urology (EAU) guidelines in the management of prostate cancer (PCa) in Spain. Epidemiological, population-based, study including a national representative sample of 3,918 incident patients with histopathological confirmation during 2010; 95% of the patient's sample was followed up for at least one year. Diagnosis along with treatment related variables (for localized PCa -low, intermediate, high and locally-advanced by D'Amico risk stratification) was recorded. Differences between groups were tested with Chi-squared and Kruskal-Wallis tests. Mean (SD) age of PCa patients was 68.48 (8.18). Regarding diagnostic by biopsy procedures, 64.56% of all patients had 8-12 cores in first biopsy and 46.5% of the patients over 75 years, with PSA<10ng/mL were biopsied. Staging by Computer Tomography (CT) or Bone Scan (BS) was used for determining tumor extension in 60.09% of high-risk cases and was applied differentially depending on patients' age; 3,293 (84.05%) patients received a treatment for localized PCa. Radical prostatectomy was done in 1,277 patients and 206 out of these patients also had a lymphadenectomy, being 4.64% low-risk, 22.81% intermediate-risk and 36.00% high-risk patients; 86.08% of 1,082 patients who had radiotherapy were treated with 3D or IMRT and 35.77% received a dose ≥75Gy; 419 patients were treated with brachytherapy (BT): 54.81% were low-risk patients, 22.84% intermediate-risk and 12.98% high-risk. Hormonotherapy (HT, n=521) was applied as single therapy in 9.46% of low-risk and 17.92% of intermediate-risk patients. Additionally, HT was combined with RT in 14.34% of lower-risk patients and 58.26% of high-risk patients, and 67.19% low-intermediate risk with RT and/or BT received neoadjuvant/concomitant/adjuvant HT. Finally, 83.75% of high-risk patients undergoing RT and/or BT also received HT. Although EAU guidelines for PCa management are easily available in Europe, the adherence to their recommendations is low, finding the highest discrepancies in the need for a prostate biopsy and the diagnostic methods. Improve information and educational programs could allow a higher adherence to the guidelines and reduce the variability in daily practice. (Controlled-trials.com: ISRCTN19893319). Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Primary treatments for clinically localized prostate cancer: a comprehensive lifetime cost-utility analysis

PubMed Central

Cooperberg, Matthew R.; Ramakrishna, Naren R.; Duff, Steven B.; Hughes, Kathleen E.; Sadownik, Sara; Smith, Joseph A.; Tewari, Ashutosh K.

2012-01-01

Objectives To characterize the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (dose-escalated 3-dimensional conformal radiation, intensity-modulated radiation, brachytherapy, or combination), using a comprehensive, lifetime decision analytic model. Patients and Methods A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes following primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. Patients could experience remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the U.S. payer perspective, with incorporation of patient costs in a sensitivity analysis. Results Differences in quality-adjusted life years across modalities were modest, ranging from 10.3 to 11.3 for low-risk patients, 9.6 to 10.5 for intermediate-risk patients, and 7.8 to 9.3 for high-risk patients. There were no statistically significant differences among surgical modalities, which tended to be more effective than radiation modalities, with the exception of combination external beam + brachytherapy for high-risk disease. Radiation modalities were consistently more expensive than surgical modalities; costs ranged from $19,901 (robot-assisted prostatectomy for low-risk disease) to $50,276 (combination radiation for high-risk disease). These findings were robust to an extensive set of sensitivity analyses. Conclusions Our analysis found small differences in outcomes and substantial differences in payer and patient costs across treatment alternatives. These findings may inform future policy discussions regarding strategies to improve efficiency of treatment selection for localized prostate cancer. PMID:23279038

High-Intensity Focused Ultrasound (HIFU) Using Sonablate® Devices for the Treatment of Benign Prostatic Hyperplasia and Localized Prostate Cancer: 18-year experience

NASA Astrophysics Data System (ADS)

Uchida, Toyoaki

2011-09-01

From 1993 to 2010, we have treated 156 patients benign prostatic hyperplasia (BPH) and 1,052 patients localized prostate cancer high-intensity focused ultrasound (HIFU). Four different HIFU devices, SonablateR-200, SonablateR-500, SonablateR-500 version 4 and Sonablate® TCM, have been used for this study. Clinical outcome of HIFU for BPH did not show any superior effects to transurethral resection of the prostate, laser surgery or transurethral vapolization of the prostate. However, HIFU appears to be a safe and minimally invasive therapy for patients with localized prostate cancer, especially low- and intermediate-risk patients. The rate of clinical outcome has significantly improved over the years due to technical improvements in the device.

Tumor Volume and Metabolism of Prostate Cancer Determined by Proton Magnetic Resonance Spectroscopic Imaging at 3T Without Endorectal Coil Reveal Potential Clinical Implications in the Context of Radiation Oncology;Prostate cancer; Magnetic resonance spectroscopic imaging; Radiation oncology; Tumor volume; Biomarkers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crehange, Gilles, E-mail: gcrehange@cgfl.fr; Parfait, Sebastien; Liegard, Melanie

2011-07-15

Purpose: To determine whether a relationship exists between the tumor volume (TV) or relative choline content determined using magnetic resonance spectroscopy imaging (MRSI) at 3T and the clinical prognostic parameters for patients with localized prostate cancer (PCa). Methods and Materials: A total of 72 men (mean age, 67.8 {+-} 6.2 years) were stratified as having low-risk (n = 26), intermediate-risk (n = 24), or high-risk (n = 22) PCa. MRSI was performed at 3T using a phased-array coil. Spectra are expressed as the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamines plus creatine/citrate ratios. The mean ratiomore » of the most pathologic voxels and the MRSI-based TV were also determined. Results: The mean values of the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamine plus creatine/citrate ratios were greater for Stage T2b or greater tumors vs. Stage T2a or less tumors: 7.53 {+-} 13.60 vs. 2.31 {+-} 5.65 (p = .018), 8.98 {+-} 14.58 vs. 2.56 {+-} 5.70 (p = .016), and 10.32 {+-} 15.47 vs. 3.55 {+-} 6.16 (p = .014), respectively. The mean MRSI-based TV for Stage T2b or greater and Stage T2a or less tumors was significantly different (2.23 {+-} 2.62 cm{sup 3} vs. 1.26 {+-} 2.06 cm{sup 3}, respectively; p = .030). This TV correlated with increased prostate-specific antigen levels (odds ratio, 1.293; p = .012). Patients with high-risk PCa had a larger TV than did the patients with intermediate-risk PCa. A similar result was found for the intermediate-risk group compared with the low-risk group (odds ratio, 1.225; p = .041). Conclusion: Biomarkers expressing the relative choline content and TV were significant parameters for the localization of PCa and could be helpful for determining the prognosis more accurately.« less

Identifying Differences Between Biochemical Failure and Cure: Incidence Rates and Predictors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vicini, Frank A., E-mail: fvicini@beaumont.edu; Shah, Chirag; Kestin, Larry

2011-11-15

Background: Patients treated with radiation therapy (RT) for prostate cancer were evaluated to estimate the length of time required to document biochemical cure (BC) after treatment and the variables associated with long-term treatment efficacy. Patients and Methods: 2,100 patients received RT alone for localized prostate carcinoma (external-beam RT, n = 1,504; brachytherapy alone, n = 241; or brachytherapy + pelvic radiation, n = 355). The median external-beam dose was 68.4 Gy, and the median follow-up time was 8.6 years. Biochemical failure (BF) was defined according to the Phoenix definition. Results: Biochemical failure was experienced by 685 patients (32.6%). The medianmore » times to BF for low-, intermediate-, and high-risk groups were 6.0, 5.6, and 4.5 years respectively (p < 0.001). The average annual incidence rates of BF for years 1-5, 5-10,11-15, and 16-20 in low-risk patients were 2.0%, 2.0%, 0.3%, and 0.06% (p < 0.001); for intermediate-risk patients, 4%, 3%, 0.3%, and 0% (p < 0.001); and for high-risk patients, 10.0%, 5.0%, 0.3%, and 0.3% (p < 0.001). After 5 years of treatment, 36.9% of all patients experienced BF. The percentage of total failures occurring during years 1-5, 5-10, 11-15, and 16-20 were 48.7%, 43.5%, 6.5%, and 1.3% for low-risk patients; 64.0%, 32.2%, 3.8%, and 0% for intermediate-risk patients; and 71.9%, 25.9%, 1.1%, and 1.1% for high-risk patients, respectively. Increasing time to nadir was associated with increased time to BF. On multivariate analysis, factors significantly associated with 10-year BC included prostate-specific antigen nadir and time to nadir. Conclusions: The incidence rates for BF did not plateau until later than 10 years after treatment, suggesting that extended follow-up time is required to monitor patients after treatment. Prostate-specific antigen nadir and time to nadir have the strongest association with long-term BC.« less

[High-intensity focused ultrasound (HIFU): our experience in the treatment of prostate cancer relapsing after radiotherapy].

PubMed

Giovanessi, Luca; Peroni, Angelo; Mirabella, Giuseppe; Fugini, Andrea Vismara; Zani, Danilo; Cunico, Sergio Cosciani; Simeone, Claudio

2011-01-01

The aim of the study is to evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) treatment in patients with local prostate cancer recurrence after radiotherapy. From February 2009 to June 2010, 14 patients with prostate cancer recurrence after radiotherapy were selected for HIFU treatment; all patients had a positive TRUS-guided biopsy and the absence of distant metastases was confirmed by computer tomography, PET choline or bone scintigraphy. We classified all patients in 3 groups using D'Amico's classification: 4 patients high risk (PSA >20 ng/ml - 8≤ Gleason Score≤ 10 - clinical stage≥T2c), 8 patients intermediate risk (10 PSAnadir+1.2ng/ml) or after adjuvant therapy introduction. All complications were recorded. Of the 14 patients selected, 12 patients underwent HIFU treatments; 2 patients were excluded because of rectal strictures induced by radiotherapy. At a mean 13 months' follow-up, biochemical success rate was obtained in 1 of the high risk patients and in 5 of the low and intermediate risk patients; 1 man died for a disease not correlated with prostate cancer recurrence. Complications included urinary tract infection, acute urinary retentions, urethral strictures and light stress incontinence. In our experience salvage HIFU is a safe treatment option for local relapse after radiotherapy; its efficacy depends on a careful patient selection.

A Prospective Trial of Intensity Modulated Radiation Therapy (IMRT) Incorporating a Simultaneous Integrated Boost for Prostate Cancer: Long-term Outcomes Compared With Standard Image Guided IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schild, Michael H.; Schild, Steven E., E-mail: sschild@mayo.edu; Wong, William W.

Purpose: This report describes the long-term outcomes of a prospective trial of intensity modulated radiation therapy (IMRT), integrating a {sup 111}In capromab pendetide (ProstaScint) scan-directed simultaneous integrated boost (SIB) for localized prostate cancer. Methods and Materials: Seventy-one patients with T1N0M0 to T4N0M0 prostate cancer were enrolled, and their ProstaScint and pelvic computed tomography scans were coregistered for treatment planning. The entire prostate received 75.6 Gy in 42 fractions with IMRT, whereas regions of increased uptake on ProstaScint scans received 82 Gy as an SIB. Patients with intermediate- and high-risk disease also received 6 months and 12 months of adjuvant hormonal therapy, respectively. Results: The studymore » enrolled 31 low-, 30 intermediate-, and 10 high-risk patients. The median follow-up was 120 months (range, 24-150 months). The 10-year biochemical control rates were 85% for the entire cohort and 84%, 84%, and 90% for patients with low-, intermediate-, and high-risk disease, respectively. The 10-year survival rate of the entire cohort was 69%. Pretreatment prostate-specific antigen level >10 ng/mL and boost volume of >10% of the prostate volume were significantly associated with poorer biochemical control and survival. The outcomes were compared with those of a cohort of 302 patients treated similarly but without the SIB and followed up for a median of 91 months (range, 6-138 months). The 5- and 10-year biochemical control rates were 86% and 61%, respectively, in patients without the SIB compared with 94% and 85%, respectively, in patients in this trial who received the SIB (P=.02). The cohort that received an SIB did not have increased toxicity. Conclusions: The described IMRT strategy, integrating multiple imaging modalities to administer 75.6 Gy to the entire prostate with a boost dose of 82 Gy, was feasible. The addition of the SIB was associated with greater biochemical control but not toxicity. Modern imaging technology can be used to locally intensify the dose to tumors and spare normal tissues, producing very favorable long-term biochemical disease control.« less

Twelve years' experience with high-intensity focused ultrasound (HIFU) using sonablate™ devices for the treatment of localized prostate cancer

NASA Astrophysics Data System (ADS)

Uchida, Toyoaki; Nakano, Muyura; Shoji, Sunao; Nagata, Yoshihiro; Usui, Yukio; Terachi, Toshiro

2012-10-01

To report on the long-term results of high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. Patients with clinical Stage T1c-T3N0M0, biopsy proven, localized prostate cancer, with a serum prostate specific antigen (PSA) level of <30 ng/ml, any Gleason score were included. All patients underwent HIFU using the Sonablate™ (S) device and were required to have a minimal follow-up of 2 years after the last HIFU session to be included in this analysis. Four different generation HIFU devices, S200, S500, S500 version 4 and S500 TCM, have been used for this study. Biochemical failure was defined according to the Phoenix definition (PSA nadir+2ng/ml). Seven hundred and fifty-three men with prostate cancer were included. The patients were divided into two groups: in the Former group, 421 patients were treated with S200 and 500 from 1990 to 2005; in the Latter group, 332 patients were treated with S500 ver. 4 and TCM from 2005 to 2009. The mean age, PSA, Gleason score, operation time, and follow-up period in the Former and Latter groups were 68 and 67 years, 11.3 and 9.7 ng/ml, 6.2 and 6.6, 167 and 101 min, and 49 and 38 months, respectively. The biochemical disease-free rate (BDFR) in the groups at 5 years was, respectively, 67% and 53%, and was 50% at 10 years in the Former group (p<0.0001). The BDFR in patients in the low-, intermediate-, and high-risk groups in the Former group at 5 and 10 years were 68% and 65%, 52% and 48%, and 43% and 40%, respectively (p<0.0001). The BDFR in patients in the low-, intermediate-, and high-risk groups in the Latter group at 5 years were 83%, 76%, and 42% (p<0.0001). The negative prostate biopsy rate in the Former and Latter groups was 81% and 93%, respectively. Postoperative erectile dysfunction was noted in 45%, 38%, and 24% of patients at 6 months, 12 months, and 2 years after HIFU. The results after long-term follow-up have indicated that HIFU is an efficient and safe treatment for patients with localized prostate cancer, especially low-and intermediate-risk patients.

A single institution analysis of low-dose-rate brachytherapy: 5-year reported survival and late toxicity outcomes

PubMed Central

Spencer, Sandra; Guerrieri, Mario; Ding, Wei; Goharian, Mehran; Ho, Huong; Ng, Michael; Healey, Danielle; Tan, Alwin; Cham, Chee; Joon, Daryl Lim; Lawrentschuk, Nathan; Travis, Douglas; Sengupta, Shomik; Chan, Yee; Troy, Andrew; Pham, Trung; Clarke, David; Liodakis, Peter; Bolton, Damien

2018-01-01

Purpose To report the 5-year biochemical relapse-free survival (BRFS), overall survival (OS), and long-term toxicity outcomes of patients treated with low-dose-rate (LDR) brachytherapy as monotherapy for low- to intermediate-risk prostate cancer. Material and methods Between 2004 and 2011, 371 patients were treated with LDR brachytherapy as monotherapy. Of these, 102 patients (27%) underwent transurethral resection of the prostate (TURP) prior to implantation. Follow-up was performed every 3 months for 12 months, then every 6 months over 4 years and included prostate specific antigen evaluation. The biochemical relapse-free survival (BRFS) was defined according to the Phoenix criteria. Acute and late toxicities were documented using the Common Terminology Criteria for Adverse Events version 4.0. The BRFS and OS estimates were calculated using Kaplan-Meier plots. Univariate and multivariate analyses were performed to evaluate outcomes by pre-treatment clinical prognostic factors and radiation dosimetry. Results The median follow-up of all patients was 5.45 years. The 5-year BRFS and OS rates were 95% and 96%, respectively. The BRFS rates for patients with Gleason score (GS) > 7 and GS ≤ 6 were 96% and 91% respectively (p = 0.06). On univariate analysis, T1 and T2 staging, risk-group classification, and prostate volumes had no impact on survival at 5 years (p > 0.1). Late grade 2 and 3 genitourinary (GU) toxicities were observed in 10% and 5% of patients respectively. Additionally, patients with prior TURP had a greater incidence of late grade 2 or 3 urinary retention (p = 0.001). There were 14 deaths in total; however, none were attributed to prostate cancer. Conclusions LDR brachytherapy is an effective treatment option in low- to intermediate-risk prostate cancer patients. We observed low biochemical relapse rates and minimal GU toxicities several years after treatment in patients with or without TURP. However, a small risk of urinary retention was observed in some patients. PMID:29789764

Radical prostatectomy--long-term oncological outcome from a community hospital.

PubMed

Tol-Fakkar, Maria; Hermansson, Carl Gustaf; Hugosson, Jonas; Pedersen, Knud; Aus, Gunnar

2003-01-01

Radical prostatectomy has recently been shown to prolong cancer-specific survival compared to watchful waiting in patients with localized prostate cancer. Most patients who seek medical advice for this disease are treated in hospitals in which the operation is performed relatively infrequently. The aim of this study is to report the oncological outcome at intermediate- to long-term follow-up after radical prostatectomy performed in a community hospital. A total of 148 patients underwent radical prostatectomy at Ryhov County Hospital between 1985 and 1997. Patients without T3 tumours, prostate-specific antigen (PSA) >10 ng/ml or poorly differentiated tumours were judged to be in a low-risk group, those with one risk factor to be in an intermediate group and those with two or more factors to be in a high-risk group. The projected biochemical disease free- and cancer-specific survival rates were compared between these risk groups. Median follow-up was 96 months for surviving patients. Patients in the low- and intermediate risk groups had equal 10-year PSA-free survival rates of 68.8%, while that in the high-risk group was only 19.3% (9-year data). Corresponding cancer-specific survival rates were 93% and 84%, respectively. The oncological outcome seems comparable to that reported in the literature, even when the operation is performed in a low-volume community-based setting.

A Specific Mapping Study Using Fluorescence Sentinel Lymph Node Detection in Patients with Intermediate- and High-risk Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection.

PubMed

Nguyen, Daniel P; Huber, Philipp M; Metzger, Tobias A; Genitsch, Vera; Schudel, Hans H; Thalmann, George N

2016-11-01

Sentinel lymph node (SLN) detection techniques have the potential to change the standard of surgical care for patients with prostate cancer. We performed a lymphatic mapping study and determined the value of fluorescence SLN detection with indocyanine green (ICG) for the detection of lymph node metastases in intermediate- and high-risk patients undergoing radical prostatectomy and extended pelvic lymph node dissection. A total of 42 patients received systematic or specific ICG injections into the prostate base, the midportion, the apex, the left lobe, or the right lobe. We found (1) that external and internal iliac regions encompass the majority of SLNs, (2) that common iliac regions contain up to 22% of all SLNs, (3) that a prostatic lobe can drain into the contralateral group of pelvic lymph nodes, and (4) that the fossa of Marcille also receives significant drainage. Among the 12 patients who received systematic ICG injections, 5 (42%) had a total of 29 lymph node metastases. Of these, 16 nodes were ICG positive, yielding 55% sensitivity. The complex drainage pattern of the prostate and the low sensitivity of ICG for the detection of lymph node metastases reported in our study highlight the difficulties related to the implementation of SNL techniques in prostate cancer. There is controversy about how extensive lymph node dissection (LND) should be during prostatectomy. We investigated the lymphatic drainage of the prostate and whether sentinel node fluorescence techniques would be useful to detect node metastases. We found that the drainage pattern is complex and that the sentinel node technique is not able to replace extended pelvic LND. Copyright © 2016. Published by Elsevier B.V.

Influence of Comorbidity on the Risk of Mortality in Men With Unfavorable-Risk Prostate Cancer Undergoing High-Dose Radiation Therapy Alone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huynh, Mai Anh, E-mail: mahuynh@lroc.harvard.edu; Chen, Ming-Hui; Wu, Jing

Purpose: To explore whether a subgroup of men with unfavorable-risk prostate cancer (PC) exists in whom high-dose radiation therapy (RT) alone is sufficient to avoid excess PC death due to competing risk from cardiometabolic comorbidity. Methods and Materials: This was a cohort study of 7399 men in whom comorbidity (including congestive heart failure, diabetes mellitus, or myocardial infarction) was assessed and recorded with T1-3NxM0 PC treated with brachytherapy with or without neoadjuvant RT, October 1997 to May 2013 at a single providing institution. Cox and competing risks regression analyses were used to assess whether men with unfavorable–intermediate/high-risk versus favorable–intermediate/low-risk PC weremore » at increased risk of PC-specific, all-cause, or other-cause mortality (PCSM, ACM, OCM), adjusting for number of comorbidities, age at and year of brachytherapy, RT use, and an RT treatment propensity score. Results: After a median follow-up of 7.7 years, 935 men died: 80 of PC and 855 of other causes. Among men with no comorbidity, PCSM risk (adjusted hazard ratio [AHR] 2.74 [95% confidence interval (CI) 1.49-5.06], P=.001) and ACM risk (AHR 1.30 [95% CI 1.07-1.58], P=.007) were significantly increased in men with unfavorable–intermediate/high-risk PC versus favorable–intermediate/low-risk PC, with no difference in OCM (P=.07). Although PCSM risk was increased in men with 1 comorbidity (AHR 2.87 [95% CI 1.11-7.40], P=.029), ACM risk was not (AHR 1.03 [95% CI 0.78-1.36], P=.84). Neither PCSM risk (AHR 4.39 [95% CI 0.37-51.98], P=.24) or ACM risk (AHR 1.43 [95% CI 0.83-2.45], P=.20) was increased in men with 2 comorbidities. Conclusions: To minimize death from PC, high-dose RT alone may be sufficient treatment in men with 2 or more cardiometabolic comorbidities and unfavorable–intermediate- and high-risk PC.« less

Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer

PubMed Central

2011-01-01

Background The CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism. Methods Twenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires. Results All 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (p < 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism at one year post-treatment. Average EPIC sexual and hormonal scores were not significantly changed by one year post-treatment. Conclusions Hypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment. PMID:21439088

Association between surgeon and hospital characteristics and lymph node counts from radical prostatectomy and pelvic lymph node dissection.

PubMed

Wang, Elyn H; Yu, James B; Gross, Cary P; Abouassaly, Robert; Cherullo, Edward E; Smaldone, Marc C; Shah, Nilay D; Kiechle, Jonathon; Trinh, Quoc-Dien; Sun, Maxine; Kim, Simon P

2015-04-01

To assess whether surgical approach and hospital characteristics independently determine the number of lymph nodes (LNs) removed from prostate cancer patients undergoing radical prostatectomy (RP) and pelvic LN dissection (PLND). Using the National Cancer Database, we identified all surgically treated patients diagnosed with pretreatment intermediate- or high-risk prostate cancer from 2010 to 2011. The primary outcome was the number of LNs retrieved at the time of RP. Generalized estimating equations were used to assess for differences in the adjusted number of LNs retrieved after accounting for patient and hospital characteristics and surgical approach. Overall, 35,876 patients were diagnosed with intermediate-risk (61.2%) and high-risk (38.8%) prostate cancer and underwent RP and PLND.On multivariate analysis, open RP and high-volume and academic hospitals were independently associated with greater LN counts compared with robotic-assisted RP and medium or low and community hospitals, respectively (all P <.001). After adjusting for patient and hospital variables, higher adjusted LN counts were observed for open RP compared with robotic-assisted RP (7.1 vs 6.1; P <.001). Adjusted counts were also higher for high-volume hospitals compared with medium- or low-volume hospitals (7.8 vs 5.9; P <.001), and academic compared with community hospitals (7.3 vs 5.6; P <.001). Among patients with aggressive prostate cancer treated with RP and PLND, retrieval of LN counts varied by surgical approach and hospital characteristics. Copyright © 2015 Elsevier Inc. All rights reserved.

Emerging Roles of Human Prostatic Acid Phosphatase

PubMed Central

Kong, Hoon Young; Byun, Jonghoe

2013-01-01

Prostate cancer is one of the most prevalent non-skin related cancers. It is the second leading cause of cancer deaths among males in most Western countries. If prostate cancer is diagnosed in its early stages, there is a higher probability that it will be completely cured. Prostatic acid phosphatase (PAP) is a non-specific phosphomonoesterase synthesized in prostate epithelial cells and its level proportionally increases with prostate cancer progression. PAP was the biochemical diagnostic mainstay for prostate cancer until the introduction of prostate-specific antigen (PSA) which improved the detection of early-stage prostate cancer and largely displaced PAP. Recently, however, there is a renewed interest in PAP because of its usefulness in prognosticating intermediate to high-risk prostate cancers and its success in the immunotherapy of prostate cancer. Although PAP is believed to be a key regulator of prostate cell growth, its exact role in normal prostate as well as detailed molecular mechanism of PAP regulation is still unclear. Here, many different aspects of PAP in prostate cancer are revisited and its emerging roles in other environment are discussed. PMID:24009853

Receipt of Guideline-Concordant Treatment in Elderly Prostate Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Ronald C., E-mail: Ronald_chen@med.unc.edu; Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

2014-02-01

Purpose: To examine the proportion of elderly prostate cancer patients receiving guideline-concordant treatment, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: A total of 29,001 men diagnosed in 2004-2007 with localized prostate cancer, aged 66 to 79 years, were included. We characterized the proportion of men who received treatment concordant with the National Comprehensive Cancer Network guidelines, stratified by risk group and age. Logistic regression was used to examine covariates associated with receipt of guideline-concordant management. Results: Guideline concordance was 79%-89% for patients with low- or intermediate-risk disease. Among high-risk patients, 66.6% of those agedmore » 66-69 years received guideline-concordant management, compared with 51.9% of those aged 75-79 years. Discordance was mainly due to conservative management—no treatment or hormone therapy alone. Among the subgroup of patients aged ≤76 years with no measured comorbidity, findings were similar. On multivariable analysis, older age (75-79 vs 66-69 years, odds ratio 0.51, 95% confidence interval 0.50-0.57) was associated with a lower likelihood of guideline concordance for high-risk prostate cancer, but comorbidity was not. Conclusions: There is undertreatment of elderly but healthy patients with high-risk prostate cancer, the most aggressive form of this disease.« less

The Impact of Magnetic Resonance Imaging on Prediction of Extraprostatic Extension and Prostatectomy Outcome in Patients with Low-, Intermediate- and High-Risk Prostate Cancer: Try to Find a Standard.

PubMed

Radtke, Jan Philipp; Hadaschik, Boris A; Wolf, Maya B; Freitag, Martin T; Schwab, Constantin; Alt, Celine; Roth, Wilfried; Duensing, Stefan; Pahernik, Sascha A; Roethke, Matthias C; Schlemmer, Heinz-Peter; Hohenfellner, Markus; Teber, Dogu

2015-12-01

To investigate the value of multiparametric magnetic resonance imaging (mpMRI) and to predict extracapsular extension (ECE), seminal vesicle (SV) infiltration, and a negative surgical margin (SM) status at radical prostatectomy (RP) for different prostate cancer (PC) risk groups. In the study, 805 men underwent 3 tesla mpMRI without endorectal coil before MRI/transrectal ultrasonography-fusion guided prostate biopsy. MRIs were analyzed using the prostate imaging reporting and data system. The cohort was classified into risk groups according to National Comprehensive Cancer Network (NCCN) criteria. Of 132 men who subsequently underwent RP, pathologic stage and SM status at RP were used as reference. Retrospectively, we investigated a European Society of Urogenital Radiology (ESUR) score for ECE and SV-infiltration. Statistical analyses included regression analyses, receiver operating characteristics (ROC), and Youden Index to assess an ESUR-score cutoff. Area under the curve in ROC curve analyses was 0.82 for ESUR-ECE score to detect pT(3a)-disease and 0.77 for ESUR-SV score for pT(3b). Using a cutoff of 4 for ECE and of 2 for SV, the positive predictive value of the ECE-score for harboring pT(3) was 50.0%, 90.0%, and 88.8% for the low-, intermediate- and high-risk cohort. Retrospectively, the use of the ESUR-ECE score preoperatively would have changed the initial surgical plan, according to NCCN criteria, in 31.1% of patients. In the high-risk subgroup, 9/35 (25.7%) patients were correctly assessed as not harboring pT(3) by imaging (ECE score <4), and would have allowed secure robot-assisted radical prostatectomy and nerve-sparing surgery (NSS). When T3 suspicion on preoperative MRI would be taken into account, intraoperative frozen-sections (IFS) might avoid positive SM in 12/18 high-risk patients and an oncologic secure NSS in 8/20 intermediate-risk patients. Prediction of pT(3) disease is crucial to plan NSS and to achieve negative SM in RP. Standardized ECE scoring on mpMRI is an independent predictor of pT(3) and may help to plan RP with oncologic security, even in high-risk patients. In addition, it allows more accurate selection of a subgroup of patients for systematic and MRI-guided IFS.

Brachytherapy for Prostate Cancer: A Systematic Review

PubMed Central

Koukourakis, Georgios; Kelekis, Nikolaos; Armonis, Vassilios; Kouloulias, Vassilios

2009-01-01

Low-dose rate brachytherapy has become a mainstream treatment option for men diagnosed with prostate cancer because of excellent long-term treatment outcomes in low-, intermediate-, and high-risk patients. To a great extend due to patient lead advocacy for minimally invasive treatment options, high-quality prostate implants have become widely available in the US, Europe, and Japan. High-dose-rate (HDR) afterloading brachytherapy in the management of localised prostate cancer has practical, physical, and biological advantages over low-dose-rate seed brachytherapy. There are no free live sources used, no risk of source loss, and since the implant is a temporary procedure following discharge no issues with regard to radioprotection use of existing facilities exist. Patients with localized prostate cancer may benefit from high-dose-rate brachytherapy, which may be used alone in certain circumstances or in combination with external-beam radiotherapy in other settings. The purpose of this paper is to present the essentials of brachytherapies techniques along with the most important studies that support their effectiveness in the treatment of prostate cancer. PMID:19730753

Active Surveillance for Prostate Cancer: Contemporary State of Practice

PubMed Central

Tosoian, Jeffrey J.; Carter, H. Ballentine; Lepor, Abbey; Loeb, Stacy

2016-01-01

Prostate cancer remains among the most commonly diagnosed malignancies worldwide. Early diagnosis and curative treatment appear to improve survival in men with unfavorable-risk cancers, but significant concerns exist regarding the overdiagnosis and overtreatment of men with lower-risk cancers. To this end, active surveillance (AS) has emerged as a primary management strategy in men with favorable-risk disease, and contemporary data suggest that use of AS has increased worldwide. Although published surveillance cohorts differ by protocol, reported rates of metastatic disease and prostate cancer-specific mortality are exceedingly low in the intermediate term (5–10 years). Such outcomes appear to be closely associated with program-specific criteria for selection, monitoring, and intervention, suggesting that AS – like other management strategies – could be individualized based on the level of risk acceptable to patients in light of personal preferences. Additional data are needed to better establish the risks associated with AS and to identify patient-specific characteristics that could modify prognosis. PMID:26954332

A Biopsy-based 17-gene Genomic Prostate Score as a Predictor of Metastases and Prostate Cancer Death in Surgically Treated Men with Clinically Localized Disease.

PubMed

Van Den Eeden, Stephen K; Lu, Ruixiao; Zhang, Nan; Quesenberry, Charles P; Shan, Jun; Han, Jeong S; Tsiatis, Athanasios C; Leimpeter, Amethyst D; Lawrence, H Jeffrey; Febbo, Phillip G; Presti, Joseph C

2018-01-01

A 17-gene biopsy-based reverse transcription polymerase chain reaction assay, which provides a Genomic Prostate Score (GPS-scale 0-100), has been validated as an independent predictor of adverse pathology and biochemical recurrence after radical prostatectomy (RP) in men with low- and intermediate-risk prostate cancer (PCa). To evaluate GPS as a predictor of PCa metastasis and PCa-specific death (PCD) in a large cohort of men with localized PCa and long-term follow-up. A retrospective study using a stratified cohort sampling design was performed in a cohort of men treated with RP within Kaiser Permanente Northern California. RNA from archival diagnostic biopsies was assayed to generate GPS results. We assessed the association between GPS and time to metastasis and PCD in prespecified uni- and multivariable statistical analyses, based on Cox proportional hazard models accounting for sampling weights. The final study population consisted of 279 men with low-, intermediate-, and high-risk PCa between 1995 and 2010 (median follow-up 9.8 yr), and included 64 PCD and 79 metastases. Valid GPS results were obtained for 259 (93%). In univariable analysis, GPS was strongly associated with time to PCD, hazard ratio (HR)/20 GPS units=3.23 (95% confidence interval [CI] 1.84-5.65; p<0.001), and time to metastasis, HR/20 units=2.75 (95% CI 1.63-4.63; p<0.001). The association between GPS and both end points remained significant after adjusting for National Comprehensive Cancer Network, American Urological Association, and Cancer of the Prostate Risk Assessment (CAPRA) risks (p<0.001). No patient with low- or intermediate-risk disease and a GPS of<20 developed metastases or PCD (n=31). In receiver operating characteristic analysis of PCD at 10 yr, GPS improved the c-statistic from 0.78 (CAPRA alone) to 0.84 (GPS+CAPRA; p<0.001). A limitation of the study was that patients were treated during an era when definitive treatment was standard of care with little adoption of active surveillance. GPS is a strong independent predictor of long-term outcomes in clinically localized PCa in men treated with RP and may improve risk stratification for men with newly diagnosed disease. Many prostate cancers are slow growing and unlikely to spread or threaten a man's life, while others are more aggressive and require treatment. Increasingly, doctors are using new molecular tests, such as the17-gene Genomic Prostate Score (GPS), which can be performed at the time of initial diagnosis to help determine how aggressive a given patient's cancer may be. In this study, performed in a large community-based healthcare network, GPS was shown to be a strong predictor as to whether a man's prostate cancer will spread and threaten his life after surgery, providing information that may help patients and their doctors decide on the best course of management of their disease. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Higher-Than-Conventional Radiation Doses in Localized Prostate Cancer Treatment: A Meta-analysis of Randomized, Controlled Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Viani, Gustavo Arruda; Stefano, Eduardo Jose; Afonso, Sergio Luis

2009-08-01

Purpose: To determine in a meta-analysis whether the outcomes in men with localized prostate cancer treated with high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT), by quantifying the effect of the total dose of radiotherapy on biochemical control (BC). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing HDRT with CDRT for localized prostate cancer. To evaluate the dose-response relationship, we conducted a meta-regression analysis of BC ratios by means of weighted linear regression. Results:more » Seven RCTs with a total patient population of 2812 were identified that met the study criteria. Pooled results from these RCTs showed a significant reduction in the incidence of biochemical failure in those patients with prostate cancer treated with HDRT (p < 0.0001). However, there was no difference in the mortality rate (p = 0.38) and specific prostate cancer mortality rates (p = 0.45) between the groups receiving HDRT and CDRT. However, there were more cases of late Grade >2 gastrointestinal toxicity after HDRT than after CDRT. In the subgroup analysis, patients classified as being at low (p = 0.007), intermediate (p < 0.0001), and high risk (p < 0.0001) of biochemical failure all showed a benefit from HDRT. The meta-regression analysis also detected a linear correlation between the total dose of radiotherapy and biochemical failure (BC = -67.3 + [1.8 x radiotherapy total dose in Gy]; p = 0.04). Conclusions: Our meta-analysis showed that HDRT is superior to CDRT in preventing biochemical failure in low-, intermediate-, and high-risk prostate cancer patients, suggesting that this should be offered as a treatment for all patients, regardless of their risk status.« less

Hypofractionated Radiation Therapy (66 Gy in 22 Fractions at 3 Gy per Fraction) for Favorable-Risk Prostate Cancer: Long-term Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Nita; Faria, Sergio, E-mail: sergio.faria@muhc.mcgill.ca; Cury, Fabio

2013-07-01

Purpose: To report long-term outcomes of low- and intermediate-risk prostate cancer patients treated with high-dose hypofractionated radiation therapy (HypoRT). Methods and Materials: Patients with low- and intermediate-risk prostate cancer were treated using 3-dimensional conformal radiation therapy to a dose of 66 Gy in 22 daily fractions of 3 Gy without hormonal therapy. A uniform 7-mm margin was created around the prostate for the planning target volume, and treatment was prescribed to the isocenter. Treatment was delivered using daily ultrasound image-guided radiation therapy. Common Terminology Criteria for Adverse Events, version 3.0, was used to prospectively score toxicity. Biochemical failure was definedmore » as the nadir prostate-specific antigen level plus 2 ng/mL. Results: A total of 129 patients were treated between November 2002 and December 2005. With a median follow-up of 90 months, the 5- and 8-year actuarial biochemical control rates were 97% and 92%, respectively. The 5- and 8-year actuarial overall survival rates were 92% and 88%, respectively. Only 1 patient died from prostate cancer at 92 months after treatment, giving an 8-year actuarial cancer-specific survival of 98%. Radiation therapy was well tolerated, with 57% of patients not experiencing any acute gastrointestinal (GI) or genitourinary (GU) toxicity. For late toxicity, the worst grade ≥2 rate for GI and GU toxicity was 27% and 33%, respectively. There was no grade >3 toxicity. At last follow-up, the rate of grade ≥2 for both GI and GU toxicity was only 1.5%. Conclusions: Hypofractionation with 66 Gy in 22 fractions prescribed to the isocenter using 3-dimensional conformal radiation therapy produces excellent biochemical control rates, with moderate toxicity. However, this regimen cannot be extrapolated to the intensity modulated radiation therapy technique.« less

Salvage High-intensity Focused Ultrasound for the Recurrent Prostate Cancer after Radiotherapy

NASA Astrophysics Data System (ADS)

Shoji, S.; Nakano, M.; Omata, T.; Harano, Y.; Nagata, Y.; Usui, Y.; Terachi, T.; Uchida, T.

2010-03-01

To investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 20 cases treated using the Sonablate® 500 HIFU device, between August 28, 2002 and September 1, 2009, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. All men with presumed, organ-confined, recurrent disease following EBRT in 8 patients, brachytherapy in 7 patients or proton therapy in 5 patients treated with salvage HIFU were included. The patients were followed for a mean (range) of 16.0 (3-80) months. Biochemical disease-free survival (bDFS) rates in patients with low-intermediate and high risk groups were 86% and 50%, respectively. Side-effects included urethral stricture in 2 of the 16 patients (13%), urinary tract infection or dysuria syndrome in eight (26%), and urinary incontinence in one (6%). Recto-urethral fistula occurred in one patient (6%). Transrectal HIFU is an effective treatment for recurrence after radiotherapy especially in patients with low- and intermediate risk groups.

A pretreatment nomogram for prediction of biochemical failure after primary cryoablation of the prostate.

PubMed

Elshafei, Ahmed; Kovac, Evan; Dhar, Nivedita; Levy, David; Polascik, Thomas; Mouraviev, Vladimir; Yu, Changhong; Jones, J Stephen

2015-09-01

To create a predictive nomogram for biochemical failure following primary whole-gland cryoablation of the prostate for localized prostate cancer (LPCa). We retrospectively analyzed 2,242 patients from the Cryo On-Line Database (COLD) who were treatment naive and had undergone primary whole gland cryoablation of the prostate for biopsy-confirmed LPCa. Kaplan-Meier (KM) curves estimating 5 year biochemical progression-free survival (bPFS) were generated. Multivariable Cox proportional hazards analysis (CoxPH) was performed in order to construct the nomogram. The nomogram was internally validated using the bootstrap technique. Overall, the KM estimated 5 year bPFS was 72.8%. Stratified by D'Amico risk, The KM estimated 5 year bPFS was 82.6%, 71.1%, and 57.8% for low-, intermediate-, and high-risk groups, respectively. Statistically significant predictors of biochemical outcomes from CoxPH analysis were pre-treatment prostate specific antigen (PTPSA) (P < 0.001), total prostate volume (P = 0.004), clinical stage (P = 0.034), and Gleason score (0.004). A nomogram for predicted 5 year biochemical progression free probability was constructed with a concordance index of 0.652. An online risk calculator was also generated. To the best of our knowledge, this is the first predictive nomogram for biochemical outcomes after primary whole gland cryoablation of the prostate using socio-demographic, pretreatment, clinical, and prostate biopsy data. Our nomogram and online risk calculator can guide both patients and urologists for shared decision making regarding definitive treatment options. © 2015 Wiley Periodicals, Inc.

Hypofractionated radiation therapy for prostate cancer: The McGill University Health Center experience.

PubMed

Barbosa Neto, O; Souhami, L; Faria, S

2015-10-01

In 2002, at the McGill University Health Centre, we began a program of hypofractionated radiotherapy for patients with low risk prostate cancer as an alternative to conventionally fractionated radiotherapy. Our initial hypofractionation regimen was 66 Gy given in 22 fractions, prescribed to the isocenter, delivered with 3D-conformal radiotherapy plan. The clinical target volume was the prostate gland and the planning target volume consisted of the clinical target volume plus a 7-mm margin in all directions. Hormonal therapy was not given to any patient. The long-term results for this group of patients confirmed the feasibility, good tolerance and excellent disease control of the regimen with the extra-benefit of being convenient to both patients and the health system by shortening treatment duration. The outcomes of this approach stimulated us to use hypofractionation in patients with intermediate-risk. Analysis of 100 intermediate-risk patients receiving our hypofractionated radiotherapy regimen (no hormones) shows, at median follow-up of 75 months, 8-year biochemical recurrence free and cancer specific survival rates of 90% and 95%, respectively, with acceptable toxicity. Our technique changed from 3D to intensity modulated radiotherapy with the dose adjusted to 60 Gy in 20 fractions. Lastly, we have expanded the program to high-risk patients where IMRT treatments are given to the pelvic nodes (44 Gy in 20 fractions) with a simultaneous integrated boost delivery to the prostate (60 Gy in the same 20 fractions). Our long-term results have shown that moderate hypofractionated radiotherapy for prostate cancer is safe and provides good tumor control comparable to high-dose conventionally fractionated radiotherapy. This hypofractionated regimen has been routinely used in our institution. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Long-term Survival and Toxicity in Patients Treated With High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spratt, Daniel E.; Pei, Xin; Yamada, Josh

2013-03-01

Purpose: To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. Methods and Materials: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified by prognostic risk group based on National Comprehensive Cancer Network risk classification criteria. A total of 587 patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range, 1-14 years). Results: For low-, intermediate-,more » and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This study represents the largest cohort of patients treated with high-dose radiation to 86.4 Gy, using IMRT for localized prostate cancer, with the longest follow-up to date. Our findings indicate that this treatment results in excellent clinical outcomes with acceptable toxicity.« less

Androgen Deprivation Therapy Use in the Setting of High-dose Radiation Therapy and the Risk of Prostate Cancer–Specific Mortality Stratified by the Extent of Competing Mortality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rose, Brent S., E-mail: brose44@gmail.com; Chen, Ming-Hui; Wu, Jing

Purpose: The addition of androgen deprivation therapy (ADT) to radiation therapy (RT) is the standard of care for men with intermediate- and high-risk prostate cancer (PC). However, whether competing mortality (CM) affects the ability of ADT to improve, survival remains unanswered. Methods and Materials: We calculated a CM risk score using a Fine-Gray semiparametric model that included age and cardiometabolic comorbidities from a cohort of 17,669 men treated with high-dose RT with or without supplemental ADT for nonmetastatic PC. Fine and Gray competing risk regression analysis was used to assess whether ADT reduced the risk of PC-specific mortality for menmore » with a low versus a high risk of CM among the 4550 patients within the intermediate- and high-risk cohort after adjustment for established PC prognostic factors, year of treatment, site, and ADT propensity score. Results: After a median follow-up of 8.4 years, 1065 men had died, 89 (8.36%) of PC. Among the men with a low CM score, ADT use was associated with a significant reduction in the risk of PC-specific mortality (adjusted hazard ratio 0.35, 95% confidence interval 0.14-0.87, P=.02) but was not for men with high CM (adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.30, P=.30). Conclusions: Adding ADT to high-dose RT appears to be associated with decreased PC-specific mortality risk in men with a low but not a high CM score. These data should serve to heighten awareness about the importance of considering competing risks when determining whether to add ADT to RT for older men with intermediate- or high-risk PC.« less

Under-utilisation of high-dose-rate brachytherapy boost in men with intermediate-high risk prostate cancer treated with external beam radiotherapy.

PubMed

Ong, Wee Loon; Evans, Sue M; Millar, Jeremy L

2018-04-01

The aim of this study was to evaluate the use of high-dose-rate brachytherapy (HDR-BT) boost with definitive external beam radiotherapy (EBRT) in prostate cancer (CaP) management. The study population comprised men with intermediate-high risk CaP captured in the population-based Prostate Cancer Outcome Registry Victoria (PCOR-Vic), treated with EBRT from January 2010 to December 2015. The primary outcome is the proportion of men who received HDR-BT boost. Multivariate logistic regressions were used to evaluate the effect of patient-, tumour- and treatment-factors on the likelihood of HDR-BT use. Medicare Benefit Schedule (MBS) data was accessed to evaluate the Australia-wide pattern of HDR-BT use. One thousand eight hundred and six patients were included in this study - 886 (49%) intermediate-risk, and 920 (51%) high-risk CaP patients. Overall, only 124 (7%) patients had EBRT + HDR-BT - 47 (5%) intermediate-risk and 77 (8%) high-risk CaP patients (P = 0.01). There is higher proportion of patients who had HDR-BT in public institutions (7% public vs. 3% private, P = 0.005) and in metropolitan centres (9% metropolitan vs. 2% regional, P < 0.001). In multivariate analyses, older patients were less likely to have HDR-BT (OR = 0.92; 95% CI = 0.89-0.94, P < 0.001), while patients with high-risk CaP (OR = 1.8; 95% CI = 1.3-2.7; P = 0.002) treated in metropolitan centres (OR = 5.0; 95% CI = 2.6-9.8; P < 0.001) and public institutions (OR = 3.8; 95% CI = 1.5-9.4; P = 0.005) were more likely to have EBRT + HDR-BT. There was significant decline in numbers of HDR-BT performed throughout Australia, from 313 cases in 2010 to 125 cases in 2015. High-dose-rate brachytherapy is under-utilised with EBRT in this contemporary population-based cohort of Victorian men with CaP. The decline in HDR-BT use was also observed nationally. © 2017 The Royal Australian and New Zealand College of Radiologists.

External beam radiotherapy with dose escalation in 1080 prostate cancer patients: definitive outcome and dose impact.

PubMed

Garibaldi, Elisabetta; Gabriele, Domenico; Maggio, Angelo; Delmastro, Elena; Garibaldi, Monica; Bresciani, Sara; Ortega, Cinzia; Stasi, Michele; Gabriele, Pietro

2016-06-01

The aim of this paper was to report definitive outcome of prostate cancer patients treated with dose escalation during a period of 12.5 years. From October 1999 to March 2012 we treated 1080 patients affected by prostate cancer, using External Beam Radiotherapy (EBRT). The mean age was 69.2 years. Most of the patients (69%) were staged as cT2, Gleason Score (GS)<7; the mean iPSA 18 ng/mL; the rate of clinical positive nodes was 1%. Our intention to treat was the following: for low risk patients 72 Gy; for intermediate risk patients 75.6 Gy and for high-very high risk patients 79.2 Gy in 1.8 Gy/day fractions. From 2008 we changed the fractionation scheme and the doses were the following: for low risk patients 74 Gy and for intermediate and high-very high risk patients 78 Gy in 2.0 Gy/day fractions. Whole pelvis irradiation was performed in high-very high risk patients with 43.2-50.4 Gy in 1.8 Gy per day. The mean follow-up was 81 months. For the whole population at 5 and 10 years, the prostate cancer specific overall survival (CSOS) was 96.7% and 92.2% respectively; the clinical disease free survival (CDFS) 88% and 77%; the biochemical disease free survival (BDFS) 75% and 58.5%. The 5 and 10 years CSOS was 98% and 96% respectively for low risk, 96% and 92% for intermediate risk and 89% and 82% for high-very high risk patients. In intermediate and high-very high risk groups at 5 and 10 years the CSOS was 95.2% and 89.2% respectively, the CDFS 84.5% and 70% and the BDFS 70% and 51% respectively. In high-very high risk patients at 5 and 10 years the CSOS were respectively 89% and 82% the CDFS was 78% and 61% and BDFS was 61% and 34%. In whole patient population the BDFS was related with the dose level (P=0.006) as well as the CDFS (P=0.003) with a cut off of 75.6 Gy. In the subgroup of intermediate plus high-very high risk patients the BDFS and the CDFS were dose-related with a cut off of 75.6 Gy (P=0.007 and P=0.0018 respectively). Finally, in the subgroup of high-very high risk patients we found that the CSOS, the BDFS and the CDFS were related to the dose level with a cut-off of 77.7 Gy (P=0.017; P=0.006 and P=0.038, respectively). Overall gastrointestinal (GI) acute and late G2 toxicities were respectively 5 % and 3.8%; GI acute and late >G3 toxicities were respectively 0.5% and 0.9%; acute and late >G2 genitourinary (GU) toxicities were respectively 10.5% and 2.6%; finally GU acute and late >G3 toxicities were respectively 0.6% and 0.5%. The dose escalation is not relevant for the outcome in low risk patients that can benefit from relatively moderate doses (72-74 Gy). For intermediate and high-very high risk patients the dose becomes significant to levels above 75.6 Gy; particularly in high-very high risk doses >77.7 Gy correlate with an improved outcome. Patients receiving dose >77.7 Gy presented a higher rate of overall GI and GU toxicity, but the number of grade >2 remains low. Our results, consolidated by a long follow-up, corroborate the literature data, confirming that 3D-CRT can allow a safe dose escalation without significantly increasing the severe toxicity.

Disparities in staging prostate magnetic resonance imaging utilization for nonmetastatic prostate cancer patients undergoing definitive radiation therapy.

PubMed

Ajayi, Ayobami; Hwang, Wei-Ting; Vapiwala, Neha; Rosen, Mark; Chapman, Christina H; Both, Stefan; Shah, Meera; Wang, Xingmei; Agawu, Atu; Gabriel, Peter; Christodouleas, John; Tochner, Zelig; Deville, Curtiland

2016-01-01

There is growing evidence supporting incorporating multiparametric (mp) magnetic resonance imaging (MRI) scans into risk stratification, active surveillance, and treatment paradigms for prostate cancer. The purpose of our study was to determine whether demographic disparities exist in staging MRI utilization for prostate cancer patients. An institutional database of 705 nonmetastatic prostate cancer patients treated with radiation therapy from 2005 through 2013 was used to identify patients undergoing versus not undergoing pretreatment diagnostic prostate mpMRI. Uni- and multivariable logistic regression evaluated the relationship of clinical and demographic characteristics with MRI utilization. All demographic variables assessed, except the other race category, were significantly associated with MRI utilization (all P < .05), including age (odds ratio [OR], 0.92), black race (OR, 0.51), poverty (OR, 0.53), closer distance to radiation facility (OR, 1.79), and nonprivate primary insurance (OR, 0.57) on univariable analysis, while clinical stage T3 (OR, 3.37) was the only clinical characteristic. On multivariable analysis stratified by D'Amico risk group, age remained significant across all risk groups, whereas the black versus white racial (OR, 0.21; 95% confidence interval, 0.08-0.55) and nonprivate versus private insurance type (OR, 0.37; 95% confidence interval, 0.16-0.86) disparities persisted in the low-risk group. Clinical stage T3 remained associated in the high-risk group. For race specifically, the percentages of whites, blacks, and others undergoing MRI in the overall cohort and by risk group were, respectively: overall, 80% (343/427), 68% (156/231), and 85% (40/47); low risk, 86%, 56%, and 63%; intermediate risk, 79%, 72%, and 95%; and high risk, 72%, 72%, and 100%. In this urban, academic center cohort, older patients across all risk groups and black or nonprivate insurance patients in the low risk group were less likely to undergo staging prostate MRI scans. Further research should investigate these differences to ensure equitable utilization across all demographic groups considering the burden of prostate cancer disparities.

Primary treatments for clinically localised prostate cancer: a comprehensive lifetime cost-utility analysis.

PubMed

Cooperberg, Matthew R; Ramakrishna, Naren R; Duff, Steven B; Hughes, Kathleen E; Sadownik, Sara; Smith, Joseph A; Tewari, Ashutosh K

2013-03-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Multiple treatment alternatives exist for localised prostate cancer, with few high-quality studies directly comparing their comparative effectiveness and costs. The present study is the most comprehensive cost-effectiveness analysis to date for localised prostate cancer, conducted with a lifetime horizon and accounting for survival, health-related quality-of-life, and cost impact of secondary treatments and other downstream events, as well as primary treatment choices. The analysis found minor differences, generally slightly favouring surgical methods, in quality-adjusted life years across treatment options. However, radiation therapy (RT) was consistently more expensive than surgery, and some alternatives, e.g. intensity-modulated RT for low-risk disease, were dominated - that is, both more expensive and less effective than competing alternatives. To characterise the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (RT: dose-escalated three-dimensional conformal RT, intensity-modulated RT, brachytherapy, or combination), using a comprehensive, lifetime decision analytical model. A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes after primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. In each Markov cycle, patients could have remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the USA payer perspective, with incorporation of patient costs in a sensitivity analysis. Differences across treatments in quality-adjusted life years across methods were modest, ranging from 10.3 to 11.3 for low-risk patients, 9.6-10.5 for intermediate-risk patients and 7.8-9.3 for high-risk patients. There were no statistically significant differences among surgical methods, which tended to be more effective than RT methods, with the exception of combined external beam + brachytherapy for high-risk disease. RT methods were consistently more expensive than surgical methods; costs ranged from $19 901 (robot-assisted prostatectomy for low-risk disease) to $50 276 (combined RT for high-risk disease). These findings were robust to an extensive set of sensitivity analyses. Our analysis found small differences in outcomes and substantial differences in payer and patient costs across treatment alternatives. These findings may inform future policy discussions about strategies to improve efficiency of treatment selection for localised prostate cancer. © 2012 BJU International.

Wide variation of prostate-specific antigen doubling time of untreated, clinically localized, low-to-intermediate grade, prostate carcinoma.

PubMed

Choo, Richard; Klotz, Laurence; Deboer, Gerrit; Danjoux, Cyril; Morton, Gerard C

2004-08-01

To assess the prostate specific antigen (PSA) doubling time of untreated, clinically localized, low-to-intermediate grade prostate carcinoma. A prospective single-arm cohort study has been in progress since November 1995 to assess the feasibility of a watchful-observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The PSA doubling time was estimated from a linear regression of ln(PSA) against time, assuming a simple exponential growth model. As of March 2003, 231 patients had at least 6 months of follow-up (median 45) and at least three PSA measurements (median 8, range 3-21). The distribution of the doubling time was: < 2 years, 26 patients; 2-5 years, 65; 5-10 years, 42; 10-20 years, 26; 20-50 years, 16; >50 years, 56. The median doubling time was 7.0 years; 42% of men had a doubling time of >10 years. The doubling time of untreated clinically localized, low-to-intermediate grade prostate cancer varies widely.

Current clinical presentation and treatment of localized prostate cancer in the United States.

PubMed

Mahmood, Usama; Levy, Lawrence B; Nguyen, Paul L; Lee, Andrew K; Kuban, Deborah A; Hoffman, Karen E

2014-12-01

SEER recently released patient Gleason scores at biopsy/transurethral resection of the prostate. For the first time this permits accurate assessment of prostate cancer presentation and treatment according to clinical factors at diagnosis. We used the SEER database to identify men diagnosed with localized prostate cancer in 2010 who were assigned NCCN(®) risk based on clinical factors. We identified sociodemographic factors associated with high risk disease and analyzed the impact of these factors along with NCCN risk on local treatment. Of the 42,403 men identified disease was high, intermediate and low risk in 38%, 40% and 22%, respectively. On multivariate analysis patients who were older, nonwhite, unmarried or living in a county with a higher poverty rate were more likely to be diagnosed with high risk disease (each p <0.05). Of the 38,634 men in whom prostate cancer was the first malignancy 23% underwent no local treatment, 40% were treated with prostatectomy, 36% received radiation therapy and 1% underwent local tumor destruction, predominantly cryotherapy. On multivariate analysis patients who were older, black, unmarried or living in a county with a higher poverty rate, or who had low risk disease were less likely to receive local treatment (each p <0.05). Our analysis provides information on the current clinical presentation and treatment of localized prostate cancer in the United States. Nonwhite and older men living in a county with a higher poverty rate were more likely to be diagnosed with high risk disease and less likely to receive local treatment. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Favorable Preliminary Outcomes for Men With Low- and Intermediate-risk Prostate Cancer Treated With 19-Gy Single-fraction High-dose-rate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krauss, Daniel J., E-mail: dkrauss@beaumont.edu; Ye, Hong; Martinez, Alvaro A.

Purpose: To report the toxicity and preliminary clinical outcomes of a prospective trial evaluating 19-Gy, single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer. Methods and Materials: A total of 63 patients were treated according to an institutional review board-approved prospective study of single-fraction HDR brachytherapy. Eligible patients had tumor stage ≤T2a, prostate-specific antigen level ≤15 ng/mL, and Gleason score ≤7. Patients with a prostate gland volume >50 cm{sup 3} and baseline American Urologic Association symptom score >12 were ineligible. Patients underwent transrectal ultrasound-guided transperineal implantation of the prostate, followed by single-fraction HDR brachytherapy. Treatment was delivered using {sup 192}Irmore » to a dose of 19 Gy prescribed to the prostate, with no additional margin applied. Results: Of the 63 patients, 58 had data available for analysis. Five patients had withdrawn consent during the follow-up period. The median follow-up period was 2.9 years (range 0.3-5.2). The median age was 61.4 years. The median gland volume at treatment was 34.8 cm{sup 3}. Of the 58 patients, 91% had T1 disease, 71% had Gleason score ≤6 (29% with Gleason score 7), and the median pretreatment prostate-specific antigen level was 5.1 ng/mL. The acute and chronic grade 2 genitourinary toxicity incidence was 12.1% and 10.3%, respectively. No grade 3 urinary toxicity occurred. No patients experienced acute rectal toxicity grade ≥2, and 2 experienced grade ≥2 chronic gastrointestinal toxicity. Three patients experienced biochemical failure, yielding a 3-year cumulative incidence estimate of 6.8%. Conclusions: Single-fraction HDR brachytherapy is well-tolerated, with favorable preliminary biochemical and clinical disease control rates.« less

The evolution of brachytherapy for prostate cancer.

PubMed

Zaorsky, Nicholas G; Davis, Brian J; Nguyen, Paul L; Showalter, Timothy N; Hoskin, Peter J; Yoshioka, Yasuo; Morton, Gerard C; Horwitz, Eric M

2017-06-30

Brachytherapy (BT), using low-dose-rate (LDR) permanent seed implantation or high-dose-rate (HDR) temporary source implantation, is an acceptable treatment option for select patients with prostate cancer of any risk group. The benefits of HDR-BT over LDR-BT include the ability to use the same source for other cancers, lower operator dependence, and - typically - fewer acute irritative symptoms. By contrast, the benefits of LDR-BT include more favourable scheduling logistics, lower initial capital equipment costs, no need for a shielded room, completion in a single implant, and more robust data from clinical trials. Prospective reports comparing HDR-BT and LDR-BT to each other or to other treatment options (such as external beam radiotherapy (EBRT) or surgery) suggest similar outcomes. The 5-year freedom from biochemical failure rates for patients with low-risk, intermediate-risk, and high-risk disease are >85%, 69-97%, and 63-80%, respectively. Brachytherapy with EBRT (versus brachytherapy alone) is an appropriate approach in select patients with intermediate-risk and high-risk disease. The 10-year rates of overall survival, distant metastasis, and cancer-specific mortality are >85%, <10%, and <5%, respectively. Grade 3-4 toxicities associated with HDR-BT and LDR-BT are rare, at <4% in most series, and quality of life is improved in patients who receive brachytherapy compared with those who undergo surgery.

Focal Cryotherapy for Localized Prostate Cancer.

PubMed

Tay, K J; Polascik, T J

2016-07-01

To systematically review the oncological and functional outcomes of contemporary primary prostate focal cryotherapy for localized prostate cancer in the context of current developments in prostate focal therapy. We performed a systematic search of the Pubmed, Cochrane and Embase databases to identify studies where primary prostate focal cryotherapy was performed to treat prostate cancer. These included reports on focal/ lesion/ sector ablation, hemi-ablation and partial prostate ablation. We excluded salvage focal therapy studies. Where multiple reports were published over time from a single cohort, the latest one was used. Our search yielded 290 publications, including 17 primary reports on eight single-center cohort studies and one multi-center registry report. Of 1,595 men identified, mean age was 60.5-69.5 years and mean PSA 5.1-7.8 ng/ml. When stratified by D'Amico risk criteria, 52% of the aggregate total number of men were low-risk, 38% intermediate-risk and 10% high-risk. Besides 12-core TRUS biopsy, 3 cohorts reported using TTMB and one included mpMRI to select men for focal treatment. Median follow-up ranged from 13-63 months. BPFS ranged from 71-98%. The overall post-treatment positive biopsy rate was 8-25%. Among 5 cohorts with a mandatory 6-12 month posttreatment biopsy, 216 of 272 men (79%) did undergo biopsy, with 47 positive (21.8%). Of these, 15 were infield, 26 outfield, 2 bilateral and 4 undeclared. Ten upgraded to Gleason≥7. Overall, two men had metastatic disease and none died of prostate cancer. Post-treatment continence rates were 96-100% and rates of erectile dysfunction ranged from 0-42%. The rate of post-treatment urinary retention ranged from 0-15%. The rate of recto-urethral fistula was 0-0.1%. Focal cryotherapy for localized prostate cancer is a safe and provides good preservation of sexual and urinary function. Accurate cancer localization and risk stratification is key to patient selection. In highly selected patients, focal therapy has good short to medium term oncological efficacy.

Contrast enhanced ultrasound (CEUS) with MRI image fusion for monitoring focal therapy of prostate cancer with high intensity focused ultrasound (HIFU)1.

PubMed

Apfelbeck, M; Clevert, D-A; Ricke, J; Stief, C; Schlenker, B

2018-01-01

Reduced acceptance of radical prostatectomy in patients with low risk or intermediate risk prostate cancer has significantly changed treatment strategies in prostate cancer (PCa) during the last years. Focal therapy of the prostate with high intensity focused ultrasound (HIFU) is an organ-preserving treatment for prostate cancer with less impairment of health-related quality of life. Follow-up after HIFU therapy by imaging modalities remains a major problem as eg. MRI performs poorly. Contrast enhanced ultrasound (CEUS) allows to monitor the vascular architecture of organs non-invasively. However, only limited data are available using CEUS to define successful and complete HIFU treatment of the prostate. In this study, we aimed to evaluate short-term image findings using CEUS and image fusion before and after HIFU treatment. Prospective single arm study in patients with uni- or bilateral, low or intermediate risk prostate cancer or recurrent cancer after radiotherapy treated with HIFU at our institution between October 2016 and November 2017. HIFU hemiablation or whole gland treatment was performed using the Focal One® device. PCa was diagnosed either by multiparametric magnetic resonance imaging (mpMRI) followed by MRI fusion based targeted biopsy combined with 12 core transrectal ultrasound (TRUS) guided biopsy or 12 core random biopsy only. Monitoring of the target region before, immediately and 24 hours after the ablation was done by CEUS in combination with image fusion using an axial T2-weighted MRI sequence. 6 consecutive patients with Gleason score (GS) 6, 5 patients with GS 7a prostate cancer and one patient with biochemical recurrence after radiotherapy were included in the study. Three patients underwent whole gland treatment due to histological proven bilateral PCa or recurrent PCa after radiotherapy. Hemiablation was performed in 9 patients with unilateral tumor and no PIRADS 4 or 5 lesion in the contralateral lobe. Median patient age was 69.8 years and median PSA (prostate-specific antigen) level was 8.4 ng/ml. CEUS showed markedly reduced microbubbles in the ablated area, the prostate capsule still showed signs of perfusion. The study is limited by the short follow up and small number of patients. CEUS examination showed a reduction of microcirculation in the treated area immediately after the treatment and 24 hours later. The combination of CEUS and image fusion seems to be helpful for detecting the PCa target lesion and monitor the success of HIFU ablation treatment. Evidence for image findings after HIFU-therapy are rare. Further studies on this topic are needed.

Perineural invasion is associated with increased relapse after external beam radiotherapy for men with low-risk prostate cancer and may be a marker for occult, high-grade cancer.

PubMed

Beard, C J; Chen, M H; Cote, K; Loffredo, M; Renshaw, A A; Hurwitz, M; D'Amico, A V

2004-01-01

To investigate the risk of postradiotherapy prostate-specific antigen (PSA) failure on the basis of pretreatment risk factors in prostate cancer patients with and without perineural invasion (PNI) in prostate biopsy specimens and to explain the observation that otherwise low-risk patients with PNI experience decreased freedom from PSA failure after external beam radiotherapy (RT). The study cohort consisted of 381 patients who underwent RT between 1989 and 2000 for clinically localized prostate cancer. A single genitourinary pathologist scored the absence or presence of PNI on all prostate biopsy specimens. Patients were divided into low-, intermediate- and high-risk subgroups on the basis of their 1992 American Joint Committee on Cancer T-stage, pretreatment PSA level, and Gleason score. Cox regression uni- and multivariate analyses were performed to evaluate whether the presence or absence of PNI in the biopsy specimen was a predictor of the time to post-RT PSA failure for patients in each pretreatment risk group. PSA failure was defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Actuarial PSA failure-free survival was estimated using the Kaplan-Meier method, and comparisons were performed using the log-rank test. Cox regression univariate analysis revealed that PNI was a significant predictor of the time to PSA failure in the low-risk (p = 0.04) and high-risk (p = 0.03) cohorts. The 5-year PSA failure-free survival rate was 50% vs. 80% (p = 0.04) in low-risk patients, 70% vs. 75% (p = 0.72) in intermediate-risk patients, and 29% vs. 53% (p = 0.03) in high-risk patients with and without PNI, respectively. Cox regression multivariate analysis within the high-risk group revealed that a PSA level > or =20 ng/mL (p = 0.01) and Gleason score > or =8 (p = 0.02), but not PNI, were the only significant predictors of the time to PSA failure after RT. However, an association was found between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 8-10 (p = 0.06). The association was stronger between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 7-10 (p = 0. 033). A decrement in PSA outcome after RT for low-risk patients with PNI-positive biopsy specimens was found. The association between PNI and high Gleason score provides a possible explanation for the loss of statistical significance of PNI in the Cox regression multivariate analysis of the high-risk cohort. The data suggest that PNI found in the biopsy specimen of an otherwise low-risk patient predicts for occult high-grade disease that is missed owing to the sampling error associated with prostate biopsy. The association between PNI and a high Gleason score argues for the use of more aggressive therapy, such as hormonal therapy with RT and/or dose escalation, in these select patients.

A framework to evaluate the cost-effectiveness of the NADiA ProsVue slope to guide adjuvant radiotherapy among men with high-risk characteristics following prostatectomy for prostate cancer.

PubMed

Reed, Shelby D; Stewart, Suzanne Biehn; Scales, Charles D; Moul, Judd W

2014-07-01

The NADiA ProsVue is a prognostic system that measures prostate-specific antigen slope to identify men at lower risk of clinical recurrence of prostate cancer after radical prostatectomy. We developed a decision-modeling framework to evaluate its cost-effectiveness to guide the use of adjuvant radiotherapy (ART). We populated the model using patient-level data and external sources. Patients were classified as intermediate risk or high risk on the basis of Cancer of the Prostate Risk Assessment-Postsurgical (CAPRA-S) nomogram and then stratified by the ProsVue slope (≤2 pg/mL/mo; >2 pg/mL/mo) and receipt of ART. In sensitivity analyses, we varied the effect of the ProsVue slope on the use of ART and other model parameters. The cost-effectiveness of the ProsVue-guided strategy varied widely because of small differences in quality-adjusted life-years (QALYs) at 10 years. In the intermediate-risk group, when the use of ART decreased from 20% (standard care) to 7.5% among patients with a ProsVue slope value of 2 pg/mL/mo or less, the incremental cost-effectiveness ratio was $25,160/QALY. In the high-risk group, the use of ART would have to decrease from 40% (standard care) to 11.5% among those with a ProsVue slope value of 2 pg/mL/mo or less to obtain a ratio of $50,000/QALY. The cost-effectiveness ratios were sensitive to varying benefits of salvage therapy, quality of life, and costs of ART and ProsVue testing. The effect of the ProsVue system on costs will be dependent on the extent to which ART decreases among men identified as having a low risk of recurrence. Its effect on QALYs will remain conditional on uncertain clinical and quality-of-life benefits associated with ART. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Comparative Study of Blood-Based Biomarkers, α2,3-Sialic Acid PSA and PHI, for High-Risk Prostate Cancer Detection.

PubMed

Ferrer-Batallé, Montserrat; Llop, Esther; Ramírez, Manel; Aleixandre, Rosa Núria; Saez, Marc; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

2017-04-17

Prostate Specific Antigen (PSA) is the most commonly used serum marker for prostate cancer (PCa), although it is not specific and sensitive enough to allow the differential diagnosis of the more aggressive tumors. For that, new diagnostic methods are being developed, such as PCA-3, PSA isoforms that have resulted in the 4K score or the Prostate Health Index (PHI), and PSA glycoforms. In the present study, we have compared the PHI with our recently developed PSA glycoform assay, based on the determination of the α2,3-sialic acid percentage of serum PSA (% α2,3-SA), in a cohort of 79 patients, which include 50 PCa of different grades and 29 benign prostate hyperplasia (BPH) patients. The % α2,3-SA could distinguish high-risk PCa patients from the rest of patients better than the PHI (area under the curve (AUC) of 0.971 vs. 0.840), although the PHI correlated better with the Gleason score than the % α2,3-SA. The combination of both markers increased the AUC up to 0.985 resulting in 100% sensitivity and 94.7% specificity to differentiate high-risk PCa from the other low and intermediate-risk PCa and BPH patients. These results suggest that both serum markers complement each other and offer an improved diagnostic tool to identify high-risk PCa, which is an important requirement for guiding treatment decisions.

The Patient-Reported Information Multidimensional Exploration (PRIME) Framework for Investigating Emotions and Other Factors of Prostate Cancer Patients with Low Intermediate Risk Based on Online Cancer Support Group Discussions.

PubMed

Bandaragoda, Tharindu; Ranasinghe, Weranja; Adikari, Achini; de Silva, Daswin; Lawrentschuk, Nathan; Alahakoon, Damminda; Persad, Raj; Bolton, Damien

2018-06-01

This study aimed to use the Patient Reported Information Multidimensional Exploration (PRIME) framework, a novel ensemble of machine-learning and deep-learning algorithms, to extract, analyze, and correlate self-reported information from Online Cancer Support Groups (OCSG) by patients (and partners of patients) with low intermediate-risk prostate cancer (PCa) undergoing radical prostatectomy (RP), external beam radiotherapy (EBRT), and active surveillance (AS), and to investigate its efficacy in quality-of-life (QoL) and emotion measures. From patient-reported information on 10 OCSG, the PRIME framework automatically filtered and extracted conversations on low intermediate-risk PCa with active user participation. Side effects as well as emotional and QoL outcomes for 6084 patients were analyzed. Side-effect profiles differed between the methods analyzed, with men after RP having more urinary and sexual side effects and men after EBRT having more bowel symptoms. Key findings from the analysis of emotional expressions showed that PCa patients younger than 40 years expressed significantly high positive and negative emotions compared with other age groups, that partners of patients expressed more negative emotions than the patients, and that selected cohorts (< 40 years, > 70 years, partners of patients) have frequently used the same terms to express their emotions, which is indicative of QoL issues specific to those cohorts. Despite recent advances in patient-centerd care, patient emotions are largely overlooked, especially in younger men with a diagnosis of PCa and their partners. The authors present a novel approach, the PRIME framework, to extract, analyze, and correlate key patient factors. This framework improves understanding of QoL and identifies low intermediate-risk PCa patients who require additional support.

Pretreatment Endorectal Coil Magnetic Resonance Imaging Findings Predict Biochemical Tumor Control in Prostate Cancer Patients Treated With Combination Brachytherapy and External-Beam Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riaz, Nadeem; Afaq, Asim; Akin, Oguz

Purpose: To investigate the utility of endorectal coil magenetic resonance imaging (eMRI) in predicting biochemical relapse in prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Methods and Materials: Between 2000 and 2008, 279 men with intermediate- or high-risk prostate cancer underwent eMRI of their prostate before receiving brachytherapy and supplemental intensity-modulated radiotherapy. Endorectal coil MRI was performed before treatment and retrospectively reviewed by two radiologists experienced in genitourinary MRI. Image-based variables, including tumor diameter, location, number of sextants involved, and the presence of extracapsular extension (ECE), were incorporated with other established clinical variables to predict biochemical control outcomes.more » The median follow-up was 49 months (range, 1-13 years). Results: The 5-year biochemical relapse-free survival for the cohort was 92%. Clinical findings predicting recurrence on univariate analysis included Gleason score (hazard ratio [HR] 3.6, p = 0.001), PSA (HR 1.04, p = 0.005), and National Comprehensive Cancer Network risk group (HR 4.1, p = 0.002). Clinical T stage and the use of androgen deprivation therapy were not correlated with biochemical failure. Imaging findings on univariate analysis associated with relapse included ECE on MRI (HR 3.79, p = 0.003), tumor size (HR 2.58, p = 0.04), and T stage (HR 1.71, p = 0.004). On multivariate analysis incorporating both clinical and imaging findings, only ECE on MRI and Gleason score were independent predictors of recurrence. Conclusions: Pretreatment eMRI findings predict for biochemical recurrence in intermediate- and high-risk prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Gleason score and the presence of ECE on MRI were the only significant predictors of biochemical relapse in this group of patients.« less

BPH: a tell-tale sign of prostate cancer? Results from the Prostate Cancer and Environment Study (PROtEuS).

PubMed

Boehm, Katharina; Valdivieso, Roger; Meskawi, Malek; Larcher, Alessandro; Sun, Maxine; Sosa, José; Blanc-Lapierre, Audrey; Weiss, Deborah; Graefen, Markus; Saad, Fred; Parent, Marie-Élise; Karakiewicz, Pierre I

2015-12-01

In a population-based case-control study (PROtEuS), we examined the association between prostate cancer (PCa) and (1) benign prostatic hypertrophy (BPH) history at any time prior to PCa diagnosis, (2) BPH-history reported at least 1 year prior to interview/diagnosis (index date) and (3) exposure to BPH-medications. Cases were 1933 men with incident prostate cancer diagnosed across Montreal French hospitals between 2005 and 2009. Population controls were 1994 men from the same age distribution and residential area. In-person interviews collected socio-demographic characteristics and medical history, e.g., BPH diagnosis, duration and treatment, as well as on PCa screening. Logistic regression analyses tested overall and grade-specific associations, including subgroup analyses with frequent PSA testing. A BPH-history was associated with an increased risk of PCa (OR 1.37 [95 % CI 1.16-2.61]), more pronounced for low-grade PCa (Gleason ≤6: OR 1.54 [1.26-1.87]; Gleason ≥7: OR 1.05 [0.86-1.27]). The association was not significant when BPH-history diagnosis was more than 1 year prior to index date, except for low-grade PCa (OR 1.29 [1.05-1.60]). Exposure to 5α reductase inhibitors (5α-RI) resulted in a decreased risk of overall PCa (OR 0.62 [0.42-0.92]), particularly for intermediate- to high-grade PCa (Gleason ≤6: OR 0.70 [0.43-1.14]; Gleason ≥7: OR 0.43 [0.26-0.72]). Adjusting for PSA testing frequency or restricting analyses to frequently screened subjects did not affect these results. BPH-history was associated with an increased PCa risk, which disappeared, when BPH-history did not include BPH diagnosis within the previous year. Our results also suggest that 5α-RI exposure exerts a protective effect on intermediate and high-grade PCa.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaffer, Richard, E-mail: rickyshaffer@yahoo.co.u; Department of Clinical Oncology, Imperial College London National Health Service Trust, London; Pickles, Tom

Purpose: Prior studies have derived low values of alpha-beta ratio (a/ss) for prostate cancer of approximately 1-2 Gy. These studies used poorly matched groups, differing definitions of biochemical failure, and insufficient follow-up. Methods and Materials: National Comprehensive Cancer Network low- or low-intermediate risk prostate cancer patients, treated with external beam radiotherapy or permanent prostate brachytherapy, were matched for prostate-specific antigen, Gleason score, T-stage, percentage of positive cores, androgen deprivation therapy, and era, yielding 118 patient pairs. The Phoenix definition of biochemical failure was used. The best-fitting value for a/ss was found for up to 90-month follow-up using maximum likelihood analysis,more » and the 95% confidence interval using the profile likelihood method. Linear quadratic formalism was applied with the radiobiological parameters of relative biological effectiveness = 1.0, potential doubling time = 45 days, and repair half-time = 1 hour. Bootstrap analysis was performed to estimate uncertainties in outcomes, and hence in a/ss. Sensitivity analysis was performed by varying the values of the radiobiological parameters to extreme values. Results: The value of a/ss best fitting the outcomes data was >30 Gy, with lower 95% confidence limit of 5.2 Gy. This was confirmed on bootstrap analysis. Varying parameters to extreme values still yielded best-fit a/ss of >30 Gy, although the lower 95% confidence interval limit was reduced to 0.6 Gy. Conclusions: Using carefully matched groups, long follow-up, the Phoenix definition of biochemical failure, and well-established statistical methods, the best estimate of a/ss for low and low-tier intermediate-risk prostate cancer is likely to be higher than that of normal tissues, although a low value cannot be excluded.« less

Longitudinal regret after treatment for low- and intermediate-risk prostate cancer.

PubMed

Hurwitz, Lauren M; Cullen, Jennifer; Kim, Daniel J; Elsamanoudi, Sally; Hudak, Jane; Colston, Maryellen; Travis, Judith; Kuo, Huai-Ching; Rice, Kevin R; Porter, Christopher R; Rosner, Inger L

2017-11-01

Prostate cancer patients diagnosed with low- and intermediate-risk disease have several treatment options. Decisional regret after treatment is a concern, especially when poor oncologic outcomes or declines in health-related quality of life (HRQoL) occur. This study assessed determinants of longitudinal decisional regret in prostate cancer patients attending a multidisciplinary clinic and treated with radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy (BT), or active surveillance (AS). Patients newly diagnosed with prostate cancer at the Walter Reed National Military Medical Center who attended a multidisciplinary clinic were enrolled into a prospective study from 2006 to 2014. The Decision Regret Scale was administered at 6, 12, 24, and 36 months posttreatment. HRQoL was also assessed at regular intervals using the Expanded Prostate Cancer Index Composite and 36-item RAND Medical Outcomes Study Short Form questionnaires. Adjusted probabilities of reporting regret were estimated via multivariable logistic regression fitted with generalized estimating equations. A total of 652 patients met the inclusion criteria (395 RP, 141 EBRT, 41 BT, 75 AS). Decisional regret was consistently low after all of these treatments. In multivariable models, only African American race (odds ratio, 1.67; 95% confidence interval, 1.12-2.47) was associated with greater regret across time. Age and control preference were marginally associated with regret. Regret scores were similar between RP patients who did and did not experience biochemical recurrence. Declines in HRQoL were weakly correlated with greater decisional regret. In the context of a multidisciplinary clinic, decisional regret did not differ significantly between treatment groups but was greater in African Americans and those reporting poorer HRQoL. Cancer 2017;123:4252-4258. © 2017 American Cancer Society. © 2017 American Cancer Society.

Hypofractionated Volumetric Modulated Arc Radiotherapy with simultaneous Elective Nodal Irradiation is feasible in prostate cancer patients: A single institution experience.

PubMed

Hegazy, Mohamed W; Mahmood, Rana I; Al Otaibi, Mohammed F; Khalil, Ehab M

2016-06-01

To assess feasibility, toxicity and biochemical relapse-free survival (b-RFS) for a group of organ confined (OC) Saudi prostate cancer patients treated by hypo-fractionated Volumetric Modulated Arc Radiation Therapy (VMAT) Simultaneous Integrated Boost (SIB) Elective Nodal Irradiation (ENI) whole pelvic radiotherapy (WPRT). Between March 2009 and January 2014, 29 OC prostate cancer patients; median age 64years, PS 0-1 were treated in King Faisal Specialist Hospital - Riyadh, Kingdom of Saudi Arabia using VMAT-SIB-ENI-WPRT, to a total dose of 70Gy in 28 fractions. Twenty Four patients (83%) were treated with neo-adjuvant; concurrent androgen deprivation therapy (ADT). Median follow-up (FU) was 42months (range: 18-72months). The 3-year actuarial b-RFS for low/intermediate and high risk groups were 100%, and 48%, respectively (p=0.09) with a median FU period of 34months (range: 14-53months). Gleason Score (p=0.02), and pretreatment PSA (p=0.01) were predictive for biochemical failure on univariate analysis; with no observed prostate cancer-related deaths. Grade 2 acute/late GI and GU toxicities were 28%/0% and 17%/10% respectively with no reported grade 3/4 toxicities. Four (50%) out of the 8 patients with baseline partial potency, retained sexual function on long term follow-up. Hypo-fractionation dose escalation VMAT-SIB-ENI-WPRT using 2 arcs is a feasible technique for intermediate/high risk OC prostate cancer patients, with acceptable rates of acute/late toxicities, much favorable planning target volume (PTV) coverage, and shorter overall treatment time. Prospective randomized controlled trials are encouraged to confirm its equivalence to other fractionation schemes. Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Phase I study of replication-competent adenovirus-mediated double-suicide gene therapy in combination with conventional-dose three-dimensional conformal radiation therapy for the treatment of newly diagnosed, intermediate- to high-risk prostate cancer.

PubMed

Freytag, Svend O; Stricker, Hans; Pegg, Jan; Paielli, Dell; Pradhan, Deepak G; Peabody, James; DePeralta-Venturina, Mariza; Xia, Xueqing; Brown, Steve; Lu, Mei; Kim, Jae Ho

2003-11-01

The primary study objective was to determine the safety of intraprostatic administration of a replication-competent, oncolytic adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene concomitant with increasing durations of 5-fluorocytosine and valganciclovir prodrug therapy and conventional-dose three-dimensional conformal radiation therapy (3D-CRT) in patients with newly diagnosed, intermediate- to high-risk prostate cancer. Secondary objectives were to determine the persistence of therapeutic transgene expression in the prostate and to examine early posttreatment response. Fifteen patients in five cohorts received a single intraprostatic injection of 10(12) viral particles of the replication-competent Ad5-CD/TKrep adenovirus on day 1. Two days later, patients were administered 5-fluorocytosine and valganciclovir prodrug therapy for 1 (cohorts 1-3), 2 (cohort 4), or 3 (cohort 5) weeks along with 70-74 Gy 3D-CRT. Sextant needle biopsy of the prostate was obtained at 2 (cohort 1), 3 (cohort 2), and 4 (cohort 3) weeks for determination of the persistence of transgene expression. There were no dose-limiting toxicities and no significant treatment-related adverse events. Ninety-four percent of the adverse events observed were mild to moderate and self-limiting. Acute urinary and gastrointestinal toxicities were similar to those expected for conventional-dose 3D-CRT. Therapeutic transgene expression was found to persist in the prostate for up to 3 weeks after the adenovirus injection. As expected for patients receiving definitive radiation therapy, all patients experienced significant declines in prostate-specific antigen (PSA). The mean PSA half-life in patients administered more than 1 week of prodrug therapy was significantly shorter than that of patients receiving prodrugs for only 1 week (0.6 versus 2.0 months; P < 0.02) and markedly shorter than that reported previously for patients treated with conventional-dose 3D-CRT alone (2.4 months). With a median follow-up of only 9 months, 5 of 10 (50%) patients not treated with androgen-deprivation therapy achieved a serum PSA < or = 0.5 ng/ml. The results demonstrate that replication-competent adenovirus-mediated double-suicide gene therapy can be combined safely with conventional-dose 3D-CRT in patients with intermediate- to high-risk prostate cancer. The shorter than expected PSA half-life in patients receiving more than 1 week of prodrug therapy may suggest a possible interaction between the oncolytic adenovirus and/or double-suicide gene therapies and radiation therapy.

Synthetic Lethality as a Targeted Approach to Advanced Prostate Cancer

DTIC Science & Technology

2014-05-01

syndrome (MDS) [36-41]. Multiple Phase III trials of tipifarnib monotherapy in acute myeloid leukemia (AML) and in refractory advanced colorectal...cytarabine for patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome . Cancer 2011;117(6):1236-44 42. Harousseau JL...multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome . Blood 2007;109(10):4158

Genomic and Histopathological Tissue Biomarkers That Predict Radiotherapy Response in Localised Prostate Cancer

PubMed Central

Wilkins, Anna; Dearnaley, David; Somaiah, Navita

2015-01-01

Localised prostate cancer, in particular, intermediate risk disease, has varied survival outcomes that cannot be predicted accurately using current clinical risk factors. External beam radiotherapy (EBRT) is one of the standard curative treatment options for localised disease and its efficacy is related to wide ranging aspects of tumour biology. Histopathological techniques including immunohistochemistry and a variety of genomic assays have been used to identify biomarkers of tumour proliferation, cell cycle checkpoints, hypoxia, DNA repair, apoptosis, and androgen synthesis, which predict response to radiotherapy. Global measures of genomic instability also show exciting capacity to predict survival outcomes following EBRT. There is also an urgent clinical need for biomarkers to predict the radiotherapy fraction sensitivity of different prostate tumours and preclinical studies point to possible candidates. Finally, the increased resolution of next generation sequencing (NGS) is likely to enable yet more precise molecular predictions of radiotherapy response and fraction sensitivity. PMID:26504789

Direct 2-Arm Comparison Shows Benefit of High-Dose-Rate Brachytherapy Boost vs External Beam Radiation Therapy Alone for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khor, Richard; Duchesne, Gillian; Monash University, Melbourne

Purpose: To evaluate the outcomes of patients treated for intermediate- and high-risk prostate cancer with a single schedule of either external beam radiation therapy (EBRT) and high-dose-rate brachytherapy (HDRB) boost or EBRT alone. Methods and Materials: From 2001-2006, 344 patients received EBRT with HDRB boost for definitive treatment of intermediate- or high-risk prostate cancer. The prescribed EBRT dose was 46 Gy in 23 fractions, with a HDR boost of 19.5 Gy in 3 fractions. This cohort was compared to a contemporaneously treated cohort who received EBRT to 74 Gy in 37 fractions, using a matched pair analysis. Three-dimensional conformal EBRTmore » was used. Matching was performed using a propensity score matching technique. High-risk patients constituted 41% of the matched cohorts. Five-year clinical and biochemical outcomes were analyzed. Results: Initial significant differences in prognostic indicators between the unmatched treatment cohorts were rendered negligible after matching, providing a total of 688 patients. Median biochemical follow-up was 60.5 months. The 5-year freedom from biochemical failure was 79.8% (95% confidence interval [CI], 74.3%-85.0%) and 70.9% (95% CI, 65.4%-76.0%) for the HDRB and EBRT groups, respectively, equating to a hazard ratio of 0.59 (95% CI, 0.43-0.81, P=.0011). Interaction analyses showed no alteration in HDR efficacy when planned androgen deprivation therapy was administered (P=.95), but a strong trend toward reduced efficacy was shown compared to EBRT in high-risk cases (P=.06). Rates of grade 3 urethral stricture were 0.3% (95% CI, 0%-0.9%) and 11.8% (95% CI, 8.1%-16.5%) for EBRT and HDRB, respectively (P<.0001). No differences in clinical outcomes were observed. Conclusions: This comparison of 2 individual contemporaneously treated HDRB and EBRT approaches showed improved freedom from biochemical progression with the HDR approach. The benefit was more pronounced in intermediate- risk patients but needs to be weighed against an increased risk of urethral toxicity.« less

Performance of 68Ga-PSMA PET/CT for Prostate Cancer Management at Initial Staging and Time of Biochemical Recurrence.

PubMed

Bailey, Jason; Piert, Morand

2017-09-09

Recently introduced Gallium-68 labeled PSMA-ligands such as HBED-CC ( 68 Ga-PSMA) have shown promise for unmet diagnostic needs in prostate cancer. 68 Ga-PSMA has demonstrated improved detection rates and specificity for prostate cancer compared to standard imaging approaches. In the setting of primary disease, 68 Ga-PSMA appears to preferentially identify treatment-relevant intermediate and high-risk prostate cancer. There is also a growing evidence that 68 Ga-PSMA positron emission tomography (PET) outperforms alternative conventional imaging methods including choline-based radiotracers for the localization of disease sites at biochemical recurrence, particularly at lower prostate-specific antigen (PSA) levels (< 1 ng/mL). However, the majority of published work lacks rigorous verification of imaging results. 68 Ga-PSMA offers significant promise for both, primary disease and biochemically recurrent prostate cancer. The evidence base to support 68 Ga-PSMA is however still underdeveloped, and more rigorous studies substantiating efficacy are needed.

Integration of Diagnostic and Interventional MRI for the Study of Persistent Prostate Cancer after External Beam Radiotherapy

DTIC Science & Technology

2009-10-01

1500 ms). A clinical pilot study reported equivalence between central gland (CG) and peripheral zone (PZ) T1 values (CG: 1321±45 ms, n=14; PZ: 1359...across variable TI, the period of longitudinal recovery is kept independent of TI selection for any TR. Central to T1prep is RF cycling of an...pilot study A clinical pilot study involved 15 patients with low or intermediate risk localized prostate cancer and no history of prior therapy. The

Growth Of High-Cost Intensity-Modulated Radiotherapy For Prostate Cancer Raises Concerns About Overuse

PubMed Central

Jacobs, Bruce L.; Zhang, Yun; Skolarus, Ted A.; Hollenbeck, Brent K.

2012-01-01

To study the impact of new, expensive, and unproven therapies to treat prostate cancer, we investigated the dissemination of intensity-modulated radiotherapy (IMRT). IMRT is an innovative treatment for prostate cancer that delivers higher doses of radiation with improved precision compared to alternative radiotherapies. We observed rapid adoption of this new treatment among men diagnosed with prostate cancer from 2001 through 2007, despite uncertainty about its relative effectiveness. We compared patient and disease characteristics of those receiving IMRT and the previous radiation standard of care, three-dimensional conformal therapy; assessed intermediate-term outcomes; and examined potential factors associated with the increased use of IMRT. We found that in the early period of IMRT adoption (2001–03) men with high-risk disease were more likely to receive IMRT, whereas after IMRT’s initial dissemination (2004–07) men with low-risk disease had fairly similar likelihoods of receiving IMRT as men with high-risk disease. This raises concerns about overtreatment, as well as considerable health care costs, because treatment with IMRT costs $15,000–$20,000 more than other standard therapies. As health care delivery reforms gain traction, policy makers must balance the promotion of new, yet unproven, technology with the risk of overuse. PMID:22492892

Erectile Function and Oncologic Outcomes Following Open Retropubic and Robot-assisted Radical Prostatectomy: Results from the LAParoscopic Prostatectomy Robot Open Trial.

PubMed

Sooriakumaran, Prasanna; Pini, Giovannalberto; Nyberg, Tommy; Derogar, Maryam; Carlsson, Stefan; Stranne, Johan; Bjartell, Anders; Hugosson, Jonas; Steineck, Gunnar; Wiklund, Peter N

2018-04-01

Whether surgeons perform better utilising a robot-assisted laparoscopic technique compared with an open approach during prostate cancer surgery is debatable. To report erectile function and early oncologic outcomes for both surgical modalities, stratified by prostate cancer risk grouping. In a prospective nonrandomised trial, we recruited 2545 men with prostate cancer from seven open (n=753) and seven robot-assisted (n=1792) Swedish centres (2008-2011). Clinometrically-validated questionnaire-based patient-reported erectile function was collected before, 3 mo, 12 mo, and 24 mo after surgery. Surgeon-reported degree of neurovascular-bundle preservation, pathologist-reported positive surgical margin (PSM) rates, and 2-yr prostate-specific antigen-relapse rates were measured. Among 1702 preoperatively potent men, we found enhanced erectile function recovery for low/intermediate-risk patients in the robot-assisted group at 3 mo. For patients with high-risk tumours, point estimates for erectile function recovery at 24 mo favoured the open surgery group. The degree of neurovascular bundle preservation and erectile function recovery were greater correlated for robot-assisted surgery. In pT2 tumours, 10% versus 17% PSM rates were observed for open and robot-assisted surgery, respectively; corresponding rates for pT3 tumours were 48% and 33%. These differences were associated with biochemical recurrence in pT3 but not pT2 disease. The study is limited by its nonrandomised design and relatively short follow-up. Earlier recovery of erectile function in the robot-assisted surgery group in lower-risk patients is counterbalanced by lower PSM rates for open surgeons in organ-confined disease; thus, both open and robotic surgeons need to consider this trade-off when determining the plane of surgical dissection. Robot-assisted surgery also facilitates easier identification of nerve preservation planes during radical prostatectomy as well as wider dissection for pT3 cases. For prostate cancer surgery, an open operation reduces erection problems in high-risk cancers but has higher relapse rates than robotic surgery. Relapse rates appear similar in low/intermediate-risk cancers and the robot appears better at preserving erections in these cases. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Radical Prostatectomy versus Observation for Localized Prostate Cancer

PubMed Central

Wilt, Timothy J.; Brawer, Michael K.; Jones, Karen M.; Barry, Michael J.; Aronson, William J.; Fox, Steven; Gingrich, Jeffrey R.; Wei, John T.; Gilhooly, Patricia; Grob, B. Mayer; Nsouli, Imad; Iyer, Padmini; Cartagena, Ruben; Snider, Glenn; Roehrborn, Claus; Sharifi, Roohollah; Blank, William; Pandya, Parikshit; Andriole, Gerald L.; Culkin, Daniel; Wheeler, Thomas

2012-01-01

BACKGROUND The effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known. METHODS From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality. RESULTS During the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P = 0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P = 0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P = 0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P = 0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death. CONCLUSIONS Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials.gov number, NCT00007644.) PMID:22808955

High-Dose-Rate Monotherapy for Localized Prostate Cancer: 10-Year Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hauswald, Henrik; Kamrava, Mitchell R.; Fallon, Julia M.

2016-03-15

Purpose: High-dose-rate (HDR) brachytherapy was originally used with external beam radiation therapy (EBRT) to increase the dose to the prostate without injuring the bladder or rectum. Numerous studies have reported HDR brachytherapy is safe and effective. We adapted it for use without EBRT for cases not requiring lymph node treatment. Patients and Methods: We entered the patient demographics, disease characteristics, and treatment parameters into a prospective registry and serially added follow-up data for 448 men with low-risk (n=288) and intermediate-risk (n=160) prostate cancer treated from 1996 to 2009. Their median age was 64 years (range 42-90). The median prostate-specific antigen (PSA)more » level was 6.0 ng/mL (range 0.2-18.2). The Gleason score was ≤6 in 76% and 7 in 24%. The median dose was 43.5 Gy in 6 fractions. The clinical and biochemical disease control and survival rates were calculated. Adverse events were graded according to the Common Toxicity Criteria of Adverse Events. Results: The median follow-up period was 6.5 years (range 0.3-15.3). The actuarial 6- and 10-year PSA progression-free survival was 98.6% (95% confidence interval [CI] 96.9%-99.4%) and 97.8% (95% CI 95.5%-98.9%). Overall survival at 10 years was 76.7% (95% CI 69.9%-82.2%). The local control, distant metastasis-free survival, and cause-specific survival were 99.7% (95% CI 97.9%-99.9%), 98.9% (95% CI 96.3%-99.7%), and 99.1% (95% CI 95.8%-99.8%). T stage, initial PSA level, Gleason score, National Comprehensive Cancer Network risk group, patient age, and androgen deprivation therapy did not significantly correlate with disease control or survival. No late grade 3 to 4 rectal toxicities developed. Late grade 3 to 4 genitourinary toxicity occurred in 4.9% (grade 3 in 4.7%). Conclusions: HDR monotherapy is a safe and highly effective treatment of low- and intermediate-risk prostate cancer.« less

Meat consumption, Cooking Practices, Meat Mutagens and Risk of Prostate Cancer

PubMed Central

John, Esther M.; Stern, Mariana C.; Sinha, Rashmi; Koo, Jocelyn

2012-01-01

Consumption of red meat, particularly well done meat, has been associated with increased prostate cancer risk. High temperature cooking methods such as grilling and barbequeing may produce heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) which are known carcinogens. We assessed the association with meat consumption and estimated HCA and PAH exposure in a population-based case-control study of prostate cancer. Newly diagnosed cases aged 40–79 years (531 advanced cases, 195 localized cases) and 527 controls were asked about dietary intake, including usual meat cooking methods and doneness levels. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression. For advanced prostate cancer, but not localized disease, increased risks were associated with higher consumption of hamburgers (OR=1.79. CI=1.10–2.92), processed meat (OR=1.57, CI=1.04, 2.36), grilled red meat (OR=1.63, CI=0.99–2.68), and well done red meat (OR=1.52, CI=0.93–2.46), and intermediate intake of 2-amino-1-methyl1-6-phenylimidazo[4,5-b]pyridine (PhIP) (quartile 2 vs. 1: OR=1.41, CI=0.98–2.01; quartile 3 vs. 1: OR=1.42, CI=0.98–2.04), but not for higher intake. White meat consumption was not associated with prostate cancer. These findings provide further evidence that consumption of processed meat and red meat cooked at high temperature is associated with increased risk of advanced, but not localized prostate cancer. PMID:21526454

Impact of distance to a urologist on early diagnosis of prostate cancer among black and white patients.

PubMed

Holmes, Jordan A; Carpenter, William R; Wu, Yang; Hendrix, Laura H; Peacock, Sharon; Massing, Mark; Schenck, Anna P; Meyer, Anne-Marie; Diao, Kevin; Wheeler, Stephanie B; Godley, Paul A; Stitzenberg, Karyn B; Chen, Ronald C

2012-03-01

We examined whether an increased distance to a urologist is associated with a delayed diagnosis of prostate cancer among black and white patients, as manifested by higher risk disease at diagnosis. North Carolina Central Cancer Registry data were linked to Medicare claims for patients with incident prostate cancer diagnosed in 2004 to 2005. Straight-line distances were calculated from the patient home to the nearest urologist. Race stratified multivariate ordinal logistic regression was used to examine the association between distance to a urologist and prostate cancer risk group (low, intermediate, high or very high/metastasis) at diagnosis for black and white patients while accounting for age, comorbidity, marital status and diagnosis year. An overall model was then used to examine the distance × race interaction effect. Included in analysis were 1,720 white and 531 black men. In the overall cohort the high risk cancer rate increased monotonically with distance to a urologist, including 40% for 0 to 10, 45% for 11 to 20 and 57% for greater than 20 miles. Correspondingly the low risk cancer rate decreased with longer distance. On race stratified multivariate analysis longer distance was associated with higher risk prostate cancer for white and black patients (p = 0.04 and <0.01, respectively) but the effect was larger in the latter group. The distance × race interaction term was significant in the overall model (p = 0.03). Longer distance to a urologist may disproportionally impact black patients. Decreasing modifiable barriers to health care access, such as distance to care, may decrease racial disparities in prostate cancer. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Time-driven activity-based cost comparison of prostate cancer brachytherapy and intensity-modulated radiation therapy.

PubMed

Dutta, Sunil W; Bauer-Nilsen, Kristine; Sanders, Jason C; Trifiletti, Daniel M; Libby, Bruce; Lash, Donna H; Lain, Melody; Christodoulou, Deborah; Hodge, Constance; Showalter, Timothy N

To evaluate the delivery cost of frequently used radiotherapy options offered to patients with intermediate- to high-risk prostate cancer using time-driven activity-based costing and compare the results with Medicare reimbursement and relative value units (RVUs). Process maps were created to represent each step of prostate radiotherapy treatment at our institution. Salary data, equipment purchase costs, and consumable costs were factored into the cost analysis. The capacity cost rate was determined for each resource and calculated for each treatment option from initial consultation to its completion. Treatment options included low-dose-rate brachytherapy (LDR-BT), combined high-dose-rate brachytherapy single fraction boost with 25-fraction intensity-modulated radiotherapy (HDR-BT-IMRT), moderately hypofractionated 28-fraction IMRT, conventionally fractionated 39-fraction IMRT, and conventionally fractionated (2 Gy/fraction) 23-fraction pelvis irradiation with 16-fraction prostate boost. The total cost to deliver LDR-BT, HDR-BT-IMRT, moderately hypofractionated 28-fraction IMRT, conventionally fractionated 39-fraction IMRT, conventionally fractionated 39-fraction IMRT, and conventionally fractionated (2 Gy/fraction) 23-fraction pelvis irradiation with 16-fraction prostate boost was $2719, $6517, $4173, $5507, and $5663, respectively. Total reimbursement for each course was $3123, $10,156, $7862, $9725, and $10,377, respectively. Radiation oncology attending time was 1.5-2 times higher for treatment courses incorporating BT. Attending radiation oncologist's time consumed per RVU was higher with BT (4.83 and 2.56 minutes per RVU generated for LDR-BT and HDR-BT-IMRT, respectively) compared to without BT (1.41-1.62 minutes per RVU). Time-driven activity-based costing analysis identified higher delivery costs associated with prostate BT compared with IMRT alone. In light of recent guidelines promoting BT for intermediate- to high-risk disease, re-evaluation of payment policies is warranted to encourage BT delivery. Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Ten-year Biochemical Disease-free Survival After High-intensity Focused Ultrasound (HIFU) for Localized Prostate Cancer: Comparison with Four Different Generation Devices

NASA Astrophysics Data System (ADS)

Uchida, T.; Nakano, M.; Shoji, S.; Omata, T.; Harano, Y.; Nagata, Y.; Usui, Y.; Terachi, T.

2010-03-01

HIFU has been recognized as a minimally invasive treatment option for localized prostate cancer. The purpose of the study was to assess with a long-term outcome of HIFU for prostate cancer. From January 1999, a total of 657 patients who had HIFU with at least 2 year follow-up were treated with four different types of Sonablate® (Focus Surgery, Indianapolis, USA) devices. Thirty-three patients were treated with Sonablate® 200 (S200) from 1999 to 2001, 406 patients with Sonablate® 500 (S500) from 2001 to 2005, 200 patients with Sonablate® 500 version 4 (V4) from 2005-2008 and 19 patients with Sonablate® 500 TCM (TCM) from 2007. Biochemical disease-free survival rate (bDFS) in all patients was 59% in 8 years. bDFS in 8 years in patients with S200 and S500 groups were 55% and 56%, and bDFS in 4 and 2 years in patients with V4 and TCM group were 72% and 84%, respectively. bDFS in low, intermediate, and high risk groups were 75%, 54%, and 43% in S200/S500 and 93%, 72%, and 58% in V4/TCM group. Negative prostate biopsy rate after HIFU was 97% in S200, 79% in S500, 94% in V4 and 100% in TCM group. HIFU as primary therapy for prostate cancer is indicated in patients with low- and intermediate-risk (T1-T2b N0M0 disease, a Gleason score of ⩽7, a PSA level of <20 ng/mL) and a prostate volume of less than 40 mL. The rate of clinical outcome has significantly improved over the years due to technical improvements in the device.

Effect of family history on outcomes in patients treated with definitive brachytherapy for clinically localized prostate cancer.

PubMed

Peters, Christopher A; Stock, Richard G; Blacksburg, Seth R; Stone, Nelson N

2009-01-01

To determine the impact familial prostate cancer has on prognosis in men treated with brachytherapy for clinically localized prostate cancer. A total of 1,738 consecutive patients with prostate cancer (cT1-3, N0/X, M0) received low-dose-rate brachytherapy alone or in combination with external beam radiation therapy or hormone ablation from 1992 to 2005. The primary end-point was freedom from biochemical failure (FFBF) using the Phoenix definition. Minimum follow-up was 2 years and the median follow-up was 60 months (range, 24-197 months). A total of 187 of 1,738 men (11%) had a family history of prostate cancer in a first-degree relative. For the low-risk patients, both groups had similar actuarial 5-year FFBF (97.2% vs. 95.5%, p = 0.516). For intermediate-risk patients, there was a trend toward improved biochemical control in men positive for family history (5-yr FFBF 100% vs. 93.6%, p = 0.076). For the high-risk patients, men with a positive family history had similar 5-year FFBF (92.8% vs. 85.2%, p = 0.124). On multivariate analysis, family history was not significant; use of hormones, high biologic effective dose, initial prostate-specific antigen value, and Gleason score were the significant variables predicting biochemical control. This is the first study to examine the relationship of familial prostate cancer and outcomed in men treated with brachytherapy alone or in combination therapy. Men with a positive family history have clinicopathologic characteristics and biochemical outcomes similar to those with sporadic disease.

Salvage High-intensity Focused Ultrasound for the Recurrent Prostate Cancer after Radiotherapy in Japan

NASA Astrophysics Data System (ADS)

Shoji, S.; Nakano, M.; Nagata, Y.; Uchida, T.

2011-09-01

To investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 20 cases treated using the Sonablate® 500 HIFU device, between August 28, 2002 and June 1, 2010, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. The mean (range) age was 65 (52-80) years with a mean PSA level before radiation therapy of 26.6 (4.8-118) ng/mL. The mean (range) period after radiation therapy to HIFU was 41 (4-96) months. All men with presumed, organ-confined, recurrent disease following EBRT in 13 patients, brachytherapy in 5 patients (4 patients with high-dose brachytherapy with In192 and 1 with low-dose brachytherapy with Au98) or proton therapy in 4 patients treated with salvage HIFU were included. The patients were followed for a mean (range) of 21 months. Biochemical disease-free survival (bDFS) rates in patients with low-, intermediate- and high risk groups were 100%, 85.7%, and 18.2%, respectively. All nine patients who received a post HIFU prostate biopsy showed no malignancy. Side-effects included urethral stricture in 4 of the 22 patients (18%) and urinary incontinence in 4 of the 22 patients (18%). Recto-urethral fistula occurred in one patient (5%). Salvage HIFU is a minimally invasive for patients with low-and intermediate risk group with comparable morbidity to other forms of salvage treatment.

Salvage high-intensity focused ultrasound for the recurrent prostate cancer after radiotherapy in Japan

NASA Astrophysics Data System (ADS)

Shoji, S.; Nakano, M.; Nagata, Y.; Uchida, T.

2012-10-01

Aim: to investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 22 cases treated using the Sonablate® 500 HIFU device, between August 28, 2002 and April 1, 2010, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. The mean (range) age was 65 (52-80) years with a mean PSA level before radiation therapy of 14.3 (5.7-118) ng/mL. The mean (range) period after radiation therapy to HIFU was 36 (4-96) months. All men with presumed, organ-confined, recurrent disease following EBRT in 14 patients, brachytherapy in 5 patients (4 patients with high-dose brachytherapy with In192 and 1 with low-dose brachytherapy with Au98) or proton therapy in 3 patients treated with salvage HIFU were included. The patients were followed for a mean (range) of 24 months. Biochemical disease-free survival (bDFS) rates in patients with low-, intermediate-and high risk groups were 100%, 86%, and 14%, respectively. All nine patients who received a post HIFU prostate biopsy showed no malignancy. Side-effects included urethral stricture in 4 of the 25 patients (16%) and urinary incontinence in 4 of the 25 patients (16%). Recto-urethral fistula occurred in one patient (4%). Salvage HIFU is a minimally invasive for patients with low-and intermediate risk group with comparable morbidity to other forms of salvage treatment.

Relationship between lower urinary tract symptoms and cardiovascular risk scores including Framingham risk score and ACC/AHA risk score.

PubMed

Lee, Bora; Lee, Sang Wook; Kang, Hye Rim; Kim, Dae In; Sun, Hwa Yeon; Kim, Jae Heon

2018-01-01

This study attempted to investigate the association between lower urinary tract symptoms (LUTS) and cardiovascular disease (CVD) risk using International Prostate Symptom Score (IPSS) and CVD risk scores and to overcome the limitations of previous relevant studies. A total of 2994 ostensibly healthy males, who participated in a voluntary health check in a health promotion center from January 2010 to December 2014, were reviewed. CVD risk scores were calculated using Framingham risk score and American College of Cardiology (ACC)/American Heart Association (AHA) score. Correlation and multivariate logistic regression analysis to predict the CVD risk severity were performed. Correlation between total IPSS with CVD risk scores demonstrated significant positive associations, which showed higher correlation with ACC/AHA score than the Framingham score (r = 0.18 vs 0.09, respectively). For ACC/AHA score, the partial correlation after adjustment of body mass index (BMI) showed significant positive correlations between all LUTS parameters and PSA. For the Framingham score, all variables, except IPSS Q2 and IPSS Q6, showed significant positive correlations. After adjustment of BMI, prostate volume and PSA, only the severe LUTS group showed significant relationship with intermediate-high CVD risk severity, as compared with normal LUTS group (OR = 2.97, 95%CI (1.35-6.99)). Using two validated CVD risk calculators, we observed that LUTS is closely associated with future CVD risk. To predict the intermediate-high CVD risk severity, severe LUTS was a sentinel sign, the presence of which warrants the importance of an earlier screening for CVD. © 2017 Wiley Periodicals, Inc.

New treatments for localized prostate cancer.

PubMed

Marberger, Michael; Carroll, Peter R; Zelefsky, Michael J; Coleman, Jonathan A; Hricak, Hedvig; Scardino, Peter T; Abenhaim, Lucien L

2008-12-01

Interest in focal therapy for prostate cancer has recently been renewed owing to downward stage migration, improved biopsy and imaging techniques, and the prevalence of either unifocal cancer or a dominant cancer with secondary tumors of minimal malignant potential. Several techniques have potential for focal ablation of prostate cancer. Cryotherapy has been used for some time as primary therapy for complete ablation of the prostate or local recurrence after radiotherapy. Enthusiasm for cryotherapy as the primary therapy has been tempered by the uncertainty about complete ablation of the cancer, the frequent persistence of measurable prostate-specific antigen levels after the procedure, and a high rate of erectile dysfunction. Studies have reported "focal ablation" of prostate cancer with cryotherapy, targeting 1 side of the gland to eliminate a cancer confined to that side with less risk of urinary or sexual complications. Whether cryotherapy has sufficient power to eradicate focal cancer and can be targeted with sufficient accuracy to avoid damage to surrounding structures remains to be demonstrated in prospective clinical trials. High-intensity focused ultrasound (HIFU) has been used widely in Europe for complete ablation of the prostate, especially in elderly men who are unwilling or unable to undergo radical therapy. For low- or intermediate-risk cancer, the short- and intermediate-term oncologic results have been acceptable but need confirmation in prospective multicenter trials presently underway. Whole gland therapy with transrectal ultrasound guidance has been associated with a high risk of acute urinary symptoms, often requiring transurethral resection before or after HIFU. Adverse effects on erectile function seem likely after a therapy that depends on heat to eradicate the cancer, but erectile function after HIFU has not been adequately documented with patient-reported questionnaires. HIFU holds promise for focal ablation of prostate cancer. As with cryotherapy, focal HIFU should reduce the adverse sexual, urinary, and bowel effects of whole gland ablation. New techniques are being developed to allow HIFU treatment under real-time guidance using magnetic resonance imaging, which could improve the precision and reduce the adverse effects further. Another promising technique, currently in clinical trials, is vascular-targeted photodynamic therapy, which has been used for whole gland ablation of locally recurrent cancer after radiotherapy and, more recently, for focal ablation of previously untreated cancer. In combination with a new, systemically administered photodynamic agent, laser light is delivered through fibers introduced into the prostate under ultrasound guidance. This technique does not heat the prostate but destroys the endothelial cells and cancer by activating the photodynamic agent. Damage to surrounding structures appears to be limited and can be controlled by the duration and intensity of the light. We have reviewed the principles of focal therapy and these new therapeutic modalities.

Focal therapy as primary treatment for localized prostate cancer: definition, needs and future.

PubMed

Ouzzane, Adil; Betrouni, Nacim; Valerio, Massimo; Rastinehad, Ardeshir; Colin, Pierre; Ploussard, Guillaume

2017-04-01

Focal therapy (FT) may offer a promising treatment option in the field of low to intermediate risk localized prostate cancer. The aim of this concept is to combine minimal morbidity with cancer control as well as maintain the possibility of retreatment. Recent advances in MRI and targeted biopsy has improved the diagnostic pathway of prostate cancer and increased the interest in FT. However, before implementation of FT in routine clinical practice, several challenges are still to overcome including patient selection, treatment planning, post-therapy monitoring and definition of oncologic outcome surrogates. In this article, relevant questions regarding the key steps of FT are critically discussed and the main available energy modalities are analyzed taking into account their advantages and unmet needs.

Beyond D'Amico risk classes for predicting recurrence after external beam radiotherapy for prostate cancer: the Candiolo classifier.

PubMed

Gabriele, Domenico; Jereczek-Fossa, Barbara A; Krengli, Marco; Garibaldi, Elisabetta; Tessa, Maria; Moro, Gregorio; Girelli, Giuseppe; Gabriele, Pietro

2016-02-24

The aim of this work is to develop an algorithm to predict recurrence in prostate cancer patients treated with radical radiotherapy, getting up to a prognostic power higher than traditional D'Amico risk classification. Two thousand four hundred ninety-three men belonging to the EUREKA-2 retrospective multi-centric database on prostate cancer and treated with external-beam radiotherapy as primary treatment comprised the study population. A Cox regression time to PSA failure analysis was performed in univariate and multivariate settings, evaluating the predictive ability of age, pre-treatment PSA, clinical-radiological staging, Gleason score and percentage of positive cores at biopsy (%PC). The accuracy of this model was checked with bootstrapping statistics. Subgroups for all the variables' combinations were combined to classify patients into five different "Candiolo" risk-classes for biochemical Progression Free Survival (bPFS); thereafter, they were also applied to clinical PFS (cPFS), systemic PFS (sPFS) and Prostate Cancer Specific Survival (PCSS), and compared to D'Amico risk grouping performances. The Candiolo classifier splits patients in 5 risk-groups with the following 10-years bPFS, cPFS, sPFS and PCSS: for very-low-risk 90 %, 94 %, 100 % and 100 %; for low-risk 74 %, 88 %, 94 % and 98 %; for intermediate-risk 60 %, 82 %, 91 % and 92 %; for high-risk 43 %, 55 %, 80 % and 89 % and for very-high-risk 14 %, 38 %, 56 % and 70 %. Our classifier outperforms D'Amico risk classes for all the end-points evaluated, with concordance indexes of 71.5 %, 75.5 %, 80 % and 80.5 % versus 63 %, 65.5 %, 69.5 % and 69 %, respectively. Our classification tool, combining five clinical and easily available parameters, seems to better stratify patients in predicting prostate cancer recurrence after radiotherapy compared to the traditional D'Amico risk classes.

Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study.

PubMed

Bancroft, Elizabeth K; Page, Elizabeth C; Castro, Elena; Lilja, Hans; Vickers, Andrew; Sjoberg, Daniel; Assel, Melissa; Foster, Christopher S; Mitchell, Gillian; Drew, Kate; Mæhle, Lovise; Axcrona, Karol; Evans, D Gareth; Bulman, Barbara; Eccles, Diana; McBride, Donna; van Asperen, Christi; Vasen, Hans; Kiemeney, Lambertus A; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Selkirk, Christina; Hulick, Peter J; Bojesen, Anders; Skytte, Anne-Bine; Lam, Jimmy; Taylor, Louise; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A; Oosterwijk, Jan C; Blanco, Ignacio; Salinas, Monica; Cook, Jackie; Rosario, Derek J; Buys, Saundra; Conner, Tom; Ausems, Margreet G; Ong, Kai-ren; Hoffman, Jonathan; Domchek, Susan; Powers, Jacquelyn; Teixeira, Manuel R; Maia, Sofia; Foulkes, William D; Taherian, Nassim; Ruijs, Marielle; Helderman-van den Enden, Apollonia T; Izatt, Louise; Davidson, Rosemarie; Adank, Muriel A; Walker, Lisa; Schmutzler, Rita; Tucker, Kathy; Kirk, Judy; Hodgson, Shirley; Harris, Marion; Douglas, Fiona; Lindeman, Geoffrey J; Zgajnar, Janez; Tischkowitz, Marc; Clowes, Virginia E; Susman, Rachel; Ramón y Cajal, Teresa; Patcher, Nicholas; Gadea, Neus; Spigelman, Allan; van Os, Theo; Liljegren, Annelie; Side, Lucy; Brewer, Carole; Brady, Angela F; Donaldson, Alan; Stefansdottir, Vigdis; Friedman, Eitan; Chen-Shtoyerman, Rakefet; Amor, David J; Copakova, Lucia; Barwell, Julian; Giri, Veda N; Murthy, Vedang; Nicolai, Nicola; Teo, Soo-Hwang; Greenhalgh, Lynn; Strom, Sara; Henderson, Alex; McGrath, John; Gallagher, David; Aaronson, Neil; Ardern-Jones, Audrey; Bangma, Chris; Dearnaley, David; Costello, Philandra; Eyfjord, Jorunn; Rothwell, Jeanette; Falconer, Alison; Gronberg, Henrik; Hamdy, Freddie C; Johannsson, Oskar; Khoo, Vincent; Kote-Jarai, Zsofia; Lubinski, Jan; Axcrona, Ulrika; Melia, Jane; McKinley, Joanne; Mitra, Anita V; Moynihan, Clare; Rennert, Gad; Suri, Mohnish; Wilson, Penny; Killick, Emma; Moss, Sue; Eeles, Rosalind A

2014-09-01

Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. To report the first year's screening results for all men at enrollment in the study. We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrollment, and those men with PSA >3 ng/ml were offered prostate biopsy. PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%-double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups. The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease. In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment. Copyright © 2014 European Association of Urology. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pommier, Pascal, E-mail: Pascal.pommier@lyon.unicancer.fr; Chabaud, Sylvie; Lagrange, Jean-Leon

Purpose: To report the long-term results of the French Genitourinary Study Group (GETUG)-01 study in terms of event-free survival (EFS) and overall survival (OS) and assess the potential interaction between hormonotherapy and pelvic nodes irradiation. Patients and Methods: Between December 1998 and June 2004, 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma were randomly assigned to either pelvic nodes and prostate or prostate-only radiation therapy. Patients were stratified into 2 groups: “low risk” (T1-T2 and Gleason score 6 and prostate-specific antigen <3× the upper normal limit of the laboratory) (92 patients) versus “high risk” (T3 or Gleason score >6 ormore » prostate-specific antigen >3× the upper normal limit of the laboratory). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for high-risk patients. Radiation therapy was delivered with a 3-dimensional conformal technique, using a 4-field technique for the pelvic volume (46 Gy). The total dose recommended to the prostate moved from 66 Gy to 70 Gy during the course of the study. Criteria for EFS included biologic prostate-specific antigen recurrences and/or a local or metastatic progression. Results: With a median follow-up of 11.4 years, the 10-year OS and EFS were similar in the 2 treatment arms. A higher but nonsignificant EFS was observed in the low-risk subgroup in favor of pelvic nodes radiation therapy (77.2% vs 62.5%; P=.18). A post hoc subgroup analysis showed a significant benefit of pelvic irradiation when the risk of lymph node involvement was <15% (Roach formula). This benefit seemed to be limited to patients who did not receive hormonal therapy. Conclusion: Pelvic nodes irradiation did not statistically improve EFS or OS in the whole population but may be beneficial in selected low- and intermediate-risk prostate cancer patients treated with exclusive radiation therapy.« less

Interrelationships among angiogenesis, proliferation, and apoptosis in the tumor microenvironment during N-methyl-N-nitrosourea androgen-induced prostate carcinogenesis in rats.

PubMed

Liao, Zhiming; Boileau, Thomas W-M; Erdman, John W; Clinton, Steven K

2002-10-01

Proliferation, apoptosis and angiogenesis are critical biologic processes altered during carcinogenesis. Surrogate biomarkers of these processes represent potential intermediate endpoints for short-term intervention studies with preventive and therapeutic agents. We examined the interrelationships among these processes during prostate carcinogenesis induced by N-methyl-N-nitrosourea (MNU) in male Wistar-Unilever rats. Immunohistochemical and digital image analysis techniques were used to evaluate the proliferation index, the apoptotic index and microvessel density (MVD) in tissue representing stages of prostate carcinogenesis. The proliferation index in the normal glandular epithelium of the prostate is lower than that observed in hyperplastic foci and atypical hyperplasia (P < 0.01) and is further increased in carcinoma (P < 0.01). Apoptosis in the normal prostate epithelium or hyperplastic lesions is lower than in adenocarcinoma (P < 0.01). In parallel to proliferation index, MVD increases as prostate cancer progresses. As tumors enlarge, we observed a predictable change in biomarker expression within the tumor microenvironment. We examined prostate tumors vertical line 1 cm in diameter and biomarker expression was quantified within the peripheral (outer 1-2 mm), central (perinecrotic) and intermediate (remaining) areas of each tumor. The proliferation index is higher (P < 0.01) in the intermediate area than either in the peripheral area or central area. Similarly, the vascular density in the intermediate area is higher (P < 0.01) than either in the peripheral or central area. The apoptotic index is higher (P < 0.05) in the central perinecrotic core than that in either the intermediate or the peripheral area. In conclusion, we observe that angiogenesis, proliferation and apoptosis are linked biological processes predictably altered temporally and spatially during prostate carcinogenesis in the MNU model. These biomarker changes are similar to those reported in human prostate carcinogenesis and represent potential biomarkers for the assessment of dietary, chemopreventive and therapeutic agents.

Prolaris Cell Cycle Progression Test for Localized Prostate Cancer: A Health Technology Assessment

PubMed Central

Schaink, Alexis; Li, Chunmei; Wells, David; Holubowich, Corinne

2017-01-01

Background Prostate cancer is very common and many localized tumours are non-aggressive. Determining which cancers are aggressive is important for choosing the most appropriate treatment (e.g., surgery, radiation, active surveillance). Current clinical risk stratification is reliable in forecasting the prognosis of groups of men with similar clinical and pathologic characteristics, but there is residual uncertainty at the individual level. The Prolaris cell cycle progression (CCP) test, a genomic test that estimates how fast tumour cells are proliferating, could potentially be used to improve the accuracy of individual risk assessment. This health technology assessment sought to determine the clinical utility, economic impact, and patients' perceptions of the value of the CCP test in low- and intermediate-risk localized prostate cancer. Methods We conducted a systematic review of the clinical and economic evidence of the CCP test in low-and intermediate-risk, localized prostate cancer. Medical and health economic databases were searched from 2010 to June or July 2016. The critical appraisal of the clinical evidence included risk of bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We also analyzed the potential budget impact of adding the CCP test into current practice, from the perspective the Ontario Ministry of Health and Long-Term Care. Finally, we conducted qualitative interviews with men with prostate cancer, on the factors that influenced their treatment decision-making. Results For the review of clinical effectiveness, we screened 3,021 citations, and two before–after studies met our inclusion criteria. In one study, the results of the CCP test appeared to change the treatment plan (from initial to final plan) in 64.9% of cases overall (GRADE rating of the quality of evidence: Very low). In the other study, the CCP test changed the treatment received in nearly half of cases overall, compared with the initial plan (GRADE: Very low). No evidence was available on clinical outcomes of patients whose treatment was informed by CCP results. For the review of cost-effectiveness, 100 citations were identified and screened. No studies met the inclusion criteria. In our economic evaluation, we estimated that publicly funding the CCP test would result in a total net budget impact of $41.3 million in the first 5 years, mostly due to the cost of the CCP test. In our model, the relatively small cost savings ($7.3 million) due to treatment change (increased use of active surveillance and decreased use of interventional treatment) was not large enough to offset the high cost of the test. Patients viewed the test as potentially helpful but, due to the complexity of treatment decision-making, were unsure the test would ultimately change their treatment choices. Conclusions We found no evidence to demonstrate the impact of the Prolaris CCP test on patient-important clinical outcomes. The limited evidence available shows that the test appears to provide information that, when considered in addition to clinical risk stratification, may change the treatment plan or actual treatment for some low- and intermediate-risk prostate cancer patients. As a result, there is insufficient data to inform the cost-effectiveness of the CCP test. Publicly funding the CCP test would result in a large incremental cost to the provincial budget. PMID:28572867

Incidence of thromboembolism after transurethral resection of the prostate (TURP)--a study on TED stocking prophylaxis and literature review.

PubMed

Donat, R; Mancey-Jones, B

2002-01-01

To assess the incidence of clinically evident pulmonary emboli and deep vein thromboses in patients undergoing transurethral resection of the prostate (TURP) with the routine use of graduated elastic compression stockings (TED) in all patients and the addition of low-dose heparin in selected high-risk patients. A retrospective analysis of clinically evident thromboembolic complications within 4 weeks of operation in 883 patients operated in a single hospital during a 4-year period. Four patients (0.45%) developed pulmonary emboli (PE), of which two (0.23%) were fatal. There was one clinically evident deep vein thrombosis (DVT) in a high-risk patient (0.11%). None of the 14 high-risk patients receiving additional low-dose heparin required a blood transfusion. Clinical thromboembolic complications following TURP are rare. TURP patients have a low risk for DVT, but an intermediate risk for pulmonary emboli. Pulmonary emboli may occur without identifiable risk factors and despite TED stocking prophylaxis.

Survival Following Radiation and Androgen Suppression Therapy for Prostate Cancer in Healthy Older Men: Implications for Screening Recommendations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Paul L., E-mail: pnguyen@LROC.harvard.ed; Department of Radiation Oncology, Dana Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA; Chen, Ming-Hui

2010-02-01

Purpose: The U.S. Preventive Services Task Force has recommended against screening men over 75 for prostate cancer. We examined whether older healthy men could benefit from aggressive prostate cancer treatment. Methods and Materials: 206 men with intermediate to high risk localized prostate cancer randomized to 70 Gy of radiation (RT) or RT plus 6 months of androgen suppression therapy (RT+AST) constituted the study cohort. Within subgroups stratified by Adult Comorbidity Evaluation-27 comorbidity score and age, Cox multivariable analysis was used to determine whether treatment with RT+AST as compared with RT was associated with a decreased risk of death. Results: Amongmore » healthy men (i.e., with mild or no comorbidity), 78 were older than the median age of 72.4 years, and in this subgroup, RT+AST was associated with a significantly lower risk of death on multivariable analysis (adjusted hazard ratio = 0.36 (95% CI=0.13-0.98), p = 0.046, with significantly lower 8-year mortality estimates of 16.5% vs. 41.4% (p = 0.011). Conversely, among men with moderate or severe comorbidity, 24 were older than the median age of 73, and in this subgroup, treatment with RT+AST was associated with a higher risk of death (adjusted hazard ratio = 5.2 (1.3-20.2), p = 0.018). Conclusion: In older men with mild or no comorbidity, treatment with RT+AST was associated with improved survival compared with treatment with RT alone, suggesting that healthy older men may derive the same benefits from prostate cancer treatment as younger men. We therefore suggest that prostate cancer screening recommendations should not be based on strict age cutoffs alone but should also take into account comorbidity.« less

A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling.

PubMed

Klein, Eric A; Cooperberg, Matthew R; Magi-Galluzzi, Cristina; Simko, Jeffry P; Falzarano, Sara M; Maddala, Tara; Chan, June M; Li, Jianbo; Cowan, Janet E; Tsiatis, Athanasios C; Cherbavaz, Diana B; Pelham, Robert J; Tenggara-Hunter, Imelda; Baehner, Frederick L; Knezevic, Dejan; Febbo, Phillip G; Shak, Steven; Kattan, Michael W; Lee, Mark; Carroll, Peter R

2014-09-01

Prostate tumor heterogeneity and biopsy undersampling pose challenges to accurate, individualized risk assessment for men with localized disease. To identify and validate a biopsy-based gene expression signature that predicts clinical recurrence, prostate cancer (PCa) death, and adverse pathology. Gene expression was quantified by reverse transcription-polymerase chain reaction for three studies-a discovery prostatectomy study (n=441), a biopsy study (n=167), and a prospectively designed, independent clinical validation study (n=395)-testing retrospectively collected needle biopsies from contemporary (1997-2011) patients with low to intermediate clinical risk who were candidates for active surveillance (AS). The main outcome measures defining aggressive PCa were clinical recurrence, PCa death, and adverse pathology at prostatectomy. Cox proportional hazards regression models were used to evaluate the association between gene expression and time to event end points. Results from the prostatectomy and biopsy studies were used to develop and lock a multigene-expression-based signature, called the Genomic Prostate Score (GPS); in the validation study, logistic regression was used to test the association between the GPS and pathologic stage and grade at prostatectomy. Decision-curve analysis and risk profiles were used together with clinical and pathologic characteristics to evaluate clinical utility. Of the 732 candidate genes analyzed, 288 (39%) were found to predict clinical recurrence despite heterogeneity and multifocality, and 198 (27%) were predictive of aggressive disease after adjustment for prostate-specific antigen, Gleason score, and clinical stage. Further analysis identified 17 genes representing multiple biological pathways that were combined into the GPS algorithm. In the validation study, GPS predicted high-grade (odds ratio [OR] per 20 GPS units: 2.3; 95% confidence interval [CI], 1.5-3.7; p<0.001) and high-stage (OR per 20 GPS units: 1.9; 95% CI, 1.3-3.0; p=0.003) at surgical pathology. GPS predicted high-grade and/or high-stage disease after controlling for established clinical factors (p<0.005) such as an OR of 2.1 (95% CI, 1.4-3.2) when adjusting for Cancer of the Prostate Risk Assessment score. A limitation of the validation study was the inclusion of men with low-volume intermediate-risk PCa (Gleason score 3+4), for whom some providers would not consider AS. Genes representing multiple biological pathways discriminate PCa aggressiveness in biopsy tissue despite tumor heterogeneity, multifocality, and limited sampling at time of biopsy. The biopsy-based 17-gene GPS improves prediction of the presence or absence of adverse pathology and may help men with PCa make more informed decisions between AS and immediate treatment. Prostate cancer (PCa) is often present in multiple locations within the prostate and has variable characteristics. We identified genes with expression associated with aggressive PCa to develop a biopsy-based, multigene signature, the Genomic Prostate Score (GPS). GPS was validated for its ability to predict men who have high-grade or high-stage PCa at diagnosis and may help men diagnosed with PCa decide between active surveillance and immediate definitive treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Favorable toxicity and biochemical control using real-time inverse optimization technique for prostate brachytherapy.

PubMed

Raben, Adam; Rusthoven, Kyle E; Sarkar, Abrihup; Glick, Andrew; Benge, Bruce; Jacobs, Dayee; Raben, David

2009-01-01

Favorable dosimetric results have been reported using intraoperative inverse optimization (IO) for permanent prostate brachytherapy. The clinical implications of these improvements in dosimetry are unclear. We review toxicity and early biochemical outcomes for patients implanted using IO technique. Between 2001 and 2007, 165 patients received permanent prostate implants using real-time IO and had >/=3 months of followup. Dose constraints for inverse planning were: the prostate volume receiving 100% of the prescription dose [prostate V(100)] was >95%; the dose received by 90% of the gland [prostate D(90)] was within the 140-180 by dose range; the volume of urethra receiving 150% of the prescription dose [urethra V(150)] was <30%; and the volume of rectal wall receiving 110% of the prescription dose [rectal V(110)] was <1.0 cc. Toxicity was prospectively scored using the Radiation Therapy Oncology Group toxicity scale and the International Prostate Symptom Score questionnaire. Biochemical control was determined using the nadir + 2 ng/mL definition. Mean followup was 30 months (range, 6-63 months). Risk classification was low risk in 89% and intermediate risk in 11%. Iodine-125 sources were used for 161 implants and palladium-103 sources for four implants. The median number of seeds and total activity implanted were 61 and 999 MBq, respectively, for a median prostate volume of 33.6 cc. Late GU and GI morbidity was uncommon. Among patients with at least 24 months followup, 16% had persistent Grade 2-3 urinary morbidity. Grade 2 rectal bleeding occurred in 1 patient (0.6%). Biochemical failure has occurred in only 4 patients at last followup. IO technique for prostate brachytherapy is associated with low rates of late morbidity and excellent early biochemical control. Additionally, the number of seeds and total implanted activity required to achieve a high-quality implant are lower compared with historical controls.

Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer.

PubMed

Park, Sonya Youngju; Zacharias, Claudia; Harrison, Caitlyn; Fan, Richard E; Kunder, Christian; Hatami, Negin; Giesel, Frederik; Ghanouni, Pejman; Daniel, Bruce; Loening, Andreas M; Sonn, Geoffrey A; Iagaru, Andrei

2018-05-16

Purpose To report the results of dual-time-point gallium 68 ( 68 Ga) prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/magnetic resonance (MR) imaging prior to prostatectomy in patients with intermediate- or high-risk cancer. Materials and Methods Thirty-three men who underwent conventional imaging as clinically indicated and who were scheduled for radical prostatectomy with pelvic lymph node dissection were recruited for this study. A mean dose of 4.1 mCi ± 0.7 (151.7 MBq ± 25.9) of 68 Ga-PSMA-11 was administered. Whole-body images were acquired starting 41-61 minutes after injection by using a GE SIGNA PET/MR imaging unit, followed by an additional pelvic PET/MR imaging acquisition at 87-125 minutes after injection. PET/MR imaging findings were compared with findings at multiparametric MR imaging (including diffusion-weighted imaging, T2-weighted imaging, and dynamic contrast material-enhanced imaging) and were correlated with results of final whole-mount pathologic examination and pelvic nodal dissection to yield sensitivity and specificity. Dual-time-point metabolic parameters (eg, maximum standardized uptake value [SUV max ]) were compared by using a paired t test and were correlated with clinical and histopathologic variables including prostate-specific antigen level, Gleason score, and tumor volume. Results Prostate cancer was seen at 68 Ga-PSMA-11 PET in all 33 patients, whereas multiparametric MR imaging depicted Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions in 26 patients and PI-RADS 3 lesions in four patients. Focal uptake was seen in the pelvic lymph nodes in five patients. Pathologic examination confirmed prostate cancer in all patients, as well as nodal metastasis in three. All patients with normal pelvic nodes in PET/MR imaging had no metastases at pathologic examination. The accumulation of 68 Ga-PSMA-11 increased at later acquisition times, with higher mean SUV max (15.3 vs 12.3, P < .001). One additional prostate cancer was identified only at delayed imaging. Conclusion This study found that 68 Ga-PSMA-11 PET can be used to identify prostate cancer, while MR imaging provides detailed anatomic guidance. Hence, 68 Ga-PSMA-11 PET/MR imaging provides valuable diagnostic information and may inform the need for and extent of pelvic node dissection. © RSNA, 2018 Online supplemental material is available for this article.

[18F]fluoroethylcholine-PET/CT imaging for radiation treatment planning of recurrent and primary prostate cancer with dose escalation to PET/CT-positive lymph nodes.

PubMed

Würschmidt, Florian; Petersen, Cordula; Wahl, Andreas; Dahle, Jörg; Kretschmer, Matthias

2011-05-01

At present there is no consensus on irradiation treatment volumes for intermediate to high-risk primary cancers or recurrent disease. Conventional imaging modalities, such as CT, MRI and transrectal ultrasound, are considered suboptimal for treatment decisions. Choline-PET/CT might be considered as the imaging modality in radiooncology to select and delineate clinical target volumes extending the prostate gland or prostate fossa. In conjunction with intensity modulated radiotherapy (IMRT) and imaged guided radiotherapy (IGRT), it might offer the opportunity of dose escalation to selected sites while avoiding unnecessary irradiation of healthy tissues. Twenty-six patients with primary (n = 7) or recurrent (n = 19) prostate cancer received Choline-PET/CT planned 3D conformal or intensity modulated radiotherapy. The median age of the patients was 65 yrs (range 45 to 78 yrs). PET/CT-scans with F18-fluoroethylcholine (FEC) were performed on a combined PET/CT-scanner equipped for radiation therapy planning. The majority of patients had intermediate to high risk prostate cancer. All patients received 3D conformal or intensity modulated and imaged guided radiotherapy with megavoltage cone beam CT. The median dose to primary tumours was 75.6 Gy and to FEC-positive recurrent lymph nodal sites 66,6 Gy. The median follow-up time was 28.8 months. The mean SUV(max) in primary cancer was 5,97 in the prostate gland and 3,2 in pelvic lymph nodes. Patients with recurrent cancer had a mean SUV(max) of 4,38. Two patients had negative PET/CT scans. At 28 months the overall survival rate is 94%. Biochemical relapse free survival is 83% for primary cancer and 49% for recurrent tumours. Distant disease free survival is 100% and 75% for primary and recurrent cancer, respectively. Acute normal tissue toxicity was mild in 85% and moderate (grade 2) in 15%. No or mild late side effects were observed in the majority of patients (84%). One patient had a severe bladder shrinkage (grade 4) after a previous treatment with TUR of the prostate and seed implantation. FEC-PET/CT planning could be helpful in dose escalation to lymph nodal sites of prostate cancer.

SU-F-T-394: Impact of PTV Margins With Taking Into Account Shape Variation On IMRT Plans For Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirose, T; Arimura, H; Oga, S

2016-06-15

Purpose: The purpose of this study was to investigate the impact of planning target volume (PTV) margins with taking into consideration clinical target volume (CTV) shape variations on treatment plans of intensity modulated radiation therapy (IMRT) for prostate cancer. Methods: The systematic errors and the random errors for patient setup errors in right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions were obtained from data of 20 patients, and those for CTV shape variations were calculated from 10 patients, who were weekly scanned using cone beam computed tomography (CBCT). The setup error was defined as the difference in prostate centers betweenmore » planning CT and CBCT images after bone-based registrations. CTV shape variations of high, intermediate and low risk CTVs were calculated for each patient from variances of interfractional shape variations on each vertex of three-dimensional CTV point distributions, which were manually obtained from CTV contours on the CBCT images. PTV margins were calculated using the setup errors with and without CTV shape variations for each risk CTV. Six treatment plans were retrospectively made by using the PTV margins with and without CTV shape variations for the three risk CTVs of 5 test patients. Furthermore, the treatment plans were applied to CBCT images for investigating the impact of shape variations on PTV margins. Results: The percentages of population to cover with the PTV, which satisfies the CTV D98 of 95%, with and without the shape variations were 89.7% and 74.4% for high risk, 89.7% and 76.9% for intermediate risk, 84.6% and 76.9% for low risk, respectively. Conclusion: PTV margins taking into account CTV shape variation provide significant improvement of applicable percentage of population (P < 0.05). This study suggested that CTV shape variation should be taken consideration into determination of the PTV margins.« less

Identification and Targeting of Candidate Preexisting Lurker Cells That Give Rise to Castration-Resistant Prostate Cancer

DTIC Science & Technology

2016-10-01

cells as the pre-existing “lurker” cells in primary prostate tumors, to evaluate potential therapeutic targets in intermediate luminal progenitor cells...intermediate luminal progenitor cells as the pre-existing “lurker” cells in primary prostate tumors, to evaluate potential therapeutic targets in...candidate target expressed in CD38-lo cells and evaluated the role of CD38 in cell proliferation. No prior Hormonal *** No prior therapy

Quality indicators for prostate radiotherapy: are patients disadvantaged by receiving treatment in a 'generalist' centre?

PubMed

Freeman, Amanda R; Roos, Daniel E; Kim, Laurence

2015-04-01

The purpose of this retrospective review was to evaluate concordance with evidence-based quality indicator guidelines for prostate cancer patients treated radically in a 'generalist' (as distinct from 'sub-specialist') centre. We were concerned that the quality of treatment may be lower in a generalist centre. If so, the findings could have relevance for many radiotherapy departments that treat prostate cancer. Two hundred fifteen consecutive patients received external beam radiotherapy (EBRT) and/or brachytherapy between 1.10.11 and 30.9.12. Treatment was deemed to be in line with evidence-based guidelines if the dose was: (i) 73.8-81 Gy at 1.8-2.0 Gy/fraction for EBRT alone (eviQ guidelines); (ii) 40-50 Gy (EBRT) for EBRT plus high-dose rate (HDR) brachytherapy boost (National Comprehensive Cancer Network (NCCN) guidelines); and (iii) 145 Gy for low dose rate (LDR) I-125 monotherapy (NCCN). Additionally, EBRT beam energy should be ≥6 MV using three-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT), and high-risk patients should receive neo-adjuvant androgen-deprivation therapy (ADT) (eviQ/NCCN). Treatment of pelvic nodes was also assessed. One hundred four high-risk, 84 intermediate-risk and 27 low-risk patients (NCCN criteria) were managed by eight of nine radiation oncologists. Concordance with guideline doses was confirmed in: (i) 125 of 136 patients (92%) treated with EBRT alone; (ii) 32 of 34 patients (94%) treated with EBRT + HDR BRT boost; and (iii) 45 of 45 patients (100%) treated with LDR BRT alone. All EBRT patients were treated with ≥6 MV beams using 3D-CRT (78%) or IMRT (22%). 84%, 21% and 0% of high-risk, intermediate-risk and low-risk patients received ADT, respectively. Overall treatment modality choice (including ADT use and duration where assessable) was concordant with guidelines for 176/207 (85%) of patients. The vast majority of patients were treated concordant with evidence-based guidelines suggesting that, within the limits of the selected criteria, prostate cancer patients are unlikely to be disadvantaged by receiving radiotherapy in this 'generalist' centre. © 2014 The Royal Australian and New Zealand College of Radiologists.

Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions

PubMed Central

Fellin, Giovanni; Mirri, Maria A; Santoro, Luigi; Divan, Claudio; Mussari, Salvatore; Ziglio, Francesco; La Face, Beniamino; Barbera, Fernando; Buglione, Michela; Bandera, Laura; Ghedi, Barbara; Di Muzio, Nadia G; Losa, Andrea; Mangili, Paola; Nava, Luciano; Chiarlone, Renato; Ciscognetti, Nunzia; Gastaldi, Emilio; Cattani, Federica; Spoto, Ruggero; Vavassori, Andrea; Giglioli, Francesca R; Guarneri, Alessia; Cerboneschi, Valentina; Mignogna, Marcello; Paoluzzi, Mauro; Ravaglia, Valentina; Chiumento, Costanza; Clemente, Stefania; Fusco, Vincenzo; Santini, Roberto; Stefanacci, Marco; Mangiacotti, Francesco P; Martini, Marco; Palloni, Tiziana; Schinaia, Giuseppe; Lazzari, Grazia; Silvano, Giovanni; Magrini, Stefano; Ricardi, Umberto; Santoni, Riccardo; Orecchia, Roberto

2016-01-01

Objective: Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. Methods: Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 (125I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. 125I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan–Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. Results: Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT. Conclusion: This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. Advances in knowledge: Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome. PMID:27384381

Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions.

PubMed

Fellin, Giovanni; Mirri, Maria A; Santoro, Luigi; Jereczek-Fossa, Barbara A; Divan, Claudio; Mussari, Salvatore; Ziglio, Francesco; La Face, Beniamino; Barbera, Fernando; Buglione, Michela; Bandera, Laura; Ghedi, Barbara; Di Muzio, Nadia G; Losa, Andrea; Mangili, Paola; Nava, Luciano; Chiarlone, Renato; Ciscognetti, Nunzia; Gastaldi, Emilio; Cattani, Federica; Spoto, Ruggero; Vavassori, Andrea; Giglioli, Francesca R; Guarneri, Alessia; Cerboneschi, Valentina; Mignogna, Marcello; Paoluzzi, Mauro; Ravaglia, Valentina; Chiumento, Costanza; Clemente, Stefania; Fusco, Vincenzo; Santini, Roberto; Stefanacci, Marco; Mangiacotti, Francesco P; Martini, Marco; Palloni, Tiziana; Schinaia, Giuseppe; Lazzari, Grazia; Silvano, Giovanni; Magrini, Stefano; Ricardi, Umberto; Santoni, Riccardo; Orecchia, Roberto

2016-09-01

Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT. This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome.

Prostate cancer survivors with a passive role preference in treatment decision-making are less satisfied with information received: Results from the PROFILES registry.

PubMed

Cuypers, Maarten; Lamers, Romy E D; de Vries, Marieke; Husson, Olga; Kil, Paul J M; van de Poll-Franse, Lonneke V

2016-11-01

To investigate decision-making role preferences and their association with the evaluation of information received in a sample of low-risk and intermediate-risk prostate cancer (Pca) survivors. Cross-sectional study involved 562 men diagnosed with low-risk or intermediate-risk Pca (median time since diagnosis, 48mo), measuring preferred decision-making role (Control Preference Scale) and the evaluation of information received (EORTC QLQ-INFO25). Analyses were performed using analysis of variance, chi-square tests, and multivariable linear regression models. Men who preferred a passive role were older and less educated than other preference groups and more often selected a noninvasive treatment option (all with P<0.001). The passive role preference group reported having received less information, judged the received information as less helpful, and indicated lower overall satisfaction with information received (all with P<0.05). Role preference groups did not differ in their desire to receive more information. Compared with nonpassive preference groups, the preference for a passive role in Pca treatment decision-making is associated with less satisfaction with the information received. Assessment of role preferences and tailored information provision could improve satisfaction with information received and perhaps may ultimately lead to improved patient participation in treatment decision-making. Copyright © 2016 Elsevier Inc. All rights reserved.

Technology Insight: Combined external-beam radiation therapy and brachytherapy in the management of prostate cancer.

PubMed

Hurwitz, Mark D

2008-11-01

External-beam radiation therapy (EBRT) combined with brachytherapy is an attractive treatment option for selected patients with clinically localized prostate cancer. This therapeutic strategy offers dosimetric coverage if local-regional microscopic disease is present and provides a highly conformal boost of radiation to the prostate and immediate surrounding tissues. Either low-dose-rate (LDR) permanent brachytherapy or high-dose-rate (HDR) temporary brachytherapy can be combined with EBRT; such combined-modality therapy (CMT) is typically used to treat patients with intermediate-risk to high-risk, clinically localized disease. Controversy persists with regard to indications for CMT, choice of LDR or HDR boost, isotope selection for LDR, and integration of EBRT and brachytherapy. Initial findings from prospective, multicenter trials of CMT support the feasibility of this strategy. Updated results from these trials as well as those of ongoing and new phase III trials should help to define the role of CMT in the management of prostate cancer. In the meantime, long-term expectations for outcomes of CMT are based largely on the experience of single institutions, which demonstrate that CMT with EBRT and either LDR or HDR brachytherapy can provide freedom from disease recurrence with acceptable toxicity.

Medium-term Outcomes after Whole-gland High-intensity Focused Ultrasound for the Treatment of Nonmetastatic Prostate Cancer from a Multicentre Registry Cohort.

PubMed

Dickinson, Louise; Arya, Manit; Afzal, Naveed; Cathcart, Paul; Charman, Susan C; Cornaby, Andrew; Hindley, Richard G; Lewi, Henry; McCartan, Neil; Moore, Caroline M; Nathan, Senthil; Ogden, Chris; Persad, Raj; van der Meulen, Jan; Weir, Shraddha; Emberton, Mark; Ahmed, Hashim U

2016-10-01

High-intensity focused ultrasound (HIFU) is a minimally-invasive treatment for nonmetastatic prostate cancer. To report medium-term outcomes in men receiving primary whole-gland HIFU from a national multi-centre registry cohort. Five-hundred and sixty-nine patients at eight hospitals were entered into an academic registry. Whole-gland HIFU (Sonablate 500) for primary nonmetastatic prostate cancer. Redo-HIFU was permitted as part of the intervention. Our primary failure-free survival outcome incorporated no transition to any of the following: (1) local salvage therapy (surgery or radiotherapy), (2) systemic therapy, (3) metastases, or (4) prostate cancer-specific mortality. Secondary outcomes included adverse events and genitourinary function. Mean age was 65 yr (47-87 yr). Median prostate-specific antigen was 7.0 ng/ml (interquartile range 4.4-10.2). National Comprehensive Cancer Network low-, intermediate-, and high-risk disease was 161 (28%), 321 (56%), and 81 (14%), respectively. One hundred and sixty three of 569 (29%) required a total of 185 redo-HIFU procedures. Median follow-up was 46 (interquartile range 23-61) mo. Failure-free survival at 5 yr after first HIFU was 70% (95% confidence interval [CI]: 64-74). This was 87% (95% CI: 78-93), 63% (95% CI: 56-70), and 58% (95% CI: 32-77) for National Comprehensive Cancer Network low-, intermediate-, and high-risk groups, respectively. Fifty eight of 754 (7.7%) had one urinary tract infection, 22/574 (2.9%) a recurrent urinary tract infection, 22/754 (3%) epididymo-orchitis, 227/754 (30%) endoscopic interventions, 1/754 (0.13%) recto-urethral fistula, and 1/754 (0.13%) osteitis pubis. Of 206 known to be pad-free pre-HIFU, 183/206 (88%) remained pad free, and of 236 with good baseline erectile function, 91/236 (39%) maintained good function. The main limitation is lack of long-term data. Whole-gland HIFU is a repeatable day-case treatment that confers low rates of urinary incontinence. Disease control at a median of just under 5 yr of follow-up demonstrates its potential as a treatment for nonmetastatic prostate cancer. Endoscopic interventions and erectile dysfunction rates are similar to other whole-gland treatments. In this report we looked at the 5-yr outcomes following whole-gland high-intensity focused ultrasound treatment for prostate cancer and found that cancer control was acceptable with a low risk of urine leakage. However, risk of erectile dysfunction and further operations was similar to other whole-gland treatments like surgery and radiotherapy. Copyright © 2016. Published by Elsevier B.V.

Adjuvant leuprolide with or without docetaxel in patients with high-risk prostate cancer after radical prostatectomy (TAX-3501): important lessons for future trials.

PubMed

Schweizer, Michael T; Huang, Peng; Kattan, Michael W; Kibel, Adam S; de Wit, Ronald; Sternberg, Cora N; Epstein, Jonathan I; Eisenberger, Mario A

2013-10-15

The current trial evaluated 2 common therapies for patients with advanced prostate cancer, docetaxel and hormonal therapy (HT), in the surgical adjuvant setting. TAX-3501 was a randomized, phase 3, adjuvant study post-radical prostatectomy (RP) in high-risk patients with prostate cancer (n=228) comparing 18 months of HT with (CHT) without docetaxel chemotherapy either immediately (I) or deferred (D). High-risk disease was defined as a 5-year freedom-from-disease-progression rate of ≤ 60% as predicted by a post-RP nomogram. Progression-free survival (PFS), including prostate-specific antigen disease recurrence, was the primary endpoint. The authors also assessed the accuracy of the nomogram and analyzed testosterone recovery in 108 patients treated with HT who had at least 1 posttreatment testosterone value. Between December 2005 and September 2007, 228 patients were randomized between the treatment cohorts. TAX-3501 was terminated prematurely because of enrollment challenges, leaving it underpowered to detect differences in PFS. After a median follow-up of 3.4 years (interquartile range, 2.3-3.8 years), 39 of 228 patients (17%) demonstrated PSA disease progression, and metastatic disease progression occurred in 1 patient. The median time to baseline testosterone recovery after the completion of treatment was prolonged at 487 days (95% confidence interval, 457-546 days). The nomogram's predicted versus observed freedom from disease progression was significantly different for the combination D(HT) and D(CHT) group (P<.00001). TAX-3501 illustrated several difficulties involved in conducting postoperative adjuvant systemic trials in men with high-risk prostate cancer: the lack of consensus regarding patient selection and treatment, the need for long follow-up time, nonvalidated intermediate endpoints, evolving standard approaches, and the need for long-term research support. Except for selected patients at very high-risk of disease recurrence and death, surgical adjuvant trials in patients with prostate cancer may not be feasible. Copyright © 2013 American Cancer Society.

Outcomes of men with an elevated prostate-specific antigen (PSA) level as their sole preoperative intermediate- or high-risk feature.

PubMed

Faisal, Farzana A; Sundi, Debasish; Pierorazio, Phillip M; Ball, Mark W; Humphreys, Elizabeth B; Han, Misop; Epstein, Jonathan I; Partin, Alan W; Carter, H Ballentine; Bivalacqua, Trinity J; Schaeffer, Edward M; Ross, Ashley E

2014-12-01

To investigate the post-prostatectomy and long-term outcomes of men presenting with an elevated pretreatment prostate-specific antigen (PSA) level (>10 ng/mL), but otherwise low-risk features (biopsy Gleason score ≤6 and clinical stage ≤T2a). PSA-incongruent intermediate-risk (PII) cases were defined as those patients with preoperative PSA >10 and ≤20 ng/mL but otherwise low-risk features, and PSA-incongruent high-risk (PIH) cases were defined as men with PSA >20 ng/mL but otherwise low-risk features. Our institutional radical prostatectomy database (1992-2012) was queried and the results were stratified into D'Amico low-, intermediate- and high risk, PSA-incongruent intermediate-risk and PSA-incongruent high-risk cases. Prostate cancer (PCa) features and outcomes were evaluated using appropriate comparative tests. Multivariable analyses were adjusted for age, race and year of surgery. Of the total cohort of 17 608 men, 1132 (6.4%) had PII-risk disease and 183 (1.0%) had PIH-risk disease. Compared with the low-risk group, the odds of upgrading at radical prostatectomy (RP) were 2.20 (95% CI 1.93-2.52; P < 0.001) for the PII group and 3.58 (95% CI 2.64-4.85; P < 0.001) for the PIH group, the odds of extraprostatic disease at RP were 2.35 (95% CI 2.05-2.68; P < 0.001) for the PII group and 6.68 (95% CI 4.89-9.15; P < 0.001) for the PIH group, and the odds of positive surgical margins were 1.97 (95% CI 1.67-2.33; P < 0.001) for the PII group and 3.54 (95% CI 2.50-4.95, P < 0.001) for the PIH group. Compared with low-risk disease, PII-risk disease was associated with a 2.85-, 2.99- and 3.32-fold greater risk of biochemical recurrence (BCR), metastasis and PCa-specific mortality, respectively, and PIH-risk disease was associated with a 5.32-, 6.14- and 7.07-fold greater risk of BCR, metastasis and PCa-specific mortality, respectively (P ≤ 0.001 for all comparisons). For the PII group, the higher risks of positive surgical margins, upgrading, upstaging and BCR were dependent on PSA density (PSAD): men in the PII group who had a PSAD <0.15 ng/mL/g were not at higher risk compared with those in the low-risk group. Men in the PII group with a PSAD ≥0.15 ng/mL/g and men in the PIH group were more likely to have an anterior component of the dominant tumour (59 and 64%, respectively) compared with those in the low- (35%) and intermediate-risk group (39%) and those in the PII-risk group with PSAD <0.15 ng/mL/g (29%). Men with PSA >20 ng/mL or men with PSA >10 and ≤20 ng/mL with a PSAD ≥0.15 ng/mL/g, but otherwise low-risk PCa, are at greater risk of adverse pathological and oncological outcomes and may be inappropriate candidates for active surveillance. These men are at greater risk of having anterior tumours that are undersampled at biopsy, so if treatment is deferred, ancillary testing such as anterior zone sampling or magnetic resonance imaging should be strongly encouraged. Men with elevated PSA levels >10 and ≤20 ng/mL but low PSAD have outcomes similar to those in the low-risk group, and consideration of surveillance is appropriate in these cases. © 2014 The Authors. BJU International © 2014 BJU International.

A TCP model for external beam treatment of intermediate-risk prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walsh, Sean; Putten, Wil van der

2013-03-15

Purpose: Biological models offer the ability to predict clinical outcomes. The authors describe a model to predict the clinical response of intermediate-risk prostate cancer to external beam radiotherapy for a variety of fractionation regimes. Methods: A fully heterogeneous population averaged tumor control probability model was fit to clinical outcome data for hyper, standard, and hypofractionated treatments. The tumor control probability model was then employed to predict the clinical outcome of extreme hypofractionation regimes, as utilized in stereotactic body radiotherapy. Results: The tumor control probability model achieves an excellent level of fit, R{sup 2} value of 0.93 and a root meanmore » squared error of 1.31%, to the clinical outcome data for hyper, standard, and hypofractionated treatments using realistic values for biological input parameters. Residuals Less-Than-Or-Slanted-Equal-To 1.0% are produced by the tumor control probability model when compared to clinical outcome data for stereotactic body radiotherapy. Conclusions: The authors conclude that this tumor control probability model, used with the optimized radiosensitivity values obtained from the fit, is an appropriate mechanistic model for the analysis and evaluation of external beam RT plans with regard to tumor control for these clinical conditions.« less

Investigation of interfractional shape variations based on statistical point distribution model for prostate cancer radiation therapy.

PubMed

Shibayama, Yusuke; Arimura, Hidetaka; Hirose, Taka-Aki; Nakamoto, Takahiro; Sasaki, Tomonari; Ohga, Saiji; Matsushita, Norimasa; Umezu, Yoshiyuki; Nakamura, Yasuhiko; Honda, Hiroshi

2017-05-01

The setup errors and organ motion errors pertaining to clinical target volume (CTV) have been considered as two major causes of uncertainties in the determination of the CTV-to-planning target volume (PTV) margins for prostate cancer radiation treatment planning. We based our study on the assumption that interfractional target shape variations are not negligible as another source of uncertainty for the determination of precise CTV-to-PTV margins. Thus, we investigated the interfractional shape variations of CTVs based on a point distribution model (PDM) for prostate cancer radiation therapy. To quantitate the shape variations of CTVs, the PDM was applied for the contours of 4 types of CTV regions (low-risk, intermediate- risk, high-risk CTVs, and prostate plus entire seminal vesicles), which were delineated by considering prostate cancer risk groups on planning computed tomography (CT) and cone beam CT (CBCT) images of 73 fractions of 10 patients. The standard deviations (SDs) of the interfractional random errors for shape variations were obtained from covariance matrices based on the PDMs, which were generated from vertices of triangulated CTV surfaces. The correspondences between CTV surface vertices were determined based on a thin-plate spline robust point matching algorithm. The systematic error for shape variations was defined as the average deviation between surfaces of an average CTV and planning CTVs, and the random error as the average deviation of CTV surface vertices for fractions from an average CTV surface. The means of the SDs of the systematic errors for the four types of CTVs ranged from 1.0 to 2.0 mm along the anterior direction, 1.2 to 2.6 mm along the posterior direction, 1.0 to 2.5 mm along the superior direction, 0.9 to 1.9 mm along the inferior direction, 0.9 to 2.6 mm along the right direction, and 1.0 to 3.0 mm along the left direction. Concerning the random errors, the means of the SDs ranged from 0.9 to 1.2 mm along the anterior direction, 1.0 to 1.4 mm along the posterior direction, 0.9 to 1.3 mm along the superior direction, 0.8 to 1.0 mm along the inferior direction, 0.8 to 0.9 mm along the right direction, and 0.8 to 1.0 mm along the left direction. Since the shape variations were not negligible for intermediate and high-risk CTVs, they should be taken into account for the determination of the CTV-to-PTV margins in radiation treatment planning of prostate cancer. © 2017 American Association of Physicists in Medicine.

Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study

PubMed Central

Bancroft, Elizabeth K.; Page, Elizabeth C.; Castro, Elena; Lilja, Hans; Vickers, Andrew; Sjoberg, Daniel; Assel, Melissa; Foster, Christopher S.; Mitchell, Gillian; Drew, Kate; Mæhle, Lovise; Axcrona, Karol; Evans, D. Gareth; Bulman, Barbara; Eccles, Diana; McBride, Donna; van Asperen, Christi; Vasen, Hans; Kiemeney, Lambertus A.; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Selkirk, Christina; Hulick, Peter J.; Bojesen, Anders; Skytte, Anne-Bine; Lam, Jimmy; Taylor, Louise; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A.; Oosterwijk, Jan C.; Blanco, Ignacio; Salinas, Monica; Cook, Jackie; Rosario, Derek J.; Buys, Saundra; Conner, Tom; Ausems, Margreet G.; Ong, Kai-ren; Hoffman, Jonathan; Domchek, Susan; Powers, Jacquelyn; Teixeira, Manuel R.; Maia, Sofia; Foulkes, William D.; Taherian, Nassim; Ruijs, Marielle; den Enden, Apollonia T. Helderman-van; Izatt, Louise; Davidson, Rosemarie; Adank, Muriel A.; Walker, Lisa; Schmutzler, Rita; Tucker, Kathy; Kirk, Judy; Hodgson, Shirley; Harris, Marion; Douglas, Fiona; Lindeman, Geoffrey J.; Zgajnar, Janez; Tischkowitz, Marc; Clowes, Virginia E.; Susman, Rachel; Ramón y Cajal, Teresa; Patcher, Nicholas; Gadea, Neus; Spigelman, Allan; van Os, Theo; Liljegren, Annelie; Side, Lucy; Brewer, Carole; Brady, Angela F.; Donaldson, Alan; Stefansdottir, Vigdis; Friedman, Eitan; Chen-Shtoyerman, Rakefet; Amor, David J.; Copakova, Lucia; Barwell, Julian; Giri, Veda N.; Murthy, Vedang; Nicolai, Nicola; Teo, Soo-Hwang; Greenhalgh, Lynn; Strom, Sara; Henderson, Alex; McGrath, John; Gallagher, David; Aaronson, Neil; Ardern-Jones, Audrey; Bangma, Chris; Dearnaley, David; Costello, Philandra; Eyfjord, Jorunn; Rothwell, Jeanette; Falconer, Alison; Gronberg, Henrik; Hamdy, Freddie C.; Johannsson, Oskar; Khoo, Vincent; Kote-Jarai, Zsofia; Lubinski, Jan; Axcrona, Ulrika; Melia, Jane; McKinley, Joanne; Mitra, Anita V.; Moynihan, Clare; Rennert, Gad; Suri, Mohnish; Wilson, Penny; Killick, Emma; Moss, Sue; Eeles, Rosalind A.

2014-01-01

Background Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. Objective To report the first year's screening results for all men at enrolment in the study. Design, setting and participants We recruited men aged 40–69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrolment, and those men with PSA >3 ng/ml were offered prostate biopsy. Outcome measurements and statistical analysis PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. Results and limitations We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%—double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups. Conclusions The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease. Patient summary In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment. PMID:24484606

PSA nadir of <0.5 ng/mL following brachytherapy for early-stage prostate adenocarcinoma is associated with freedom from prostate-specific antigen failure.

PubMed

Ko, Eric C; Stone, Nelson N; Stock, Richard G

2012-06-01

Because limited information exists regarding whether the rate or magnitude of PSA decline following brachytherapy predicts long-term clinical outcomes, we evaluated whether achieving a prostate-specific antigen (PSA) nadir (nPSA) <0.5 ng/mL following brachytherapy is associated with decreased PSA failure and/or distant metastasis. We retrospectively analyzed our database of early-stage prostate adenocarcinoma patients who underwent brachytherapy, excluding those receiving androgen-deprivation therapy and those with <2 years follow-up. Median and mean pretreatment PSA were 6 ng/mL and 7.16 ng/mL, respectively. By clinical stage, 775 were low risk (≤ T2a), 126 were intermediate risk (T2b), and 20 were high risk (>T2b). By Gleason score, 840 were low risk (≤ 6), 71 were intermediate risk (7), and 10 were high risk (>7). Patients were treated with brachytherapy only (I-125, n = 779, or Pd-103, n = 47), or brachytherapy + external-beam radiation therapy (n = 95). Median follow-up was 6.3 years. We noted whether nPSA <0.5 ng/mL was achieved and the time to achieve this nadir and tested for associations with pretreatment risk factors. We also determined whether this PSA endpoint was associated with decreased PSA failure or distant metastasis. Absence of high-risk factors in clinical stage (≤ T2b), Gleason score (≤ 7), and pretreatment PSA (≤ 20 ng/mL) was significantly associated with achieving nPSA <0.5 ng/mL. By Kaplan-Meier analysis, patients achieving nPSA <0.5 ng/mL had significantly higher long-term freedom from biochemical failure (FFBF) than nonresponders (5-year FFBF: 95.2 ± 0.8% vs. 71.5 ± 6.7%; p < 0.0005). Among responders, those who achieved nPSA <0.5 ng/mL in ≤ 5 years had higher FFBF than those requiring >5 years (5-year FFBF: 96.7 ± 0.7% vs. 80.8 ± 4.6%; p < 0.0005). On multivariate analysis, patients who achieved nPSA <0.5 ng/mL in ≤ 5 years had significantly higher FFBF than other patients. Pretreatment risk factors (clinical tumor stage, Gleason score, pretreatment PSA) strongly predict for patients achieving nPSA <0.5 ng/mL following brachytherapy, and this cohort had significantly higher long-term FFBF. Copyright © 2012 Elsevier Inc. All rights reserved.

Percentage of Positive Biopsy Cores: A Better Risk Stratification Model for Prostate Cancer?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang Jiayi; Vicini, Frank A.; Williams, Scott G.

2012-07-15

Purpose: To assess the prognostic value of the percentage of positive biopsy cores (PPC) and perineural invasion in predicting the clinical outcomes after radiotherapy (RT) for prostate cancer and to explore the possibilities to improve on existing risk-stratification models. Methods and Materials: Between 1993 and 2004, 1,056 patients with clinical Stage T1c-T3N0M0 prostate cancer, who had four or more biopsy cores sampled and complete biopsy core data available, were treated with external beam RT, with or without a high-dose-rate brachytherapy boost at William Beaumont Hospital. The median follow-up was 7.6 years. Multivariate Cox regression analysis was performed with PPC, Gleasonmore » score, pretreatment prostate-specific antigen, T stage, PNI, radiation dose, androgen deprivation, age, prostate-specific antigen frequency, and follow-up duration. A new risk stratification (PPC classification) was empirically devised to incorporate PPC and replace the T stage. Results: On multivariate Cox regression analysis, the PPC was an independent predictor of distant metastasis, cause-specific survival, and overall survival (all p < .05). A PPC >50% was associated with significantly greater distant metastasis (hazard ratio, 4.01; 95% confidence interval, 1.86-8.61), and its independent predictive value remained significant with or without androgen deprivation therapy (all p < .05). In contrast, PNI and T stage were only predictive for locoregional recurrence. Combining the PPC ({<=}50% vs. >50%) with National Comprehensive Cancer Network risk stratification demonstrated added prognostic value of distant metastasis for the intermediate-risk (hazard ratio, 5.44; 95% confidence interval, 1.78-16.6) and high-risk (hazard ratio, 4.39; 95% confidence interval, 1.70-11.3) groups, regardless of the use of androgen deprivation and high-dose RT (all p < .05). The proposed PPC classification appears to provide improved stratification of the clinical outcomes relative to the National Comprehensive Cancer Network classification. Conclusions: The PPC is an independent and powerful predictor of clinical outcomes of prostate cancer after RT. A risk model replacing T stage with the PPC to reduce subjectivity demonstrated potentially improved stratification.« less

Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morris, W. James, E-mail: jmorris@bccancer.bc.ca; BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia; Tyldesley, Scott

Purpose: To report the primary endpoint of biochemical progression-free survival (b-PFS) and secondary survival endpoints from ASCENDE-RT, a randomized trial comparing 2 methods of dose escalation for intermediate- and high-risk prostate cancer. Methods and Materials: ASCENDE-RT enrolled 398 men, with a median age of 68 years; 69% (n=276) had high-risk disease. After stratification by risk group, the subjects were randomized to a standard arm with 12 months of androgen deprivation therapy, pelvic irradiation to 46 Gy, followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. Of the 398more » trial subjects, 200 were assigned to DE-EBRT boost and 198 to LDR-PB boost. The median follow-up was 6.5 years. Results: In an intent-to-treat analysis, men randomized to DE-EBRT were twice as likely to experience biochemical failure (multivariable analysis [MVA] hazard ratio [HR] 2.04; P=.004). The 5-, 7-, and 9-year Kaplan-Meier b-PFS estimates were 89%, 86%, and 83% for the LDR-PB boost versus 84%, 75%, and 62% for the DE-EBRT boost (log-rank P<.001). The LDR-PB boost benefited both intermediate- and high-risk patients. Because the b-PFS curves for the treatment arms diverge sharply after 4 years, the relative advantage of the LDR-PB should increase with longer follow-up. On MVA, the only variables correlated with reduced overall survival were age (MVA HR 1.06/y; P=.004) and biochemical failure (MVA HR 6.30; P<.001). Although biochemical failure was associated with increased mortality and randomization to DE-EBRT doubled the rate of biochemical failure, no significant overall survival difference was observed between the treatment arms (MVA HR 1.13; P=.62). Conclusions: Compared with 78 Gy EBRT, men randomized to the LDR-PB boost were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years.« less

SU-F-J-157: Effect of Contouring Uncertainty in Post Implant Dosimetry of Low-Dose-Rate Prostate Permanent Seed Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mashouf, S; Merino, T; Ravi, A

Purpose: There is strong evidence relating post-implant dosimetry for low-dose-rate (LDR) prostate seed brachytherapy to local control rates. The delineation of the prostate on CT images, however, represents a challenge due to the lack of soft tissue contrast in order to identify the prostate borders. This study aims at quantifying the sensitivity of clinically relevant dosimetric parameters to uncertainty in the contouring of prostate. Methods: CT images, post-op plans and contours of a cohort of patients (n=43) (low risk=55.8%, intermediate risk=39.5%, high risk=4.7%), who had received prostate seed brachytherapy, were imported into MIM Symphony treatment planning system. The prostate contoursmore » in post-implant CT images were expanded/contracted uniformly for margins of ±1.00 mm, ±2.00 mm, ±3.00 mm, ±4.00 mm and ±5.00 mm. The values for V100 and D90 were extracted from Dose Volume Histograms for each contour and compared. Results: Significant changes were observed in the values of D90 and V100 as well as the number of suboptimal plans for expansion or contraction margins of only few millimeters. Evaluation of coverage based on D90 was found to be less sensitive to expansion errors compared to V100. D90 led to a lower number of implants incorrectly identified with insufficient coverage for expanded contours which increases the accuracy of post-implant QA using CT images compared to V100. Conclusion: In order to establish a successful post implant QA for LDR prostate seed brachytherapy, it is necessary to identify the low and high thresholds of important dose metrics of the target volume such as D90 and V100. Since these parameters are sensitive to target volume definition, accurate identification of prostate borders would help to improve accuracy and predictive value of the post-implant QA process. In this respect, use of imaging modalities such as MRI where prostate is well delineated should prove useful.« less

Posttreatment Prostate-Specific Antigen 6 Months After Radiation With Androgen Deprivation Therapy Predicts for Distant Metastasis–Free Survival and Prostate Cancer–Specific Mortality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naik, Mihir, E-mail: naikm@ccf.org; Reddy, Chandana A.; Stephans, Kevin L.

Objectives/Background: To determine whether a 6-month posttreatment prostate-specific antigen (PSA) value in patients with prostate cancer (PCa) treated with concurrent androgen deprivation therapy (ADT) and external beam radiation therapy (EBRT) serves as an early predictor for biochemical relapse free survival (bRFS), distant metastasis–free survival (DMFS), and prostate cancer–specific mortality (PCSM). Methods: A retrospective review of intermediate-risk and high-risk PCa patients treated with EBRT and concurrent ADT at a single institution between 1996 and 2012. All patients received high-dose radiation with either 78 Gy in 39 fractions or 70 Gy in 28 fractions. Kaplan-Meier analysis was used to estimate bRFS and DMFS, andmore » cumulative incidence was used to estimate PCSM. Results: 532 patients were identified. The median follow-up time was 7.5 years (range, 1-16.25 years). The median initial PSA (iPSA) was 13.0 ng/mL (range, 0.37-255 ng/mL), and the median duration of ADT was 6 months (range, 1-78 months). The median PSA 6 months after EBRT was 0.1 ng/mL (range, 0-19 ng/mL), and 310 patients (58.3%) had a 6-month PSA ≤0.1 ng/mL. Multivariable analysis (MVA) demonstrated that a 6-month post-EBRT PSA of >0.1 ng/mL was an independent predictor of worse bRFS (hazard ratio [HR] = 2.518; P<.0001), DMFS (HR=3.743; P<.0001), and PCSM (HR=5.435; P<.0001). On MVA, a Gleason score of 8 to 10 also correlated with worse DMFS and PCSM (P<.05). The duration of ADT (1-6 vs >6 months) was not predictive of any clinical endpoint. Conclusions: A 6-month posttreatment PSA >0.1 ng/mL in intermediate-risk and high-risk PCa patients treated with concurrent high-dose EBRT and ADT is associated with worse bRFS, DMFS, and PCSM. The duration of ADT was not predictive of any clinical endpoint. A 6-month PSA after definitive EBRT and ADT helps identify patients at higher risk of disease progression and may serve as a predictive tool to select patients for early salvage therapy on future clinical trials.« less

Is choline PET useful for identifying intraprostatic tumour lesions? A literature review.

PubMed

Chan, Joachim; Syndikus, Isabel; Mahmood, Shelan; Bell, Lynn; Vinjamuri, Sobhan

2015-09-01

More than 80% of patients with intermediate-risk or high-risk localized prostate cancer are cured with radiation doses of 74-78 Gy, but high doses increase the risk for late bowel and bladder toxicity among long-term survivors. Dose painting, defined as dose escalation to areas in the prostate containing the tumour, rather than to the whole gland, minimizes dose to normal tissues and hence toxicity. It requires accurate identification of the location and size of these lesions, for which functional MRI is the current gold standard. Many studies have assessed the use of choline PET in staging newly diagnosed patients. This review will discuss important imaging variables affecting the accuracy of choline PET scans, how choline PET contributes to tumour identification and is used in radiotherapy planning and how PET can improve the patient pathway involving prostate radiotherapy. In summary, the available literature shows that the accuracy of choline PET improves with higher tracer doses and delayed imaging (although the optimal uptake time is unclear), and tumour identification by MRI is improved by the addition of PET imaging. We propose future research with prolonged choline uptake time and multiphase imaging, which may further improve accuracy.

Duration of Androgen Suppression Before Radiotherapy for Localized Prostate Cancer: Radiation Therapy Oncology Group Randomized Clinical Trial 9910

PubMed Central

Pisansky, Thomas M.; Hunt, Daniel; Gomella, Leonard G.; Amin, Mahul B.; Balogh, Alexander G.; Chinn, Daniel M.; Seider, Michael J.; Duclos, Marie; Rosenthal, Seth A.; Bauman, Glenn S.; Gore, Elizabeth M.; Rotman, Marvin Z.; Lukka, Himanshu R.; Shipley, William U.; Dignam, James J.; Sandler, Howard M.

2015-01-01

Purpose To determine whether prolonged androgen suppression (AS) duration before radiotherapy improves survival and disease control in prostate cancer. Patients and Methods One thousand five hundred seventy-nine men with intermediate-risk prostate cancer were randomly assigned to 8 weeks of AS followed by radiotherapy with an additional 8 weeks of concurrent AS (16 weeks total) or to 28 weeks of AS followed by radiotherapy with an additional 8 weeks of AS (36 weeks total). The trial sought primarily to detect a 33% reduction in the hazard of prostate cancer death in the 28-week assignment. Time-to-event end points are reported for up to 10 years of follow-up. Results There were no between-group differences in baseline characteristics of 1,489 eligible patients with follow-up. For the 8- and 28-week assignments, 10-year disease-specific survival rates were 95% (95% CI, 93.3% to 97.0%) and 96% (95% CI, 94.6% to 98.0%; hazard ratio [HR], 0.81; P = .45), respectively, and 10-year overall survival rates were 66% (95% CI, 62.0% to 69.9%) and 67% (95% CI, 63.0% to 70.8%; HR, 0.95; P = .62), respectively. For the 8- and 28-week assignments, 10-year cumulative incidences of locoregional progression were 6% (95% CI, 4.3% to 8.0%) and 4% (95% CI, 2.5% to 5.7%; HR, 0.65; P = .07), respectively; 10-year distant metastasis cumulative incidences were 6% (95% CI, 4.0% to 7.7%) and 6% (95% CI, 4.0% to 7.6%; HR, 1.07; P = .80), respectively; and 10-year prostate-specific antigen–based recurrence cumulative incidences were 27% (95% CI, 23.1% to 29.8%) and 27% (95% CI, 23.4% to 30.3%; HR, 0.97; P = .77), respectively. Conclusion Extending AS duration from 8 weeks to 28 weeks before radiotherapy did not improve outcomes. A lower than expected prostate cancer death rate reduced ability to detect a between-group difference in disease-specific survival. The schedule of 8 weeks of AS before radiotherapy plus 8 weeks of AS during radiotherapy remains a standard of care in intermediate-risk prostate cancer. PMID:25534388

Prostate Cancer Patient Characteristics Associated With a Strong Preference to Preserve Sexual Function and Receipt of Active Surveillance.

PubMed

Broughman, James R; Basak, Ramsankar; Nielsen, Matthew E; Reeve, Bryce B; Usinger, Deborah S; Spearman, Kiayni C; Godley, Paul A; Chen, Ronald C

2018-04-01

Men with early-stage prostate cancer have multiple options that have similar oncologic efficacy but vary in terms of their impact on quality of life. In low-risk cancer, active surveillance is the option that best preserves patients' sexual function, but it is unknown if patient preference affects treatment selection. Our objectives were to identify patient characteristics associated with a strong preference to preserve sexual function and to determine whether patient preference and baseline sexual function level are associated with receipt of active surveillance in low-risk cancer. In this population-based cohort of men with localized prostate cancer, baseline patient-reported sexual function was assessed using a validated instrument. Patients were also asked whether preservation of sexual function was very, somewhat, or not important. Prostate cancer disease characteristics and treatments received were abstracted from medical records. A modified Poisson regression model with robust standard errors was used to compute adjusted risk ratio (aRR) estimates. All statistical tests were two-sided. Among 1194 men, 52.6% indicated a strong preference for preserving sexual function. Older men were less likely to have a strong preference (aRR = 0.98 per year, 95% confidence interval [CI] = 0.97 to 0.99), while men with normal sexual function were more likely (vs poor function, aRR = 1.59, 95% CI = 1.39 to 1.82). Among 568 men with low-risk cancer, there was no clear association between baseline sexual function or strong preference to preserve function with receipt of active surveillance. However, strong preference may differnetially impact those with intermediate baseline function vs poor function (Pinteraction = .02). Treatment choice may not always align with patients' preferences. These findings demonstrate opportunities to improve delivery of patient-centered care in early prostate cancer.

PSA Nadir of <0.5 ng/mL Following Brachytherapy for Early-Stage Prostate Adenocarcinoma is Associated With Freedom From Prostate-Specific Antigen Failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ko, Eric C.; Stone, Nelson N.; Department of Urology, Mount Sinai Medical Center, New York, NY

2012-06-01

Purpose: Because limited information exists regarding whether the rate or magnitude of PSA decline following brachytherapy predicts long-term clinical outcomes, we evaluated whether achieving a prostate-specific antigen (PSA) nadir (nPSA) <0.5 ng/mL following brachytherapy is associated with decreased PSA failure and/or distant metastasis. Methods and Materials: We retrospectively analyzed our database of early-stage prostate adenocarcinoma patients who underwent brachytherapy, excluding those receiving androgen-deprivation therapy and those with <2 years follow-up. Median and mean pretreatment PSA were 6 ng/mL and 7.16 ng/mL, respectively. By clinical stage, 775 were low risk ({<=}T2a), 126 were intermediate risk (T2b), and 20 were high riskmore » (>T2b). By Gleason score, 840 were low risk ({<=}6), 71 were intermediate risk (7), and 10 were high risk (>7). Patients were treated with brachytherapy only (I-125, n = 779, or Pd-103, n = 47), or brachytherapy + external-beam radiation therapy (n = 95). Median follow-up was 6.3 years. We noted whether nPSA <0.5 ng/mL was achieved and the time to achieve this nadir and tested for associations with pretreatment risk factors. We also determined whether this PSA endpoint was associated with decreased PSA failure or distant metastasis. Results: Absence of high-risk factors in clinical stage ({<=}T2b), Gleason score ({<=}7), and pretreatment PSA ({<=}20 ng/mL) was significantly associated with achieving nPSA <0.5 ng/mL. By Kaplan-Meier analysis, patients achieving nPSA <0.5 ng/mL had significantly higher long-term freedom from biochemical failure (FFBF) than nonresponders (5-year FFBF: 95.2 {+-} 0.8% vs. 71.5 {+-} 6.7%; p < 0.0005). Among responders, those who achieved nPSA <0.5 ng/mL in {<=}5 years had higher FFBF than those requiring >5 years (5-year FFBF: 96.7 {+-} 0.7% vs. 80.8 {+-} 4.6%; p < 0.0005). On multivariate analysis, patients who achieved nPSA <0.5 ng/mL in {<=}5 years had significantly higher FFBF than other patients. Conclusions: Pretreatment risk factors (clinical tumor stage, Gleason score, pretreatment PSA) strongly predict for patients achieving nPSA <0.5 ng/mL following brachytherapy, and this cohort had significantly higher long-term FFBF.« less

Long-term outcomes in younger men following permanent prostate brachytherapy.

PubMed

Shapiro, Edan Y; Rais-Bahrami, Soroush; Morgenstern, Carol; Napolitano, Barbara; Richstone, Lee; Potters, Louis

2009-04-01

We reviewed the long-term outcomes in men undergoing permanent prostate brachytherapy with a focus on those presenting before age 60 years. Between 1992 and 2005 a total of 2,119 patients with clinical stage T1-T2, N0, M0 prostate cancer treated with permanent prostate brachytherapy were included in this study. Treatment regimens consisted of permanent prostate brachytherapy with or without hormone therapy, permanent prostate brachytherapy with external beam radiotherapy, or all 3 modalities. Biochemical recurrence was defined using the Phoenix definition. Multivariate analysis was performed to determine if age and/or other clinicopathological features were associated with disease progression. The Kaplan-Meier method was used to calculate rates of freedom from progression with the log rank test to compare patients younger than 60 vs 60 years or older. Median followup was 56.1 months. In the study population 237 patients were younger than 60 years at diagnosis (11%). The 5 and 10-year freedom from progression rates were 90.1% and 85.6%, respectively, for the entire population. Multivariate analysis demonstrated that prostate specific antigen (p <0.01), biopsy Gleason score (p <0.0001) and year of treatment (p <0.001) were associated with freedom from progression while age (p = 0.95) and clinical stage (p = 0.11) were not. There was no significant difference in freedom from progression between men younger than 60, or 60 years or older (log rank p = 0.46). In the younger cohort the 10-year freedom from progression for patients presenting with low, intermediate and high risk disease was 91.3%, 80.0% and 70.2% compared to 91.8%, 83.4% and 72.1%, respectively, for men 60 years or older. Our long-term results confirm favorable outcomes after permanent prostate brachytherapy in men younger than 60 years. Outcomes are impacted by disease related risk factors but not by age or clinical stage. Definitive treatment options for younger men with clinically localized prostate cancer should include permanent prostate brachytherapy.

Antigen specific T-cell responses against tumor antigens are controlled by regulatory T cells in patients with prostate cancer.

PubMed

Hadaschik, Boris; Su, Yun; Huter, Eva; Ge, Yingzi; Hohenfellner, Markus; Beckhove, Philipp

2012-04-01

Immunotherapy is a promising approach in an effort to control castration resistant prostate cancer. We characterized tumor antigen reactive T cells in patients with prostate cancer and analyzed the suppression of antitumor responses by regulatory T cells. Peripheral blood samples were collected from 57 patients with histologically confirmed prostate cancer, 8 patients with benign prostatic hyperplasia and 16 healthy donors. Peripheral blood mononuclear cells were isolated and antigen specific interferon-γ secretion of isolated T cells was analyzed by enzyme-linked immunospot assay. T cells were functionally characterized and T-cell responses before and after regulatory T-cell depletion were compared. As test tumor antigens, a panel of 11 long synthetic peptides derived from a total of 8 tumor antigens was used, including prostate specific antigen and prostatic acid phosphatase. In patients with prostate cancer we noted a 74.5% effector T-cell response rate compared with only 25% in patients with benign prostatic hyperplasia and 31% in healthy donors. In most patients 2 or 3 tumor antigens were recognized. Comparing various disease stages there was a clear increase in the immune response against prostate specific antigens from intermediate to high risk tumors and castration resistant disease. Regulatory T-cell depletion led to a significant boost in effector T-cell responses against prostate specific antigen and prostatic acid phosphatase. Tumor specific effector T cells were detected in most patients with prostate cancer, especially those with castration resistant prostate cancer. Since effector T-cell responses against prostate specific antigens strongly increased after regulatory T-cell depletion, our results indicate that immunotherapy efficacy could be enhanced by decreasing regulatory T cells. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A Dose–Response Analysis of Biochemical Control Outcomes After {sup 125}I Monotherapy for Patients With Favorable-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiraishi, Yutaka, E-mail: shiraishi@rad.med.keio.ac.jp; Department of Radiology, National Hospital Organization Tokyo Medical Center, Tokyo; Yorozu, Atsunori

Purpose: To define the optimal dose for {sup 125}I prostate implants by correlating postimplantation dosimetry findings with biochemical failure and toxicity. Methods and Materials: Between 2003 and 2009, 683 patients with prostate cancer were treated with {sup 125}I prostate brachytherapy without supplemental external beam radiation therapy and were followed up for a median time of 80 months. Implant dose was defined as the D90 (the minimal dose received by 90% of the prostate) on postoperative day 1 and 1 month after implantation. Therefore, 2 dosimetric variables (day 1 D90 and day 30 D90) were analyzed for each patient. We investigated the dosemore » effects on biochemical control and toxicity. Results: The 7-year biochemical failure-free survival (BFFS) rate for the group overall was 96.4% according to the Phoenix definition. A multivariate analysis found day 1 D90 and day 30 D90 to be the most significant factors affecting BFFS. The cutoff points for day 1 D90 and day 30 D90, calculated from ROC curves, were 163 Gy and 175 Gy, respectively. By use of univariate analysis, various dosimetric cutoff points for day 30 D90 were tested. We found that day 30 D90 cutoff points from 130 to 180 Gy appeared to be good for the entire cohort. Greater D90s were associated with an increase in late genitourinary or gastrointestinal toxicity ≥ grade 2, but the increase was not statistically significant. Conclusions: Improvements in BFFS rates were seen with increasing D90 levels. Day 30 D90 doses of 130 to 180 Gy were found to serve as cutoff levels. For low-risk and low-tier intermediate-risk prostate cancer patients, high prostate D90s, even with doses exceeding 180 Gy, achieve better treatment results and are feasible.« less

Risk of Localized and Advanced Prostate Cancer Among Immigrants Versus Native-Born Swedish Men: A nation-wide, population-based study

PubMed Central

Loeb, Stacy; Drevin, Linda; Robinson, David; Holmberg, Erik; Carlsson, Sigrid; Lambe, Mats; Stattin, Pär

2016-01-01

Purpose Prostate cancer (PCa) incidence and prognosis vary geographically. We examined possible differences in PCa risk by clinical risk category between native-born and immigrant populations in Sweden. Our hypothesis was that lower PSA-testing uptake among foreign-born men would result in lower rates of localized disease, and similar or higher risk of metastatic disease. Methods Using the Prostate Cancer database Sweden (PCBaSe), we identified 117,328 men with PCa diagnosed from 1991–2008, of which 8,332 were foreign-born. For each case, 5 cancer-free matched controls were randomly selected from the population register. Conditional logistic regression was used to compare low-risk, intermediate-risk, high-risk, regionally metastatic, and distant metastatic PCa based upon region of origin. Results Across all risk categories, immigrants had significantly lower PCa risk than native-born Swedish men, except North Americans and Northern Europeans. The lowest PCa risk was observed in men from the Middle East, Southern Europe and Asia. Multivariable adjustment for socioeconomic factors and comorbidities did not materially change risk estimates. Older age at immigration and more recent arrival in Sweden were associated with lower PCa risk. Non-native men were less likely to be diagnosed with PCa through PSA-testing during a health check-up. Conclusions The risk for all stages of PCa was lower among first-generation immigrants to Sweden compared to native-born men. Older age at immigration and more recent immigration were associated with particularly low risks. Patterns of PSA testing appeared to only partly explain the differences in PCa risk, since immigrant men also had a lower risk of metastatic disease. PMID:23266834

Biological optimization of simultaneous boost on intra-prostatic lesions (DILs): sensitivity to TCP parameters.

PubMed

Azzeroni, R; Maggio, A; Fiorino, C; Mangili, P; Cozzarini, C; De Cobelli, F; Di Muzio, N G; Calandrino, R

2013-11-01

The aim of this investigation was to explore the potential of biological optimization in the case of simultaneous integrated boost on intra-prostatic dominant lesions (DIL) and evaluating the impact of TCP parameters uncertainty. Different combination of TCP parameters (TD50 and γ50 in the Poisson-like model), were considered for DILs and the prostate outside DILs (CTV) for 7 intermediate/high-risk prostate patients. The aim was to maximize TCP while constraining NTCPs below 5% for all organs at risk. TCP values were highly depending on the parameters used and ranged between 38.4% and 99.9%; the optimized median physical doses were in the range 94-116 Gy and 69-77 Gy for DIL and CTV respectively. TCP values were correlated with the overlap PTV-rectum and the minimum distance between rectum and DIL. In conclusion, biological optimization for selective dose escalation is feasible and suggests prescribed dose around 90-120 Gy to the DILs. The obtained result is critically depending on the assumptions concerning the higher radioresistence in the DILs. In case of very resistant clonogens into the DIL, it may be difficult to maximize TCP to acceptable levels without violating NTCP constraints. Copyright © 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walsh, Seán, E-mail: walshsharp@gmail.com; Department of Oncology, Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford OX3 7DQ; Roelofs, Erik

Purpose: A fully heterogeneous population averaged mechanistic tumor control probability (TCP) model is appropriate for the analysis of external beam radiotherapy (EBRT). This has been accomplished for EBRT photon treatment of intermediate-risk prostate cancer. Extending the TCP model for low and high-risk patients would be beneficial in terms of overall decision making. Furthermore, different radiation treatment modalities such as protons and carbon-ions are becoming increasingly available. Consequently, there is a need for a complete TCP model. Methods: A TCP model was fitted and validated to a primary endpoint of 5-year biological no evidence of disease clinical outcome data obtained frommore » a review of the literature for low, intermediate, and high-risk prostate cancer patients (5218 patients fitted, 1088 patients validated), treated by photons, protons, or carbon-ions. The review followed the preferred reporting item for systematic reviews and meta-analyses statement. Treatment regimens include standard fractionation and hypofractionation treatments. Residual analysis and goodness of fit statistics were applied. Results: The TCP model achieves a good level of fit overall, linear regression results in a p-value of <0.000 01 with an adjusted-weighted-R{sup 2} value of 0.77 and a weighted root mean squared error (wRMSE) of 1.2%, to the fitted clinical outcome data. Validation of the model utilizing three independent datasets obtained from the literature resulted in an adjusted-weighted-R{sup 2} value of 0.78 and a wRMSE of less than 1.8%, to the validation clinical outcome data. The weighted mean absolute residual across the entire dataset is found to be 5.4%. Conclusions: This TCP model fitted and validated to clinical outcome data, appears to be an appropriate model for the inclusion of all clinical prostate cancer risk categories, and allows evaluation of current EBRT modalities with regard to tumor control prediction.« less

3D MR-Spectroscopic Imaging Assessment of Metabolic Activity in the Prostate During the PSA 'Bounce' Following {sup 125}Iodine Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirilova, Anna; Damyanovich, Andrei; Crook, Juanita, E-mail: jcrook@bccancer.bc.c

2011-02-01

Purpose: A temporary increase in prostate-specific antigen (PSA) values is observed in 30%-40% of men following {sup 125} I brachytherapy (BT) for prostate cancer. We present the results of a study to characterize prostate metabolic activity during the PSA 'bounce' and to correlate metabolic changes with PSA levels using three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI). Methods and Materials: 3D-MRSI was performed in 24 patients during the PSA bounce. Eight of these had also had a baseline 3D-MRSI scan before BT for the purpose of tumor mapping. The 3D-MRSI was repeated at 6- and 12-month intervals, and PSA levels were monitoredmore » every 3 months. Twenty-one of the patients had favorable-risk prostate cancer, and 3 had intermediate risk. Results: The choline+creatine signal intensity, although markedly reduced, was observable following BT. Diffuse activity not corresponding to original biopsy-positive sites was observed in 22 cases, and 2 cases were documented to have local recurrence. No statistically significant correlation between metabolic activity and PSA levels at each interval was found. Conclusion: Post-BT prostate 3D-MRSI shows evidence of diffuse metabolic activity unrelated to residual malignancy. This supports the benign nature of the PSA bounce and suggests an inflammatory etiology. In the situation of a rising PSA, observation of focal activity on MRI/3D-MRSI could be a useful adjunct to suggest local recurrence at an earlier interval after brachytherapy when prostate biopsies would still be unhelpful. Longer follow-up is necessary to confirm the complex relationship between metabolic activity and PSA levels.« less

Targeted Androgen Pathway Suppression in Localized Prostate Cancer: A Pilot Study

PubMed Central

Mostaghel, Elahe A.; Nelson, Peter S.; Lange, Paul; Lin, Daniel W.; Taplin, Mary Ellen; Balk, Steven; Ellis, William; Kantoff, Philip; Marck, Brett; Tamae, Daniel; Matsumoto, Alvin M.; True, Lawrence D.; Vessella, Robert; Penning, Trevor; Hunter Merrill, Rachel; Gulati, Roman; Montgomery, Bruce

2014-01-01

Purpose Ligand-mediated activation of the androgen receptor (AR) is critical for prostate cancer (PCa) survival and proliferation. The failure to completely ablate tissue androgens may limit suppression of PCa growth. We evaluated combinations of CYP17A and 5-α-reductase inhibitors for reducing prostate androgen levels, AR signaling, and PCa volumes. Patients and Methods Thirty-five men with intermediate/high-risk clinically localized PCa were randomly assigned to goserelin combined with dutasteride (ZD), bicalutamide and dutasteride (ZBD), or bicalutamide, dutasteride, and ketoconazole (ZBDK) for 3 months before prostatectomy. Controls included patients receiving combined androgen blockade with luteinizing hormone-releasing hormone agonist and bicalutamide. The primary outcome measure was tissue dihydrotestosterone (DHT) concentration. Results Prostate DHT levels were substantially lower in all experimental arms (0.02 to 0.04 ng/g v 0.92 ng/g in controls; P < .001). The ZBDK group demonstrated the greatest percentage decline in serum testosterone, androsterone, and dehydroepiandrosterone sulfate (P < .05 for all). Staining for AR and the androgen-regulated genes prostate-specific antigen and TMPRSS2 was strongly suppressed in benign glands and moderately in malignant glands (P < .05 for all). Two patients had pathologic complete response, and nine had ≤ 0.2 cm3 of residual tumor (defined as a near-complete response), with the largest numbers of complete and near-complete responses in the ZBDK group. Conclusion Addition of androgen synthesis inhibitors lowers prostate androgens below that achieved with standard therapy, but significant AR signaling remains. Tissue-based analysis of steroids and AR signaling is critical to informing the search for optimal local and systemic control of high-risk prostate cancer. PMID:24323034

Initial brazilian experience in the treatment of localized prostate cancer using a new generation cryotechnology: feasibility study.

PubMed

Kim, Fernando J; Cerqueira, Michael A; Almeida, Jose C; Pompeo, Alexandre; Sehrt, David; Calheiros, Jose M; Martins, Fernando A; Molina, Wilson R

2012-01-01

The objective of our study is to present the first Brazilian cryoablation experience in the treatment of low and intermediate risk localized prostate cancer using 3rd generation cryoablation and real-time biplanar transrectal ultrasonography. Ten Brazilian patients underwent primary cryoablation for localized prostate cancer between October 2010 and June 2011. All patients consented for whole gland primary cryotherapy. The procedures were performed by 3rd generation cryoablation with the Cryocare System ® (Endocare, Irvine, California). Preoperative data collection included patient demographics along with prostate gland size, Gleason score, serum prostate specific antigen, and erectile function status. Operative and post--operative assessment involved estimated blood loss, operative time, complications, serum PSA level, erectile function status, urinary incontinence, biochemical disease free survival (BDFS), and follow-up time. All patients in the study successfully underwent whole gland cryoablation. The mean of: age, prostate size, PSA level, and Gleason score, was 66.2 years old; 40.7 g; 7.8 ng/mL; and 6 respectively. All patients were classified as low or moderate D' Amico risk (5 low and 5 moderate). Erectile dysfunction was present in 50% of patients. The estimated blood loss was minimal, operative time was 46.1 minutes. All patients that developed erectile dysfunction post-treatment responded to oral or intracavernosal medications with early penile rehabilitation. All patients maintained urinary continence by the end of a 10 months evaluation period and none had biochemical relapse within the mean follow-up of 13 months (7-15 months). Our initial experience shows that cryoablation is a minimally invasive option for the treatment of localized prostate cancer. Short term data seems to be promising but longer follow-up is necessary to verify oncological and functional results.

Application of Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2): Interobserver Agreement and Positive Predictive Value for Localization of Intermediate- and High-Grade Prostate Cancers on Multiparametric Magnetic Resonance Imaging.

PubMed

Chen, Frank; Cen, Steven; Palmer, Suzanne

2017-09-01

To evaluate interobserver agreement with the use of and the positive predictive value (PPV) of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) for the localization of intermediate- and high-grade prostate cancers on multiparametric magnetic resonance imaging (mpMRI). In this retrospective, institutional review board-approved study, 131 consecutive patients who had mpMRI followed by transrectal ultrasound-MR imaging fusion-guided biopsy of the prostate were included. Two readers who were blinded to initial mpMRI reports, clinical data, and pathologic outcomes reviewed the MR images, identified all prostate lesions, and scored each lesion based on the PI-RADS v2. Interobserver agreement was assessed by intraclass correlation coefficient (ICC), and PPV was calculated for each PI-RADS category. PI-RADS v2 was found to have a moderate level of interobserver agreement between two readers of varying experience, with ICC of 0.74, 0.72, and 0.67 for all lesions, peripheral zone lesions, and transitional zone lesions, respectively. Despite only moderate interobserver agreement, the calculated PPV in the detection of intermediate- and high-grade prostate cancers for each PI-RADS category was very similar between the two readers, with approximate PPV of 0%, 12%, 64%, and 87% for PI-RADS categories 2, 3, 4, and 5, respectively. In our study, PI-RADS v2 has only moderate interobserver agreement, a similar finding in studies of the original PI-RADS and in initial studies of PI-RADS v2. Despite this, PI-RADS v2 appears to be a useful system to predict significant prostate cancer, with PI-RADS scores correlating well with the likelihood of intermediate- and high-grade cancers. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Magnetic resonance/transrectal ultrasound fusion biopsy of the prostate compared to systematic 12-core biopsy for the diagnosis and characterization of prostate cancer: multi-institutional retrospective analysis of 389 patients.

PubMed

Mariotti, Guilherme C; Costa, Daniel N; Pedrosa, Ivan; Falsarella, Priscila M; Martins, Tatiana; Roehrborn, Claus G; Rofsky, Neil M; Xi, Yin; M Andrade, Thais C; Queiroz, Marcos R; Lotan, Yair; Garcia, Rodrigo G; Lemos, Gustavo C; Baroni, Ronaldo H

2016-09-01

To determine the incremental diagnostic value of targeted biopsies added to an extended sextant biopsy scheme on a per-patient, risk-stratified basis in 2 academic centers using different multiparametric magnetic resonance imaging (MRI) protocols, a large group of radiologists, multiple biopsy systems, and different biopsy operators. All patients with suspected prostate cancer (PCa) who underwent multiparametric MRI of the prostate in 2 academic centers between February 2013 and January 2015 followed by systematic and targeted MRI-transrectal ultrasound fusion biopsy were reviewed. Risk-stratified detection rate using systematic biopsies was compared with targeted biopsies on a per-patient basis. The McNemar test was used to compare diagnostic performance of the 2 approaches. A total of 389 men met eligibility criteria. PCa was diagnosed in 47% (182/389), 52%(202/389), and 60%(235/389) of patients using the targeted, systematic, and combined (targeted plus systematic) approach, respectively. Compared with systematic biopsy, targeted biopsy diagnosed 11% (37 vs. 26) more intermediate-to-high risk (P<0.0001) and 16% (10 vs. 16) fewer low-risk tumors (P<0.0001). These results were replicated when data from each center, biopsy-naïve patients, and men with previous negative biopsies were analyzed separately. Targeted MRI-transrectal ultrasound fusion biopsy consistently improved the detection of clinically significant PCa in a large patient cohort with diverse equipment, protocols, radiologists, and biopsy operators as can be encountered in clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Prostate intensity-modulated radiotherapy planning in seven mouse clicks: Development of a class solution for cancer.

PubMed

Wood, Maree; Fonseca, Amara; Sampson, David; Kovendy, Andrew; Westhuyzen, Justin; Shakespeare, Thomas; Turnbull, Kirsty

2016-01-01

The aim of the retrospective study was to develop a planning class solution for prostate intensity-modulated radiotherapy (IMRT) that achieved target and organs-at-risk (OAR) doses within acceptable departmental protocol criteria using the Monaco treatment planning system (Elekta-CMS Software, MO, USA). Advances in radiation therapy technology have led to a re-evaluation of work practices. Class solutions have the potential to produce highly conformal plans in a time-efficient manner. Using data from intermediate and high risk prostate cancer patients, a stepwise quality improvement model was employed. Stage 1 involved the development of a broadly based treatment template developed across 10 patients. Stage 2 involved template refinement and clinical audit ( n  = 20); Stage 3, template review ( n  = 50) and Stage 4 an assessment of a revised template against the actual treatment plan involving 72 patients. The computer algorithm that comprised the Stage 4 template met clinical treatment criteria for 82% of patients. Minor template changes were required for a further 13% of patients. Major changes were required in 4%; one patient could not be assessed. The average calculation time was 13 min and involved seven mouse clicks by the planner. Thus, the new template met treatment criteria or required only minor changes in 95% of prostate patients; this is an encouraging result suggesting improvements in planning efficiency and consistency. It is feasible to develop a class solution for prostate IMRT using a stepwise quality improvement model which delivers clinically acceptable plans in the great majority of prostate cases.

Pelvic Nodal Radiotherapy in Patients With Unfavorable Intermediate and High-Risk Prostate Cancer: Evidence, Rationale, and Future Directions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morikawa, Lisa K.; Memorial Sloan-Kettering Cancer Center; Roach, Mack, E-mail: mroach@radonc.ucsf.ed

2011-05-01

Over the past 15 years, there have been three major advances in the use of external beam radiotherapy in the management of men with clinically localized prostate made. They include: (1) image guided (IG) three-dimensional conformal/intensity modulated radiotherapy; (2) radiation dose escalation; and (3) androgen deprivation therapy. To date only the last of these three advances have been shown to improve overall survival. The presence of occult pelvic nodal involvement could explain the failure of increased conformality and dose escalation to prolong survival, because the men who appear to be at the greatest risk of death from clinically localized prostatemore » cancer are those who are likely to have lymph node metastases. This review discusses the evidence for prophylactic pelvic nodal radiotherapy, including the key trials and controversies surrounding this issue.« less

Concurrent Androgen Deprivation Therapy During Salvage Prostate Radiotherapy Improves Treatment Outcomes in High-Risk Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soto, Daniel E., E-mail: dsoto2@partners.org; Passarelli, Michael N.; Daignault, Stephanie

2012-03-01

Purpose: To determine whether concurrent androgen deprivation therapy (ADT) during salvage radiotherapy (RT) improves prostate cancer treatment outcomes. Methods and Materials: A total of 630 postprostatectomy patients were retrospectively identified who were treated with three-dimensional conformal RT. Of these, 441 were found to be treated for salvage indications. Biochemical failure was defined as prostate-specific antigen (PSA) of 0.2 ng/mL or greater above nadir with another PSA increase or the initiation of salvage ADT. Progression-free survival (PFS) was defined as the absence of biochemical failure, continued PSA rise despite salvage therapy, initiation of systemic therapy, clinical progression, or distant failure. Multivariate-adjustedmore » Cox proportional hazards modeling was performed to determine which factors predict PFS. Results: Low-, intermediate-, and high-risk patients made up 10%, 24%, and 66% of patients, respectively. The mean RT dose was 68 Gy. Twenty-four percent of patients received concurrent ADT (cADT). Regional pelvic nodes were treated in 16% of patients. With a median follow-up of 3 years, the 3-year PFS was 4.0 years for cADT vs. 3.4 years for cADT patients (p = 0.22). Multivariate analysis showed that concurrent ADT (p = 0.05), Gleason score (p < 0.001), and pre-RT PSA (p = 0.03) were independent predictors of PFS. When patients were stratified by risk group, the benefits of cADT (hazard ratio, 0.65; p = 0.046) were significant only for high-risk patients. Conclusions: This retrospective study showed a PFS benefit of concurrent ADT during salvage prostate RT. This benefit was observed only in high-risk patients.« less

Australian validation of the Cancer of the Prostate Risk Assessment Post-Surgical score to predict biochemical recurrence after radical prostatectomy.

PubMed

Beckmann, Kerri; O'Callaghan, Michael; Vincent, Andrew; Roder, David; Millar, Jeremy; Evans, Sue; McNeil, John; Moretti, Kim

2018-03-01

The Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) score is a simple post-operative risk assessment tool predicting disease recurrence after radical prostatectomy, which is easily calculated using available clinical data. To be widely useful, risk tools require multiple external validations. We aimed to validate the CAPRA-S score in an Australian multi-institutional population, including private and public settings and reflecting community practice. The study population were all men on the South Australian Prostate Cancer Clinical Outcomes Collaborative Database with localized prostate cancer diagnosed during 1998-2013, who underwent radical prostatectomy without adjuvant therapy (n = 1664). Predictive performance was assessed via Kaplan-Meier and Cox proportional regression analyses, Harrell's Concordance index, calibration plots and decision curve analysis. Biochemical recurrence occurred in 342 (21%) cases. Five-year recurrence-free probabilities for CAPRA-S scores indicating low (0-2), intermediate (3-5) and high risk were 95, 79 and 46%, respectively. The hazard ratio for CAPRA-S score increments was 1.56 (95% confidence interval 1.49-1.64). The Concordance index for 5-year recurrence-free survival was 0.77. The calibration plot showed good correlation between predicted and observed recurrence-free survival across scores. Limitations include the retrospective nature and small numbers with higher CAPRA-S scores. The CAPRA-S score is an accurate predictor of recurrence after radical prostatectomy in our cohort, supporting its utility in the Australian setting. This simple tool can assist in post-surgical selection of patients who would benefit from adjuvant therapy while avoiding morbidity among those less likely to benefit. © 2017 Royal Australasian College of Surgeons.

High-intensity focused ultrasound (HIFU) using Sonablate{trade mark, serif} devices for the treatment of localized prostate cancer: 13-year experience

NASA Astrophysics Data System (ADS)

Uchida, Toyoaki; Tomonaga, Tetsuro; Shoji, Sunao; Kim, Hakushi; Nagata, Yoshihiro

2012-11-01

To report on the long-term results of high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. Eight hundred and eighty-four men with prostate cancer treated with Sonablate® (SB) devices were included. All patients were followed for more than 2 years. The patients were divided into three groups: in the first group, 419 patients were treated with SB200/500 from 1999 to 2006; in the second group, 263 patients were treated with SB 500 ver. 4 from 2005 to 2009: in the third group, 202 patients were treated with SB 500 TCM from 2007 up to present. Biochemical failure was defined according to the Phoenix definition (PSA nadir + 2 ng/ml). The mean age, PSA, Gleason score, operation time, and follow-up period in each group were 68, 66 and 67 years, 11.2, 9.7 and 9.3 ng/ml, 6.2, 6.6 and 6.7, 167, 101 and 106 min, and 56, 48 and 36 months, respectively. The biochemical disease-free rate (bDFR) in each group at 5 years was, respectively, 54%, 61% and 84%, and was 50% at 10 years in the SB200/500 group (p<0.0001). The bDFR in patients in the low-, intermediate-, and high-risk groups in all patients at 10 years were 72% and 58%, 44%, respectively (p<0.0001). The BDFR in patients in the low-, intermediate-, and high-risk groups in the SB500 TCM group at 5 years were 97%, 83%, and 74% (p=0.0056). The negative prostate biopsy rates in 3 groups were 81%, 92% and 88%, respectively. As post HIFU complications, urethral stricture, acute epididymitis and urinary incontinence were noted in 18.0%, 6.2% and 1.9%, respectively. Rectourethral fistula was occurred in 0.6% in the first HIFU cases, Postoperative erectile dysfunction was noted in 27% of patients at 2 years after HIFU. HIFU therapy appears to be minimally invasive, efficacious, and safe for patients with localized prostate cancer. Technological advances as well as cultural and economic vectors have caused a shift from to minimally invasive techniques.

Comparison of 68Ga-PSMA-11 PET-CT with mpMRI for preoperative lymph node staging in patients with intermediate to high-risk prostate cancer.

PubMed

Zhang, Qing; Zang, Shiming; Zhang, Chengwei; Fu, Yao; Lv, Xiaoyu; Zhang, Qinglei; Deng, Yongming; Zhang, Chuan; Luo, Rui; Zhao, Xiaozhi; Wang, Wei; Wang, Feng; Guo, Hongqian

2017-11-07

To evaluate the diagnostic value of 68 Ga-PSMA-11 PET-CT with multiparametric magnetic resonance imaging (mpMRI) for lymph node (LN) staging in patients with intermediate- to high-risk prostate cancer (PCa) undergoing radical prostatectomy (RP) with pelvic lymph node dissection (PLND). We retrospectively identified 42 consecutive patients with intermediate- to high-risk PCa according to D'Amico and without concomitant cancer. Preoperative 68 Ga-PSMA-11 PET-CT, pelvic mpMRI and subsequent robot assisted laparoscopic RP with PLND were performed in all patients. Among 42 patients assessed, the preoperative PSA value, Gleason score, pT stage and intraprostatic PCa volume of patients with LN metastases were all significantly higher than those without metastases (P = 0.029, 0.028, 0.004, respectively). The average maximum standardized uptake value (SUV) of 68 Ga-PSMA-11 PET-CT positive PCa of patients with or without LN metastases were 13.10 (range 6.12-51.75) and 7.22 (range 5.4-11.2), respectively (P < 0.001). 68 Ga-PSMA-11 PET-CT and pelvic mpMRI had the ability of succeed on preoperative definite accurate diagnosis and accurate localization of primary PCa in all 42 patients. Fifteen patients (35.71%) had a pN1 stage. 51 positive LN were found. Both 68 Ga-PSMA-11 PET-CT and pelvic mpMRI displayed brillient patient-based and region-based sensitivity, specificity, negative predictive value and positive predictive value. There was no statistical difference for the detection of LNMs according to the diameter of the LNMs between 68 Ga-PSMA-11 PET-CT and mpMRI in this study. Both 68 Ga-PSMA-11 PET-CT and mpMRI performed great value for LN staging in patients with intermediate- to high-risk PCa undergoing RP with PLND. However, despite excellent performance of 68 Ga-PSMA-11 PET-CT, it cannot replace mpMRI that remains excellent for lymph node staging.

Evaluation of high intensity focused ultrasound ablation of prostate tumor with hyperpolarized 13C imaging biomarkers

NASA Astrophysics Data System (ADS)

Lee, Jessie E.; Diederich, Chris J.; Salgaonkar, Vasant A.; Bok, Robert; Taylor, Andrew G.; Kurhanewicz, John

2015-03-01

Real-time hyperpolarized (HP) 13C MR can be utilized during high-intensity focal ultrasound (HIFU) therapy to improve treatment delivery strategies, provide treatment verification, and thus reduce the need for more radical therapies for lowand intermediate-risk prostate cancers. The goal is to develop imaging biomarkers specific to thermal therapies of prostate cancer using HIFU, and to predict the success of thermal coagulation and identify tissues potentially sensitized to adjuvant treatment by sub-ablative hyperthermic heat doses. Mice with solid prostate tumors received HIFU treatment (5.6 MHz, 160W/cm2, 60 s), and the MR imaging follow-ups were performed on a wide-bore 14T microimaging system. 13C-labeled pyruvate and urea were used to monitor tumor metabolism and perfusion accordingly. After treatment, the ablated tumor tissue had a loss in metabolism and perfusion. In the regions receiving sub-ablative heat dose, a timedependent change in metabolism and perfusion was observed. The untreated regions behaved as a normal untreated TRAMP prostate tumor would. This promising preliminary study shows the potential of using 13C MR imaging as biomarkers of HIFU/thermal therapies.

Screening and Characterization of a Novel RNA Aptamer That Specifically Binds to Human Prostatic Acid Phosphatase and Human Prostate Cancer Cells

PubMed Central

Kong, Hoon Young; Byun, Jonghoe

2015-01-01

Prostatic acid phosphatase (PAP) expression increases proportionally with prostate cancer progression, making it useful in prognosticating intermediate to high-risk prostate cancers. A novel ligand that can specifically bind to PAP would be very helpful for guiding prostate cancer therapy. RNA aptamers bind to target molecules with high specificity and have key advantages such as low immunogenicity and easy synthesis. Here, human PAP-specific aptamers were screened from a 2′-fluoropyrimidine (FY)-modified RNA library by SELEX. The candidate aptamer families were identified within six rounds followed by analysis of their sequences and PAP-specific binding. A gel shift assay was used to identify PAP binding aptamers and the 6N aptamer specifically bound to PAP with a Kd value of 118 nM. RT-PCR and fluorescence labeling analyses revealed that the 6N aptamer bound to PAP-positive mammalian cells, such as PC-3 and LNCaP. IMR-90 negative control cells did not bind the 6N aptamer. Systematic minimization analyses revealed that 50 nucleotide sequences and their two hairpin structures in the 6N 2′-FY RNA aptamer were equally important for PAP binding. Renewed interest in PAP combined with the versatility of RNA aptamers, including conjugation of anti-cancer drugs and nano-imaging probes, could open up a new route for early theragnosis of prostate cancer. PMID:25591398

Magnetic resonance imaging in active surveillance—a modern approach

PubMed Central

Moore, Caroline M.

2018-01-01

In recent years, active surveillance has been increasingly adopted as a conservative management approach to low and sometimes intermediate risk prostate cancer, to avoid or delay treatment until there is evidence of higher risk disease. A number of studies have investigated the role of multiparametric magnetic resonance imaging (mpMRI) in this setting. MpMRI refers to the use of multiple MRI sequences (T2-weighted anatomical and functional imaging which can include diffusion-weighted imaging, dynamic contrast enhanced imaging, spectroscopy). Each of the parameters investigates different aspects of the prostate gland (anatomy, cellularity, vascularity, etc.). In addition to a qualitative assessment, the radiologist can also extrapolate quantitative imaging biomarkers from these sequences, for example the apparent diffusion coefficient from diffusion-weighted imaging. There are many different types of articles (e.g., reviews, commentaries, consensus meetings, etc.) that address the use of mpMRI in men on active surveillance for prostate cancer. In this paper, we compare original articles that investigate the role of the different mpMRI sequences in men on active surveillance for prostate cancer, in order to discuss the relative utility of the different sequences, and combinations of sequences. We searched MEDLINE/PubMed for manuscripts published from inception to 1st December 2017. The search terms used were (prostate cancer or prostate adenocarcinoma or prostatic carcinoma or prostate carcinoma or prostatic adenocarcinoma) and (MRI or NMR or magnetic resonance imaging or mpMRI or multiparametric MRI) and active surveillance. Overall, 425 publications were found. All abstracts were reviewed to identify papers with original data. Twenty-five papers were analysed and summarised. Some papers based their analysis only on one mpMRI sequence, while others assessed two or more. The evidence from this review suggests that qualitative assessments and quantitative data from different mpMRI sequences hold promise in the management of men on active surveillance for prostate cancer. Both qualitative and quantitative approaches should be considered when assessing mpMRI of the prostate. There is a need for robust studies assessing the relative utility of different combinations of sequences in a systematic manner to determine the most efficient use of mpMRI in men on active surveillance. PMID:29594026

High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barkati, Maroie; Williams, Scott G., E-mail: scott.williams@petermac.org; Department of Pathology, University of Melbourne, Melbourne

Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3more » fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable-risk prostate cancer, administered using a single implant over 2 days, is feasible and has acceptable acute and late toxicities. Further follow-up is still required to better evaluate the efficacy of such treatment.« less

Five-Year Biochemical Results, Toxicity, and Patient-Reported Quality of Life After Delivery of Dose-Escalated Image Guided Proton Therapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bryant, Curtis, E-mail: cbryant@floridaproton.org; Smith, Tamara L.; Henderson, Randal H.

Purpose: To report clinical outcomes in patients treated with image guided proton therapy (PT) for localized prostate cancer. Methods and Materials: The medical records of 1327 men were reviewed. Each man was enrolled on an outcomes tracking study. Dual enrollment on a prospective clinical trial was allowed. Each patient was treated for localized prostate cancer with PT at our institution between 2006 and 2010. Ninety-eight percent of patients received 78 Gy (radiobiological equivalent [RBE]) or higher; 18% received androgen deprivation therapy (ADT). The 5-year freedom from biochemical progression (FFBP), distant metastasis-free survival, and cause-specific survival rates are reported for each risk group. Datamore » on patient-reported quality of life and high-grade toxicities were prospectively collected and reported. A multivariate analysis was performed to identify clinical predictors of biochemical failure and urologic toxicity. Results: The median follow-up time was 5.5 years. The 5-year FFBP rates were 99%, 94%, and 74% in low-risk, intermediate-risk, and high-risk patients, respectively. The actuarial 5-year rates of late grade 3+ Common Terminology Criteria for Adverse Events, version 4.0, gastrointestinal (GI) and genitourinary (GU) toxicity were 0.6% and 2.9%, respectively. Multivariate analysis showed a significant correlation between grade 3+ GU toxicity and pretreatment prostate reductive procedures (P<.0001), prostate volume (P=.0085), pretreatment α-blockers (P=.0067), diabetes (P=.0195), and dose–volume histogram parameters (P=.0208). The median International Prostate Symptom Scores pretreatment scores and scores at 5 years after treatment were 7 and 7, respectively. The mean Expanded Prostate Cancer Index Composite (EPIC) scores significantly declined for sexual summary for patients not receiving ADT (from 67 to 53) between baseline and 5 years. Conclusions: Image guided PT provided excellent biochemical control rates for patients with localized prostate cancer. The actuarial rates of high-grade toxicity were low after PT. From pretreatment to 5 years of follow-up, a significant decline was found only in mean EPIC sexual summary scores. Prospective clinical studies are needed to determine the comparative effectiveness of PT and other radiation treatment strategies.« less

Single center experience with third-generation cryosurgery for management of organ-confined prostate cancer: critical evaluation of short-term outcomes, complications, and patient quality of life.

PubMed

Hubosky, Scott G; Fabrizio, Michael D; Schellhammer, Paul F; Barone, Bethany B; Tepera, Christopher M; Given, Robert W

2007-12-01

Technical refinements such as improved ultrasonographic localization and the routine use of urethral warmers and small-gauge needle delivery systems have renewed interest in cryosurgical treatment as a minimally invasive option for selected patients with localized prostate cancer. Only three reports of quality of life (QoL) in prostate cryoablation exist, and none report on patients treated with third-generation cryoablative technology. We critically examine our initial series of consecutive patients at a single institution undergoing primary third-generation cryosurgical treatment of localized prostate cancer with respect to treatment outcome, morbidity profile, and QoL parameters. To our knowledge, this is the first QoL report on third-generation cryoablation of the prostate. We retrospectively review the records of 89 consecutive patients with median followup of 11 months (1-32) who have undergone third-generation cryosurgical ablation of the prostate as primary treatment for localized prostate cancer with intention to cure. Patients were risk stratified according to preprocedural parameters of prostate-specific antigen (PSA), clinical stage, and Gleason score. PSA trends were recorded and treatment effectiveness was observed using different definitions of biochemical failure. Charts were reviewed for postprocedure complications. Quality of life was measured prospectively using the University of California, Los Angeles, Prostate Cancer Index as well as American Urological Association symptom scores. We compare a percent of baseline score (%BS) for various domains between our series of patients treated with primary cryoablation with a series of patients undergoing brachytherapy for localized prostate cancer. Treatment success was defined by achievement of a PSA nadir of < or =0.1 ng/mL and by biochemical disease-free survival (BDFS) assessed with both a PSA threshold of < or =0.4 ng/dL over time and the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of three consecutive rises in PSA. According to risk stratification, 86%, 81.5%, and 78% of low-, intermediate-, and high-risk patients, respectively, achieved a PSA nadir of < or =0.1 ng/mL. Overall, at 12 months follow-up, 94% of patients achieved BDFS using ASTRO criteria while 70% achieved BDFS using a PSA threshold of < or =0.4 ng/mL. With risk stratification, 74%, 70%, and 60% of low-, intermediate-, and high-risk patients, respectively, achieved BDFS defined by PSA threshold of < or =0.4 ng/mL. Complications were rare. The response rate for Health Related Quality of Life (HRQoL) questionnaires was 71% for cryoablation patients and 51% for brachytherapy patients. At 12 months follow-up, patients undergoing cryoablation on average achieved urinary and bowel domain scores comparable to baseline, but sexual domains remained well below baseline. When compared with a brachytherapy series with better baseline sexual function (P = 0.04) and urinary function (P = 0.03), cryotherapy patients experienced more negative impact on sexual function steadily for up to 12 months (P = 0.02). Urinary function was similar between the groups until 18 months, at which time cryoablation patients fared better (P = 0.01); this was sustained up to 24 months (P = 0.04). Treatment success with cryosurgery varies with definition; however, our results are comparable to other series with regard to short-term cancer control. Complication rates in this series of third-generation cryosurgical patients are low. QoL characteristics of third-generation cryoablation are similar to those described in second-generation cryoablation series. Compared with brachytherapy, cryotherapy results in less irritative and obstructive voiding symptoms in the early post-treatment period and may improve urinary function up to 24 months after treatment. In a small group of older patients with baseline erectile dysfunction undergoing cryoablation, sexual function returns to 20% of its baseline value with up to 12 months follow-up.

Utility of Risk Models in Decision Making After Radical Prostatectomy: Lessons from a Natural History Cohort of Intermediate- and High-Risk Men.

PubMed

Ross, Ashley E; Yousefi, Kasra; Davicioni, Elai; Ghadessi, Mercedeh; Johnson, Michael H; Sundi, Debasish; Tosoian, Jeffery J; Han, Misop; Humphreys, Elizabeth B; Partin, Alan W; Walsh, Patrick C; Trock, Bruce J; Schaeffer, Edward M

2016-03-01

Current guidelines suggest adjuvant radiation therapy for men with adverse pathologic features (APFs) at radical prostatectomy (RP). We examine at-risk men treated only with RP until the time of metastasis. To evaluate whether clinicopathologic risk models can help guide postoperative therapeutic decision making. Men with National Comprehensive Cancer Network intermediate- or high-risk localized prostate cancer undergoing RP in the prostate-specific antigen (PSA) era were identified (n=3089). Only men with initial undetectable PSA after surgery and who received no therapy prior to metastasis were included. APFs were defined as pT3 disease or positive surgical margins. Area under the receiver operating characteristic curve (AUC) for time to event data was used to measure the discrimination performance of the risk factors. Cumulative incidence curves were constructed using Fine and Gray competing risks analysis to estimate the risk of biochemical recurrence (BCR) or metastasis, taking censoring and death due to other causes into consideration. Overall, 43% of the cohort (n=1327) had APFs at RP. Median follow-up for censored patients was 5 yr. Cumulative incidence of metastasis was 6% at 10 yr after RP for all patients. Cumulative incidence of metastasis among men with APFs was 7.5% at 10 yr after RP. Among men with BCR, the incidence of metastasis was 38% 5 yr after BCR. At 10 yr after RP, time-dependent AUC for predicting metastasis by Cancer of the Prostate Risk Assessment Postsurgical or Eggener risk models was 0.81 (95% confidence interval [CI], 0.72-0.97) and 0.78 (95% CI, 0.67-0.97) in the APF population, respectively. At 5 yr after BCR, these values were lower (0.58 [95% CI, 0.50-0.66] and 0.70 [95% CI, 0.63-0.76]) among those who developed BCR. Use of risk model cut points could substantially reduce overtreatment while minimally increasing undertreatment (ie, use of an Eggener cut point of 2.5% for treatment of men with APFs would spare 46% from treatment while only allowing for metastatic events in 1% at 10 yr after RP). Use of risk models reduces overtreatment and should be a routine part of patient counseling when considering adjuvant therapy. Risk model performance is significantly reduced among men with BCR. Use of current risk models can help guide decision making regarding therapy after surgery and reduce overtreatment. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Intermediate-term efficacy of Tm:YAG laser prostate vaporesection for bladder outlet obstruction: initial experience from a UK teaching hospital.

PubMed

Pal, Raj P; Khan, Masood A

2012-01-01

To assess the safety and clinical efficacy of Tm:YAG laser vaporesection of the prostate (ThuVaRP) at intermediate-term follow-up. We identified the first 60 consecutive patients who underwent ThuVaRP at our institute. Operative outcomes assessed were resection time, resection weight, drop in haemoglobin, transfusion rate, catheter time and complication rate. The International Prostate Symptom Score (IPSS) was documented at a mean follow-up period of 19 months postoperatively. 45/60 patients underwent treatment due to lower urinary tract symptoms secondary to benign prostatic obstruction, 11/60 patients had a long-term catheter in situ for refractory urinary retention secondary to benign prostatic obstruction, and 4/60 patients had bladder outflow obstruction secondary to adenocarcinoma of the prostate. 1/60 patients developed urosepsis, 1/60 patients developed a urinary tract infection and 1/60 patients required 3-way catheterization and irrigation due to haematuria. No patients required a blood transfusion. The mean IPSS at a mean follow-up interval of 19 months (range 15-28 months) was 5.1 (range 1-23). Postoperative maximum flow rate improved from 7.9 to 17.1 ml/s, and post-micturition residual volume decreased from 254 to 86 ml. ThuVaRP is safe and appears to have durable efficacy at intermediate follow-up. Copyright © 2011 S. Karger AG, Basel.

Meta-analysis of studies comparing oncologic outcomes of radical prostatectomy and brachytherapy for localized prostate cancer

PubMed Central

Cozzi, Gabriele; Musi, Gennaro; Bianchi, Roberto; Bottero, Danilo; Brescia, Antonio; Cioffi, Antonio; Cordima, Giovanni; Delor, Maurizio; Di Trapani, Ettore; Ferro, Matteo; Matei, Deliu Victor; Russo, Andrea; Mistretta, Francesco Alessandro; De Cobelli, Ottavio

2017-01-01

Background: The aim of this study was to compare oncologic outcomes of radical prostatectomy (RP) with brachytherapy (BT). Methods: A literature review was conducted according to the ‘Preferred reporting items for systematic reviews and meta-analyses’ (PRISMA) statement. We included studies reporting comparative oncologic outcomes of RP versus BT for localized prostate cancer (PCa). From each comparative study, we extracted the study design, the number and features of the included patients, and the oncologic outcomes expressed as all-cause mortality (ACM), PCa-specific mortality (PCSM) or, when the former were unavailable, as biochemical recurrence (BCR). All of the data retrieved from the selected studies were recorded in an electronic database. Cumulative analysis was conducted using the Review Manager version 5.3 software, designed for composing Cochrane Reviews (Cochrane Collaboration, Oxford, UK). Statistical heterogeneity was tested using the Chi-square test. Results: Our cumulative analysis did not show any significant difference in terms of BCR, ACM or PCSM rates between the RP and BT cohorts. Only three studies reported risk-stratified outcomes of intermediate- and high-risk patients, which are the most prone to treatment failure. Conclusions: our analysis suggested that RP and BT may have similar oncologic outcomes. However, the analysis included a limited number of studies, and most of them were retrospective, making it impossible to derive any definitive conclusion, especially for intermediate- and high-risk patients. In this scenario, appropriate urologic counseling remains of utmost importance. PMID:29662542

Meta-analysis of studies comparing oncologic outcomes of radical prostatectomy and brachytherapy for localized prostate cancer.

PubMed

Cozzi, Gabriele; Musi, Gennaro; Bianchi, Roberto; Bottero, Danilo; Brescia, Antonio; Cioffi, Antonio; Cordima, Giovanni; Delor, Maurizio; Di Trapani, Ettore; Ferro, Matteo; Matei, Deliu Victor; Russo, Andrea; Mistretta, Francesco Alessandro; De Cobelli, Ottavio

2017-11-01

The aim of this study was to compare oncologic outcomes of radical prostatectomy (RP) with brachytherapy (BT). A literature review was conducted according to the 'Preferred reporting items for systematic reviews and meta-analyses' (PRISMA) statement. We included studies reporting comparative oncologic outcomes of RP versus BT for localized prostate cancer (PCa). From each comparative study, we extracted the study design, the number and features of the included patients, and the oncologic outcomes expressed as all-cause mortality (ACM), PCa-specific mortality (PCSM) or, when the former were unavailable, as biochemical recurrence (BCR). All of the data retrieved from the selected studies were recorded in an electronic database. Cumulative analysis was conducted using the Review Manager version 5.3 software, designed for composing Cochrane Reviews (Cochrane Collaboration, Oxford, UK). Statistical heterogeneity was tested using the Chi-square test. Our cumulative analysis did not show any significant difference in terms of BCR, ACM or PCSM rates between the RP and BT cohorts. Only three studies reported risk-stratified outcomes of intermediate- and high-risk patients, which are the most prone to treatment failure. our analysis suggested that RP and BT may have similar oncologic outcomes. However, the analysis included a limited number of studies, and most of them were retrospective, making it impossible to derive any definitive conclusion, especially for intermediate- and high-risk patients. In this scenario, appropriate urologic counseling remains of utmost importance.

Sci—Fri PM: Topics — 04: What if bystander effects influence cell kill within a target volume? Potential consequences of dose heterogeneity on TCP and EUD on intermediate risk prostate patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balderson, M.J.; Kirkby, C.; Department of Medical Physics, Tom Baker Cancer Centre, Calgary, Alberta

In vitro evidence has suggested that radiation induced bystander effects may enhance non-local cell killing which may influence radiotherapy treatment planning paradigms. This work applies a bystander effect model, which has been derived from published in vitro data, to calculate equivalent uniform dose (EUD) and tumour control probability (TCP) and compare them with predictions from standard linear quadratic (LQ) models that assume a response due only to local absorbed dose. Comparisons between the models were made under increasing dose heterogeneity scenarios. Dose throughout the CTV was modeled with normal distributions, where the degree of heterogeneity was then dictated by changingmore » the standard deviation (SD). The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. The bystander model suggests a moderate degree of dose heterogeneity yields as good or better outcome compared to a uniform dose in terms of EUD and TCP. Intermediate risk prostate prescriptions of 78 Gy over 39 fractions had maximum EUD and TCP values at SD of around 5Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. The bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV is varies. The results suggest the potential for allowing some degree of dose heterogeneity within a CTV, although further investigations of the assumptions of the bystander model are warranted.« less

The prostate cancer screening clinic in the Bahamas: a model for low- and middle-income countries.

PubMed

Roberts, Robin; Mitchell, Corydon; Tancawan, Ana Lourdes; Pedican, Mandi; Jones, Glenn Wayne

2017-11-01

Grand Bahama (pop. 51,000) is an island within the Bahamas archipelago. A local chapter of International Us TOO Prostate Cancer Support Group (UTGB) has led an annual community-based prostate cancer screening clinic in Grand Bahama each September since 2009. Features of this initiative, characteristics of attendees, and a description of found cancers were summarized to determine the clinic's value and to guide improvements. We analyzed the established clinic from 2012 to 2015, wherein UTGB attracted corporate funding, volunteers managed clinics, and health professionals provided healthcare services. An explicit algorithm was used to sort clients by age, comorbidities, and findings from digital rectal examinations, and prostate-specific antigen (PSA) values, to determine which clients would undergo secondary assessment and prostate biopsy. Overall, 1,844 males were registered (mean age 57.6 years), and only 149 men attended on more than one occasion for a total of 1,993 clinic visit. The urologist reviewed 315 men in secondary follow-up, for elevated PSA and/or an abnormal digital rectal examination. Of these, 45 men fulfilled criteria for trans-rectal ultrasound biopsy, and there were 40 found cases of prostate cancer, for a positive-predictive value of 89%. By D'Amico risk-stratification, these 40 cases were low (10%), intermediate (40%), and high risk (50%). The urologist counseled all 40 cases and facilitated access to standard care. This study suggests that low-resource countries can advance cost-effective screening clinics, apply policy guidelines, and provide services within acceptable standards of care. It is the expectation, with a sustained effort and community participation over the ensuing years, that earlier disease presentation will occur and, consequently, a concomitant decrease in the disease-specific mortality.

Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories.

PubMed

Arthur, Rhonda; Møller, Henrik; Garmo, Hans; Holmberg, Lars; Stattin, Pår; Malmstrom, Håkan; Lambe, Mats; Hammar, Niklas; Walldius, Göran; Robinson, David; Jungner, Ingmar; Hemelrijck, Mieke Van

2016-06-01

Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA<4 μg/L, while those with glucose levels of 5.6-6.9 mmol/L had a greater odds of PSA>20 μg/L compared to PSA 4.0-9.9 μg/L. Hypertriglyceridemia was also positively associated with PSA>20 μg/L. Hyperglycemic men had a greater odds of intermediate- and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

The Role of Central Metabolism in Prostate Cancer Progression

DTIC Science & Technology

2012-07-01

AD_________________ Award Number: W81XWH-08-1-0694 TITLE: The Role of Central Metabolism in Prostate...SUBTITLE The Role of Central Metabolism in Prostate Cancer Progression 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-1-0694 5c. PROGRAM...examine the excised prostate tissue for differences in tumor growth, proteomes and intermediates in polyunsaturated fatty acid (PUFA) metabolism . The

Optimized color decomposition of localized whole slide images and convolutional neural network for intermediate prostate cancer classification

NASA Astrophysics Data System (ADS)

Zhou, Naiyun; Gao, Yi

2017-03-01

This paper presents a fully automatic approach to grade intermediate prostate malignancy with hematoxylin and eosin-stained whole slide images. Deep learning architectures such as convolutional neural networks have been utilized in the domain of histopathology for automated carcinoma detection and classification. However, few work show its power in discriminating intermediate Gleason patterns, due to sporadic distribution of prostate glands on stained surgical section samples. We propose optimized hematoxylin decomposition on localized images, followed by convolutional neural network to classify Gleason patterns 3+4 and 4+3 without handcrafted features or gland segmentation. Crucial glands morphology and structural relationship of nuclei are extracted twice in different color space by the multi-scale strategy to mimic pathologists' visual examination. Our novel classification scheme evaluated on 169 whole slide images yielded a 70.41% accuracy and corresponding area under the receiver operating characteristic curve of 0.7247.

Investigative clinical study on prostate cancer part III: exploring total PSA and free testosterone distributions and linear correlations in groups and subgroups of operated prostate cancer patients according to the total PSA/FT ratio.

PubMed

Porcaro, Antonio B; Petrozziello, Aldo; Romano, Mario; Sava, Teodoro; Ghimenton, Claudio; Caruso, Beatrice; Migliorini, Filippo; Zecchini Antoniolli, Stefano; Rubilotta, Emanuele; Lacola, Vincenzo; Monaco, Carmelo; Comunale, Luigi

2010-01-01

Prostate cancer is an interesting tumor for endocrine investigation. The prostate-specific antigen/free testosterone (PSA/FT) ratio has been shown to be effective in clustering patients in prognostic groups as follows: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40) and high risk (PSA/FT >0.40 and ≤1.5). In the present study we explored the total PSA and FT distributions, and linear regression of FT predicting PSA in the different groups (PSA/FT, pT and pG) and subgroups (pT and pG) of patients according to the prognostic PSA/FT ratio. The study included 128 operated prostate cancer patients. Pretreatment simultaneous serum samples were obtained for measuring free testosterone (FT) and total PSA levels. Patients were grouped according to the total PSA/FT ratio prognostic clusters (≤0.20, >0.20 and ≤0.40, >0.40), pT (2, 3a and 3b+4) and pathological Gleason score (pG) (≤6, = 7 >3 + 4, ≥7 >4 + 3). The pT and pG sets were subgrouped according to the prognostic PSA/FT ratio. Linear regression analysis of FT predicting total PSA was computed according to the different PSA/FT prognostic clusters for the: (1) total sample population, (2) pT and pG groups, (3) intraprostatic (pT2) and extraprostatic disease (pT3a/3b/4), and (4) low-intermediate grade (pG ≤6) and high-grade (pG ≥7) prostate cancer. Analysis of variance always showed highly significant different PSA distributions for (1) the different PSA/FT, pT and pG groups; and (2) the pT and pG prognostic subgroups. Significant FT distributions were detected for the (1) PSA/FT and pT groups; and (2) the pT2, pT3a and pG ≤6 prognostic PSA/FT subgroups. Correlation, variance and linear regression analysis of FT predicting total PSA was significant for (1) the PSA/FT prognostic clusters, (2) all the pT2 and pT3a subgroups, and (3) the pT3b/4 subgroup with PSA/FT >0.20 and ≤0.40, and (4) all the pG subsets. Linear regression analysis showed that the slopes of the predicting variable (FT) were always highly significant for patients with (1) intraprostate and extraprostate disease, and (2) low-grade and high-grade prostate cancer. According to the prognostic PSA/FT ratio, significantly lower levels of FT are detected in prostate cancer patients with extensive and high-grade disease. Also, significant linear correlations of FT predicting PSA are assessed in the different groups and subgroups of patients clustered according to the prognostic PSA/FT ratio. Confirmatory studies are needed. Copyright © 2010 S. Karger AG, Basel.

The role of CD133 in normal human prostate stem cells and malignant cancer-initiating cells.

PubMed

Vander Griend, Donald J; Karthaus, Wouter L; Dalrymple, Susan; Meeker, Alan; DeMarzo, Angelo M; Isaacs, John T

2008-12-01

Resolving the specific cell of origin for prostate cancer is critical to define rational targets for therapeutic intervention and requires the isolation and characterization of both normal human prostate stem cells and prostate cancer-initiating cells (CIC). Single epithelial cells from fresh normal human prostate tissue and prostate epithelial cell (PrEC) cultures derived from them were evaluated for the presence of subpopulations expressing stem cell markers and exhibiting stem-like growth characteristics. When epithelial cell suspensions containing cells expressing the stem cell marker CD133+ are inoculated in vivo, regeneration of stratified human prostate glands requires inductive prostate stromal cells. PrEC cultures contain a small subpopulation of CD133+ cells, and fluorescence-activated cell sorting-purified CD133+ PrECs self-renew and regenerate cell populations expressing markers of transit-amplifying cells (DeltaNp63), intermediate cells (prostate stem cell antigen), and neuroendocrine cells (CD56). Using a series of CD133 monoclonal antibodies, attachment and growth of CD133+ PrECs requires surface expression of full-length glycosylated CD133 protein. Within a series of androgen receptor-positive (AR+) human prostate cancer cell lines, CD133+ cells are present at a low frequency, self-renew, express AR, generate phenotypically heterogeneous progeny negative for CD133, and possess an unlimited proliferative capacity, consistent with CD133+ cells being CICs. Unlike normal adult prostate stem cells, prostate CICs are AR+ and do not require functional CD133. This suggests that (a) AR-expressing prostate CICs are derived from a malignantly transformed intermediate cell that acquires "stem-like activity" and not from a malignantly transformed normal stem cell and (b) AR signaling pathways are a therapeutic target for prostate CICs.

A systematic review of hypofractionation for primary management of prostate cancer.

PubMed

Koontz, Bridget F; Bossi, Alberto; Cozzarini, Cesare; Wiegel, Thomas; D'Amico, Anthony

2015-10-01

Technological advances in radiation therapy delivery have permitted the use of high-dose-per-fraction radiation therapy (RT) for early-stage prostate cancer (PCa). Level 1 evidence supporting the safety and efficacy of hypofractionated RT is evolving as this modality becomes more widely utilized and refined. To perform a systematic review of the current evidence on the safety and efficacy of hypofractionated RT for early-stage PCa and to provide in-context recommendations for current application of this technology. Embase, PubMed, and Scopus electronic databases were queried for English-language articles from January 1990 through June 2014. Prospective studies with a minimum of 50 patients were included. Separate consideration was made for studies involving moderate hypofractionation (doses of 2.5-4Gy per fraction) and extreme hypofractionation (5-10Gy in 4-7 fractions). Six relatively small superiority designed randomized trials of standard fractionation versus moderate hypofractionation in predominantly low- and intermediate-risk PCa have been published with follow-up ranging from 4 to 8 yr, noting similar biochemical control (5-yr freedom from biochemical failure in modern studies is >80% for low-risk and intermediate-risk patients) and late grade ≥2 genitourinary and gastrointestinal toxicities (between 2% and 20%). Noninferiority studies are pending. In prospective phase 2 studies, extreme hypofractionation has promising 2- to 5-yr biochemical control rates of >90% for low-risk patients. Results from a randomized trial are expected in 2015. Moderate hypofractionation has 5-yr data to date establishing safety compared with standard fractionation, but 10-yr outcomes and longer follow-up are needed to establish noninferiority for clinical effectiveness. Extreme hypofractionation is promising but as yet requires reporting of randomized data prior to application outside of a clinical protocol. Hypofractionation for prostate cancer delivers relatively high doses of radiation per treatment. Prospective studies support the safety of moderate hypofractionation, while extreme fractionation may have greater toxicity. Both show promising cancer control but long-term results of noninferiority studies of both methods are required before use in routine treatment outside of clinical protocols. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Emotional Distress Increases the Likelihood of Undergoing Surgery among Men with Localized Prostate Cancer.

PubMed

Orom, Heather; Underwood, Willie; Biddle, Caitlin

2017-02-01

We determined whether among men with clinically localized prostate cancer, particularly men with low risk disease, greater emotional distress increases the likelihood of undergoing surgery vs radiation or active surveillance. Participants were 1,531 patients recruited from 2 academic and 3 community facilities (nonHispanic white 83%, nonHispanic black 11% and Hispanic 6%; low risk 36%, intermediate risk 49% and high risk 15%; choice of active surveillance 24%, radiation 27% and surgery 48%). Emotional distress was assessed shortly after diagnosis and after men made a treatment decision with the Distress Thermometer. We used multinomial logistic regression with robust standard errors to test if emotional distress at either point predicted treatment choice in the sample as a whole and after stratifying by D'Amico risk score. In the sample as a whole the participants who were more emotionally distressed at diagnosis were more likely to choose surgery over active surveillance (RRR 1.07; 95% CI 1.01, 1.14; p=0.02). Men who were more distressed close to the time they made a treatment choice were more likely to have chosen surgery over active surveillance (RRR 1.16; 95% CI 1.09, 1.24; p <0.001) or surgery over radiation (RRR 1.12; 95% CI 1.05, 1.19; p=0.001). This pattern was also found in men with low risk disease. Emotional distress may motivate men with low risk prostate cancer to choose more aggressive treatment. Addressing emotional distress before and during treatment decision making may reduce a barrier to the uptake of active surveillance. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer.

PubMed

Rybicki, B A; Kryvenko, O N; Wang, Y; Jankowski, M; Trudeau, S; Chitale, D A; Gupta, N S; Rundle, A; Tang, D

2016-06-01

Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I-III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR)=0.47; 95% confidence interval (CI)=0.27-0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR=3.56; 95% CI=1.15-10.99). Moreover, PSA velocity (P=0.008) and frequency of PSA testing (P=0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR=2.97; 95% CI=1.40-6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR=1.91; 95% CI=1.09-3.35). In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing-suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection.

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer

PubMed Central

Rybicki, BA; Kryvenko, ON; Wang, Y; Jankowski, M; Trudeau, S; Chitale, DA; Gupta, NS; Rundle, A; Tang, D

2016-01-01

BACKGROUND Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. METHODS Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I–III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). RESULTS Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR) = 0.47; 95% confidence interval (CI) = 0.27–0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR = 3.56; 95% CI = 1.15–10.99). Moreover, PSA velocity (P = 0.008) and frequency of PSA testing (P = 0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR = 2.97; 95% CI = 1.40–6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR = 1.91; 95% CI = 1.09–3.35). CONCLUSIONS In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing—suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection. PMID:26620738

Radiobiologically optimized couch shift: A new localization paradigm using cone-beam CT for prostate radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Yimei, E-mail: yhuang2@hfhs.org; Gardner, Stephen J.; Wen, Ning

2015-10-15

Purpose: To present a novel positioning strategy which optimizes radiation delivery by utilizing radiobiological response knowledge and evaluate its use during prostate external beam radiotherapy. Methods: Five patients with low or intermediate risk prostate cancer were evaluated retrospectively in this IRB-approved study. For each patient, a VMAT plan with one 358° arc was generated on the planning CT (PCT) to deliver 78 Gy in 39 fractions. Five representative pretreatment cone beam CTs (CBCT) were selected for each patient. The CBCT images were registered to PCT by a human observer, which consisted of an initial automated registration with three degrees-of-freedom, followedmore » by manual adjustment for agreement at the prostate/rectal wall interface. To determine the optimal treatment position for each CBCT, a search was performed centering on the observer-matched position (OM-position) utilizing a score function based on radiobiological and dosimetric indices (EUD{sub prostate}, D99{sub prostate}, NTCP{sub rectum}, and NTCP{sub bladder}) for the prostate, rectum, and bladder. We termed the optimal treatment position the radiobiologically optimized couch shift position (ROCS-position). Results: The dosimetric indices, averaged over the five patients’ treatment plans, were (mean ± SD) 79.5 ± 0.3 Gy (EUD{sub prostate}), 78.2 ± 0.4 Gy (D99{sub prostate}), 11.1% ± 2.7% (NTCP{sub rectum}), and 46.9% ± 7.6% (NTCP{sub bladder}). The corresponding values from CBCT at the OM-positions were 79.5 ± 0.6 Gy (EUD{sub prostate}), 77.8 ± 0.7 Gy (D99{sub prostate}), 12.1% ± 5.6% (NTCP{sub rectum}), and 51.6% ± 15.2% (NTCP{sub bladder}), respectively. In comparison, from CBCT at the ROCS-positions, the dosimetric indices were 79.5 ± 0.6 Gy (EUD{sub prostate}), 77.3 ± 0.6 Gy (D99{sub prostate}), 8.0% ± 3.3% (NTCP{sub rectum}), and 46.9% ± 15.7% (NTCP{sub bladder}). Excessive NTCP{sub rectum} was observed on Patient 5 (19.5% ± 6.6%) corresponding to localization at OM-position, compared to the planned value of 11.7%. This was mitigated with radiobiologically optimized localization, resulting in a reduced NTCP{sub rectum} value of 11.3% ± 3.5%. Overall, the treatment position optimization resulted in similar target dose coverage with reduced risk to rectum. Conclusions: These encouraging results illustrate the potential advantage of applying radiobiologically optimized correction for online image-guided radiotherapy of prostate patients.« less

Competing-risks mortality after radiotherapy vs. observation for localized prostate cancer: a population-based study.

PubMed

Abdollah, Firas; Sun, Maxine; Schmitges, Jan; Thuret, Rodolphe; Tian, Zhe; Shariat, Shahrokh F; Briganti, Alberto; Jeldres, Claudio; Perrotte, Paul; Montorsi, Francesco; Karakiewicz, Pierre I

2012-09-01

Contemporary patients with localized prostate cancer (PCa) are more frequently treated with radiotherapy. However, there are limited data on the effect of this treatment on cancer-specific mortality (CSM). Our objective was to test the relationship between radiotherapy and survival in men with localized PCa and compare it with those treated with observation. A population-based cohort identified 68,797 men with cT1-T2 PCa treated with radiotherapy or observation between the years 1992 and 2005. Propensity-score matching was used to minimize potential bias related to treatment assignment. Competing-risks analyses tested the effect of treatment type (radiotherapy vs. observation) on CSM, after accounting to other-cause mortality. All analyses were carried out within PCa risk, baseline comorbidity status, and age groups. Radiotherapy was associated with more favorable 10-year CSM rates than observation in patients with high-risk PCa (8.8 vs. 14.4%, hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.50-0.68). Conversely, the beneficial effect of radiotherapy on CSM was not evident in patients with low-intermediate risk PCa (3.7 vs. 4.1%, HR: 0.91, 95% CI: 0.80-1.04). Radiotherapy was beneficial in elderly patients (5.6 vs. 7.3%, HR: 0.70, 95% CI: 0.59-0.80). Moreover, it was associated with improved CSM rates among patients with no comorbidities (5.7 vs. 6.5%, HR: 0.81, 95% CI: 0.67-0.98), one comorbidity (4.6 vs. 6.0%, HR: 0.87, 95% CI: 0.75-0.99), and more than two comorbidities (4.2 vs. 5.0%, HR: 0.79, 95% CI: 0.65-0.96). Radiotherapy substantially improves CSM in patients with high-risk PCa, with little or no benefit in patients with low-/intermediate-risk PCa relative to observation. These findings must be interpreted within the context of the limitations of observational data. Copyright © 2012 Elsevier Inc. All rights reserved.

Do Intermediate Radiation Doses Contribute to Late Rectal Toxicity? An Analysis of Data From Radiation Therapy Oncology Group Protocol 94-06

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tucker, Susan L., E-mail: sltucker@mdanderson.org; Dong, Lei; Michalski, Jeff M.

2012-10-01

Purpose: To investigate whether the volumes of rectum exposed to intermediate doses, from 30 to 50 Gy, contribute to the risk of Grade {>=}2 late rectal toxicity among patients with prostate cancer receiving radiotherapy. Methods and Materials: Data from 1009 patients treated on Radiation Therapy Oncology Group protocol 94-06 were analyzed using three approaches. First, the contribution of intermediate doses to a previously published fit of the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model was determined. Next, the extent to which intermediate doses provide additional risk information, after taking the LKB model into account, was investigated. Third, the proportionmore » of rectum receiving doses higher than a threshold, VDose, was computed for doses ranging from 5 to 85 Gy, and a multivariate Cox proportional hazards model was used to determine which of these parameters were significantly associated with time to Grade {>=}2 late rectal toxicity. Results: Doses <60 Gy had no detectable impact on the fit of the LKB model, as expected on the basis of the small estimate of the volume parameter (n = 0.077). Furthermore, there was no detectable difference in late rectal toxicity among cohorts with similar risk estimates from the LKB model but with different volumes of rectum exposed to intermediate doses. The multivariate Cox proportional hazards model selected V75 as the only value of VDose significantly associated with late rectal toxicity. Conclusions: There is no evidence from these data that intermediate doses influence the risk of Grade {>=}2 late rectal toxicity. Instead, the critical doses for this endpoint seem to be {>=}75 Gy. It is hypothesized that cases of Grade {>=}2 late rectal toxicity occurring among patients with V75 less than approximately 12% may be due to a 'background' level of risk, likely due mainly to biological factors.« less

Competing risk analysis of mortality in prostate cancer treated with radical prostatectomy.

PubMed

Ruiz-Cerdá, J L; Soto-Poveda, A; Luján-Marco, S; Loras-Monfort, A; Trassierra-Villa, M; Rogel-Bertó, R; Boronat-Tormo, F

To determine the risk of cancer-specific mortality (CSM) versus the competing risk of mortality by other causes (MOC) in patients with localised prostate cancer (LPC) treated with radical prostatectomy (RP). An observational cohort study of 982 patients with LPC treated with RP selected from our department's PC registry database. A competing risk analysis was performed, calculating the probability of CSM in the presence of the competing risk of MOC. Cumulative incidence curves were constructed, and point estimates were performed at 5, 10 and 15 years. The analysis was stratified by age (≤65 vs. >65 years) and risk group: low (Gleason score ≤6 and pT2abc); intermediate (Gleason score of 7 and pT2abc) and high (Gleason score of 8-10 or pT3ab). With a median follow-up of 60 months, the overall probability of dying from PC was 3.5%, and the probability of dying from other causes was 9%. A competing effect for MOC was observed. The risk of MOC was almost 3 times greater than that of CSM. This effect remained for all risk groups, although its magnitude decreased progressively according to the risk group level. At 10 years, CSM was only 0%, 1% and 2% for the low, intermediate and high-risk groups, respectively, while the likelihood of MOC was 4%, 4% and 10%, respectively. The mortality risk was shown after 10years of follow-up and was higher for other causes not attributable to PC and for patients older than 65years. The benefit of RP might be overestimated, given that the risk of MOC is greater than that of CSM, regardless of the age group and risk group, especially after 10years of follow-up. The only parameter that varied was the magnitude of the CSM/MOC ratio. This information could help in choosing the active treatment for patients with LPC and short life expectancies. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

A risk-adjusted definition of biochemical recurrence after radical prostatectomy.

PubMed

Morgan, T M; Meng, M V; Cooperberg, M R; Cowan, J E; Weinberg, V; Carroll, P R; Lin, D W

2014-06-01

To determine whether a variable definition of biochemical recurrence (BCR) based on clincopathologic features facilitates early identification of patients likely to suffer from disease progression. The definition of BCR after radical prostatectomy (RP) bears important implications for patient counseling and management; however, there remains a significant debate regarding the appropriate definition. The study cohort consisted of 3619 men who underwent RP for localized prostate cancer from 1989 to 2007, with data abstracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Patients were stratified into three risk groups according to Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score. Three single threshold PSA cut-points for BCR were evaluated (PSA > or =0.05, > or =0.2 and > or =0.4 ng ml(-1)) as well as a variable cut-point defined by risk group. After reaching the cut-points, patients were followed for further PSA progression. The proportion of patients with BCR differed by cut-point and risk group, ranging from 7 to 37% (low risk), 22 to 58% (intermediate risk) and 60 to 86% (high risk). The positive-predictive value (PPV) for predicting further PSA progression was 49% for the PSA > or =0.05 ng ml(-1), 62% for the PSA > or =0.2 ng ml(-1), 65% for the PSA > or =0.4 ng ml(-1) and 68% for the risk-adjusted definition. Five-year progression-free survival was 39% for the risk-adjusted definition compared with 45-52% for the other definitions of BCR. These data suggest that a variable definition of BCR determined by clinicopathologic risk may improve the identification of early recurrence after RP without increasing the overdiagnosis of BCR. By using a risk-adjusted BCR definition, clinicians can better predict future PSA progression and more appropriately counsel patients regarding salvage therapies.

Investigative clinical study on prostate cancer part IX and X: estradiol and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population after radical prostatectomy.

PubMed

Porcaro, Antonio B; Ghimenton, Claudio; Petrozziello, Aldo; Sava, Teodoro; Migliorini, Filippo; Romano, Mario; Caruso, Beatrice; Cocco, Claudio; Antoniolli, Stefano Zecchinini; Lacola, Vincenzo; Rubilotta, Emanuele; Monaco, Carmelo

2012-10-01

To evaluate estradiol (E(2)) physiopathology along the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer (PC) and subsequent cluster selection of the patient population. Records of the diagnosed (n=105) and operated (n=91) patients were retrospectively reviewed. Age, percentage of positive cores at-biopsy (P+), biopsy Gleason score (bGS), E(2), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), free-testosterone (FT), prostate-specific antigen (PSA), pathology Gleason score (pGS), estimated tumor volume in relation to percentage of prostate volume (V+), overall prostate weight (Wi), clinical stage (cT), biopsy Gleason pattern (bGP) and pathology stage (pT), were the investigated variables. None of the patients had previously undergone hormonal manipulations. E(2) correlation and prediction by multiple linear regression analysis (MLRA) was performed. At diagnosis, the log E(2)/log bGS ratio clustered the population into groups A (log E(2)/log bGS ≤ 2.25), B (2.25

Comparison between high-intensity focused ultrasound devices for the treatment of patients with localized prostate cancer

NASA Astrophysics Data System (ADS)

Kim, Hakushi; Tomonaga, Tetsuro; Shoji, Sunao; Uchida, Toyoaki

2017-03-01

To evaluate the association between long-term clinical outcomes and morbidity of patients with prostate cancer who underwent high-intensity focused ultrasound (HIFU). We included 918 patients with stage T1c-T3N0M0 prostate cancer who were treated with Sonablate™ (SB) devices during 1999-2012 and followed-up for >2 years. Risk stratification and complication rates were compared between the treatment groups. The 10-year overall and cancer-specific survival rates were 89.6% and 97.4%, respectively. The 5-year biochemical disease-free survival (bDFS) rates in the SB200/500, SB500 version 4, and SB500 tissue change monitor groups were 48.3%, 62.3%, and 82.0%, respectively (p < 0.0001). In the low-, intermediate-, and high-risk categories, the 10-year bDFS rates for all patients were 63%, 52%, and 32%, respectively (p < 0.0001), whereas the 5-year bDFS rates in the tissue change monitor group were 95%, 84%, and 72%, respectively (p = 0.0134). The overall negative biopsy rate was 87.3%. Multivariate analysis showed pre-treatment serum prostate-specific antigen levels, neoadjuvant hormonal therapy, and devices as significant predictors (p < 0.0001). Urethral stricture, epididymitis, and urinary incontinence were observed in 19.7%, 6.2%, and 2.3% of the cases, respectively. Long-term follow-up with HIFU demonstrated improved clinical outcomes owing to technical, imaging, and technological advancements.

Clinical significance of prospectively assigned Gleason tertiary pattern 4 in contemporary Gleason score 3+3=6 prostate cancer.

PubMed

Doshi, Chirag; Vacchio, Michael; Attwood, Kristopher; Murekeyisoni, Christine; Mehedint, Diana C; Badkhshan, Shervin; Azabdaftari, Gissou; Sule, Norbert; Guru, Khurshid A; Mohler, James L; Kauffman, Eric C

2016-06-01

To determine the oncologic impact of prospectively assigned tertiary pattern 4 in contemporary Gleason score (GS) 3 + 3 = 6 radical prostatectomy (RP) specimens. Oncologic outcomes were retrospectively reviewed for 720 consecutive patients from a single National Comprehensive Cancer Network (NCCN) center with at least 6 months follow-up after RP for GS3 + 3 = 6 (GS6, N = 222), GS6 with tertiary pattern 4 (GS6t4, N = 62), or GS3 + 4 = 7 (N = 436) prostate cancer, as prospectively graded since 2006 using the 2005 International Society of Urologic Pathologists criteria. Preoperative NCCN risk category, RP pathology, progression-free survival (PFS) and metastasis-free survival (MFS) were compared among the GS6, GS6t4, and GS3 + 4 = 7 groups using χ(2) , Kaplan-Meier, and log-rank analyses. The incidence of low NCCN preoperative risk classification for GS6t4 patients (63%) was less than that for GS6 patients (77%) while greater than that for GS3 + 4 = 7 patients (30%, P < 0.001). GS6t4 patients had RP pathologic features which were intermediate in risk between that of GS6 and GS3 + 4 = 7 based on extraprostatic extension (27% vs. 6% vs. 31%, respectively, P < 0.001) and mean percentage of prostate gland involvement (13% vs. 10% vs. 16%, respectively, P < 0.001). With a mean overall follow-up of 42 months, PFS for GS6t4 patients (5-year 85%) was intermediate between that of GS6 (5-year 93%) and GS3 + 4 = 7 (5-year 76%) patients (P < 0.001). The 5-year MFS rate was 100% for GS6 and GS6t4 patients compared to 97% for GS3 + 4 = 7 patients (P = 0.07). This study provides the longest follow-up to date for RP patients with prospectively assigned GS6t4 and supports a risk for adverse RP pathology and postoperative disease progression that is intermediate between GS6 and GS3 + 4 = 7. Whether a tertiary pattern 4 in GS6 disease increases the risk of metastasis is uncertain and requires longer term study. Given favorable oncologic outcomes, less stringent postoperative surveillance for both GS6 and GS6t4 patients may be warranted. © 2016 Wiley Periodicals, Inc.

Identification of men with low-risk biopsy-confirmed prostate cancer as candidates for active surveillance.

PubMed

Lin, Daniel W; Crawford, E David; Keane, Thomas; Evans, Brent; Reid, Julia; Rajamani, Saradha; Brown, Krystal; Gutin, Alexander; Tward, Jonathan; Scardino, Peter; Brawer, Michael; Stone, Steven; Cuzick, Jack

2018-06-01

A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS. The score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort. In the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 × 10 -5 ). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively). The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS. Copyright © 2018 Elsevier Inc. All rights reserved.

Prostate-Specific Antigen Halving Time While on Neoadjuvant Androgen Deprivation Therapy Is Associated With Biochemical Control in Men Treated With Radiation Therapy for Localized Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malik, Renuka; Jani, Ashesh B.; Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.ed

2011-03-15

Purpose: To assess whether the PSA response to neoadjuvant androgen deprivation therapy (ADT) is associated with biochemical control in men treated with radiation therapy (RT) for prostate cancer. Methods and Materials: In a cohort of men treated with curative-intent RT for localized prostate cancer between 1988 and 2005, 117 men had PSA values after the first and second months of neoadjuvant ADT. Most men had intermediate-risk (45%) or high-risk (44%) disease. PSA halving time (PSAHT) was calculated by first order kinetics. Median RT dose was 76 Gy and median total duration of ADT was 4 months. Freedom from biochemical failuremore » (FFBF, nadir + 2 definition) was analyzed by PSAHT and absolute PSA nadir before the start of RT. Results: Median follow-up was 45 months. Four-year FFBF was 89%. Median PSAHT was 2 weeks. A faster PSA decline (PSAHT {<=}2 weeks) was associated with greater FFBF (96% vs. 81% for a PSAHT >2 weeks, p = 0.0110). Those within the fastest quartile of PSAHTs ({<=} 10 days) achieved a FFBF of 100%. Among high-risk patients, a PSAHT {<=}2 weeks achieved a 4-yr FFBF of 93% vs. 70% for those with PSAHT >2 weeks (p = 0.0508). Absolute PSA nadir was not associated with FFBF. On multivariable analysis, PSAHT (p = 0.0093) and Gleason score (p = 0.0320) were associated with FFBF, whereas T-stage (p = 0.7363) and initial PSA level (p = 0.9614) were not. Conclusions: For men treated with combined ADT and RT, PSA response to the first month of ADT may be a useful criterion for prognosis and treatment modification.« less

Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations.

PubMed

Häggström, Christel; Stocks, Tanja; Nagel, Gabriele; Manjer, Jonas; Bjørge, Tone; Hallmans, Göran; Engeland, Anders; Ulmer, Hanno; Lindkvist, Björn; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär

2014-11-01

Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes. In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, cholesterol, and triglycerides were collected from 285,040 men. Risks of prostate cancer diagnosis, prostate cancer death, and death from other causes were calculated by use of competing risk analysis for men with normal (bottom 84%) and high (top 16%) levels of each factor, and a composite score. During a mean follow-up period of 12 years, 5,893 men were diagnosed with prostate cancer, 1,013 died of prostate cancer, and 26,328 died of other causes. After 1996, when prostate-specific antigen testing was introduced, men up to age 80 years with normal metabolic levels had 13% risk of prostate cancer, 2% risk of prostate cancer death, and 30% risk of death from other causes, whereas men with metabolic aberrations had corresponding risks of 11%, 2%, and 44%. In contrast to recent studies using conventional survival analysis, in a real-world scenario taking risk of competing events into account, men with metabolic aberrations had lower risk of prostate cancer diagnosis, similar risk of prostate cancer death, and substantially higher risk of death from other causes compared with men who had normal metabolic levels.

Evaluation of the Prostate Cancer Prevention Trial Risk Calculator in a High-Risk Screening Population

PubMed Central

Kaplan, David J.; Boorjian, Stephen A.; Ruth, Karen; Egleston, Brian L.; Chen, David Y.T.; Viterbo, Rosalia; Uzzo, Robert G.; Buyyounouski, Mark K.; Raysor, Susan; Giri, Veda N.

2009-01-01

Introduction Clinical factors in addition to PSA have been evaluated to improve risk assessment for prostate cancer. The Prostate Cancer Prevention Trial (PCPT) risk calculator provides an assessment of prostate cancer risk based on age, PSA, race, prior biopsy, and family history. This study evaluated the risk calculator in a screening cohort of young, racially diverse, high-risk men with a low baseline PSA enrolled in the Prostate Cancer Risk Assessment Program. Patients and Methods Eligibility for PRAP include men ages 35-69 who are African-American, have a family history of prostate cancer, or have a known BRCA1/2 mutation. PCPT risk scores were determined for PRAP participants, and were compared to observed prostate cancer rates. Results 624 participants were evaluated, including 382 (61.2%) African-American men and 375 (60%) men with a family history of prostate cancer. Median age was 49.0 years (range 34.0-69.0), and median PSA was 0.9 (range 0.1-27.2). PCPT risk score correlated with prostate cancer diagnosis, as the median baseline risk score in patients diagnosed with prostate cancer was 31.3%, versus 14.2% in patients not diagnosed with prostate cancer (p<0.0001). The PCPT calculator similarly stratified the risk of diagnosis of Gleason score ≥7 disease, as the median risk score was 36.2% in patients diagnosed with Gleason ≥7 prostate cancer versus 15.2% in all other participants (p<0.0001). Conclusion PCPT risk calculator score was found to stratify prostate cancer risk in a cohort of young, primarily African-American men with a low baseline PSA. These results support further evaluation of this predictive tool for prostate cancer risk assessment in high-risk men. PMID:19709072

Expanding indication of padeliporfin (WST11) vascular-targeted photodynamic therapy: results of prostate cancer Latin-American multicenter study.

PubMed

Rodriguez-Rivera, J A; Rodriguez-Lay, R; Zegarra-Montes, L; Benzaghou, F; Gaillac, B; Azzouzi, A R; Reis, L O; Palma, P

2018-04-23

To explore the proportion of patients with higher risk localized prostate cancer (PCa) that would become safely biopsy negative 12 months after non-thermal focal therapy with padeliporfin vascular-targeted photodynamic therapy (VTP). Multicenter study in a scenario of prostate-specific antigen (PSA) ≤20ng/ml and variable PCa target volumes Gleason pattern 3 or low-volume secondary Gleason pattern 4, all patients received VTP, consisting of intravenous 4mg/kg padeliporfin activated by light-diffusing fibers in the prostate. The prostate was biopsied at baseline, months 6 and 12, PSA, patient-reported functional outcomes and quality of life (QoL) questionnaires were recorded at baseline, months 3, 6, and 12 and adverse events (AE) throughout the study. In the intention-to-treat population (n=81), the proportion of patients with negative biopsies at month 12 was 74% (60/81 patients; 95% CI: 63.1%,83.2%). In the per-protocol population, the proportion was 79% (58/73 patients; 95% CI: 68.4%,88.0%). Questionnaire results indicated a slight improvement in urinary function and limited deterioration in sexual function. No difference in QoL was observed over time. A total of 42/81 (52%) patients reported mild or moderate and 4 of 81 (4.9%) experienced serious AE, all resolved without sequelae. No phototoxicity, cardiovascular event, fistula or prolonged urinary incontinence, secondary cancer or death was reported. Results support the efficacy, safety, and QoL associated with padeliporfin focal treatment for low/intermediate risk localized PCa. Copyright © 2018 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Multiparametric Magnetic-Resonance to Confirm Eligibility to an Active Surveillance Program for Low-Risk Prostate Cancer: Intermediate Time Results of a Third Referral High Volume Centre Active Surveillance Protocol.

PubMed

Luzzago, Stefano; Musi, Gennaro; Catellani, Michele; Russo, Andrea; Di Trapani, Ettore; Mistretta, Francesco Alessandro; Bianchi, Roberto; Cozzi, Gabriele; Conti, Andrea; Pricolo, Paola; Ferro, Matteo; Matei, Deliu-Victor; Mirone, Vincenzo; Petralia, Giuseppe; de Cobelli, Ottavio

2018-05-07

To evaluate the role of confirmatory multiparametric magnetic resonance imaging (mpMRI) of the prostate at the time of Active Surveillance (AS) enrollment to reduce disease misclassification. From 2012 to 2016, 383 patients with low-risk disease respecting Prostate Cancer Research International AS criteria underwent confirmatory 1.5-T mpMRI. AS was proposed to patients with Prostate Imaging and Report and Data System (PI-RADS) score ≤3 and no extraprostatic extension (EPE), whereas patients with PI-RADS score ≥4 and/or EPE were treated actively. Kaplan-Meier analyses quantified progression-free survival (PFS) in patients enrolled in the AS program. Logistic regression analyses tested the association between confirmatory mpMRI and clinically significant prostate cancer (csPCa) at radical prostatectomy (RP). Diagnostic performance of mpMRI was calculated in patients submitted to immediate RP. PFS rate was 99, 90 and 86% at 1, 2 and 3 years respectively. At multivariable analysis, PI-RADS 3, PI-RADS 4, PI-RADS 5 and EPE increased the probability of having csPCa at immediate RP (PI-RADS 3 [OR] 1.2, p = 0.26; PI-RADS 4 [OR] 5.1, p = 0.02; PI-RADS 5 [OR] 6.7; p = 0.009; EPE [OR] 11.8, p < 0.001). Confirmatory mpMRI showed sensibility, specificity, positive predictive value and negative predictive value of 85, 55, 68 and 76% respectively. MpMRI at the time of AS enrollment reduces the misclassification rate of csPCa. We suggest to perform target biopsies in patients with PI-RADS score 3 and 4 lesions. © 2018 S. Karger AG, Basel.

Upgrading the Gleason Score in Extended Prostate Biopsy: Implications for Treatment Choice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moreira Leite, Katia Ramos; Laboratory of Surgical and Molecular Pathology - Hospital Sirio Libanes, Sao Paulo; Camara-Lopes, Luiz H.A.

2009-02-01

Purpose: To determine the incidence of overestimation of Gleason score (GS) in extended prostate biopsy, and consequently circumventing unnecessary aggressive treatment. Methods and Materials: This is a retrospective study of 464 patients who underwent prostate biopsy and radical prostatectomy between January 2001 and November 2007. The GS from biopsy and radical prostatectomy were compared. The incidence of overestimation of GS in biopsies and tumor volume were studied. Multivariate analysis was applied to find parameters that predict upgrading the GS in prostate biopsy. Results: The exact agreement of GS between prostate biopsy and radical prostatectomy occurred in 56.9% of cases. Inmore » 29.1% cases it was underestimated, and it was overestimated in 14%. One hundred and six (22.8%) patients received a diagnosis of high GS (8, 9, or 10) in a prostate biopsy. In 29.2% of cases, the definitive Gleason Score was 7 or lower. In cases in which GS was overestimated in the biopsy, tumors were significantly smaller. In multivariate analysis, the total percentage of tumor was the only independent factor in overestimation of GS. Tumors occupying less than 33% of cores had a 5.6-fold greater chance of being overestimated. Conclusion: In the extended biopsy era and after the International Society of Urological Pathology consensus on GS, almost one third of tumors considered to have high GS at the biopsy may be intermediate-risk cancers. In that condition, tumors are smaller in biopsy. This should be remembered by professionals involved with prostate cancer to avoid overtreatment and undesirable side effects.« less

Dosimetric and geometric evaluation of a hybrid strategy of offline adaptive planning and online image guidance for prostate cancer radiotherapy

PubMed Central

Liu, Han; Wu, Qiuwen

2011-01-01

For prostate cancer patients, online image-guided (IG) radiotherapy has been widely used in clinic to correct the translational inter-fractional motion at each treatment fraction. For uncertainties that cannot be corrected online, such as rotation and deformation of the target volume, margins are still required to be added to the clinical target volume (CTV) for the treatment planning. Offline adaptive radiotherapy has been implemented to optimize the treatment for each individual patient based on the measurements at early stages of treatment process. It has been shown that offline adaptive radiotherapy can effectively reduce the required margin. Recently a hybrid strategy of offline adaptive replanning and online IG was proposed and the geometric evaluation was performed. It was found that the planning margins can be further reduced by 1–2 mm compared to online IG only strategy. The purpose of this study was to investigate the dosimetric benefits of such hybrid strategy on the target and organs at risk (OARs). A total of 420 repeated helical computed tomography (HCT) scans from 28 patients were included in the study. Both low-risk patients (LRP, CTV = prostate) and intermediate-risk patients (IRP, CTV = prostate + seminal vesicles, SV) were included in the simulation. Two registration methods, based on center-of-mass (COM) shift of prostate only and prostate plus SV, were performed for IRP. The intensity modulated radiotherapy (IMRT) was used in the simulation. Criteria on both cumulative dose and fractional doses were evaluated. Furthermore, the geometric evaluation was extended to investigate the optimal number of fractions necessary to construct the internal target volume (ITV) for the hybrid strategy. The dosimetric margin improvement was smaller than its geometric counterpart and was in the range of 0 mm to 1 mm. The optimal number of fractions necessary for the ITV construction is 2 for LRP and 3–4 for IRP in a hypofractionation protocol. A new cumulative index of target volume (CITV) was proposed for the evaluation of adaptive radiotherapy strategies, and it was found that it had the advantages over other indices in evaluating different adaptive radiotherapy strategies. PMID:21772083

Dosimetric and geometric evaluation of a hybrid strategy of offline adaptive planning and online image guidance for prostate cancer radiotherapy.

PubMed

Liu, Han; Wu, Qiuwen

2011-08-07

For prostate cancer patients, online image-guided (IG) radiotherapy has been widely used in clinic to correct the translational inter-fractional motion at each treatment fraction. For uncertainties that cannot be corrected online, such as rotation and deformation of the target volume, margins are still required to be added to the clinical target volume (CTV) for the treatment planning. Offline adaptive radiotherapy has been implemented to optimize the treatment for each individual patient based on the measurements at early stages of treatment process. It has been shown that offline adaptive radiotherapy can effectively reduce the required margin. Recently a hybrid strategy of offline adaptive replanning and online IG was proposed and the geometric evaluation was performed. It was found that the planning margins can further be reduced by 1-2 mm compared to online IG only strategy. The purpose of this study was to investigate the dosimetric benefits of such a hybrid strategy on the target and organs at risk. A total of 420 repeated helical computed tomography scans from 28 patients were included in the study. Both low-risk patients (LRP, CTV = prostate) and intermediate-risk patients (IRP, CTV = prostate + seminal vesicles, SV) were included in the simulation. Two registration methods, based on center-of-mass shift of prostate only and prostate plus SV, were performed for IRP. The intensity-modulated radiotherapy was used in the simulation. Criteria on both cumulative and fractional doses were evaluated. Furthermore, the geometric evaluation was extended to investigate the optimal number of fractions necessary to construct the internal target volume (ITV) for the hybrid strategy. The dosimetric margin improvement was smaller than its geometric counterpart and was in the range of 0-1 mm. The optimal number of fractions necessary for the ITV construction is 2 for LRPs and 3-4 for IRPs in a hypofractionation protocol. A new cumulative index of target volume was proposed for the evaluation of adaptive radiotherapy strategies, and it was found that it had the advantages over other indices in evaluating different adaptive radiotherapy strategies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moteabbed, Maryam, E-mail: mmoteabbed@partners.org; Trofimov, Alexei; Sharp, Gregory C.

Purpose: To quantify and compare the impact of interfractional setup and anatomic variations on proton therapy (PT) and intensity modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Twenty patients with low-risk or intermediate-risk prostate cancer randomized to receive passive-scattering PT (n=10) and IMRT (n=10) were selected. For both modalities, clinical treatment plans included 50.4 Gy(RBE) to prostate and proximal seminal vesicles, and prostate-only boost to 79.2 Gy(RBE) in 1.8 Gy(RBE) per fraction. Implanted fiducials were used for prostate localization and endorectal balloons were used for immobilization. Patients in PT and IMRT arms received weekly computed tomography (CT) and cone beam CTmore » (CBCT) scans, respectively. The planned dose was recalculated on each weekly image, scaled, and mapped onto the planning CT using deformable registration. The resulting accumulated dose distribution over the entire treatment course was compared with the planned dose using dose-volume histogram (DVH) and γ analysis. Results: The target conformity index remained acceptable after accumulation. The largest decrease in the average prostate D{sub 98} was 2.2 and 0.7 Gy for PT and IMRT, respectively. On average, the mean dose to bladder increased by 3.26 ± 7.51 Gy and 1.97 ± 6.84 Gy for PT and IMRT, respectively. These values were 0.74 ± 2.37 and 0.56 ± 1.90 for rectum. Differences between changes in DVH indices were not statistically significant between modalities. All volume indices remained within the protocol tolerances after accumulation. The average pass rate for the γ analysis, assuming tolerances of 3 mm and 3%, for clinical target volume, bladder, rectum, and whole patient for PT/IMRT were 100/100, 92.6/99, 99.2/100, and 97.2/99.4, respectively. Conclusion: The differences in target coverage and organs at risk dose deviations for PT and IMRT were not statistically significant under the guidelines of this protocol.« less

End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer

PubMed Central

Narang, Amol K.; Trieu, Janson; Radwan, Noura; Ram, Ashwin; Robertson, Scott P.; He, Pei; Gergis, Carol; Griffith, Emily; Singh, Harleen; DeWeese, Tate A.; Honig, Stephanie; Annadanam, Anvesh; Greco, Stephen; DeVille, Curtiland; McNutt, Todd; DeWeese, Theodore L.; Song, Daniel Y.; Tran, Phuoc T.

2016-01-01

Background In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. Methods Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993–2006 and who had an EOR PSA (n=688, median follow-up 11.2 years). We analyzed the association of an end-of-radiation (EOR) prostate-specific antigen (PSA) level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ≥0.1 ng ml−1) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. Results At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% vs. 64.4%, p<0.001), 10-year MFS (84.8% vs. 92.0%, p=0.003), 10-year PCSS (94.3% vs. 98.2%, p=0.007), and 10-year OS (75.8% vs. 82.5%, p=0.01), as compared to men with an undetectable EOR PSA. Among NCCN intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37–14.65, p<0.001; NCCN risk level: HR 2.01, 95% CI 0.74–5.42, p=0.168). Main study limitations are retrospective study design and associated biases. Conclusions EOR PSA was significantly associated with survival endpoints in men who received treated with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation. PMID:28094250

Time to PSA rise differentiates the PSA bounce after HDR and LDR brachytherapy of prostate cancer

PubMed Central

Skowronek, Janusz

2018-01-01

Purpose To investigate the differences in prostate-specific antigen (PSA) bounce (PB) after high-dose-rate (HDR-BT) or low-dose-rate (LDR-BT) brachytherapy alone in prostate cancer patients. Materials and methods Ninety-four patients with localized prostate cancer (T1-T2cN0), age ranged 50-81 years, were treated with brachytherapy alone between 2008 and 2010. Patients were diagnosed with adenocarcinoma, Gleason score ≤ 7. The LDR-BT total dose was 144-145 Gy, in HDR-BT – 3 fractions of 10.5 or 15 Gy. The initial PSA level (iPSA) was assessed before treatment, then PSA was rated every 3 months over the first 2 years, and every 6 months during the next 3 years. Median follow-up was 3.0 years. Results Mean iPSA was 7.8 ng/ml. In 58 cases, PSA decreased gradually without PB or biochemical failure (BF). In 24% of patients, PB was observed. In 23 cases (24%), PB was observed using 0.2 ng/ml definition; in 10 cases (11%), BF was diagnosed using nadir + 2 ng/ml definition. The HDR-BT and LDR-BT techniques were not associated with higher level of PB (26 vs. 22%, p = 0.497). Time to the first PSA rise finished with PB was significantly shorter after HDR-BT then after LDR-BT (median, 10.5 vs. 18.0 months) during follow-up. Predictors for PB were observed only after HDR-BT. Androgen deprivation therapy (ADT) and higher Gleason score decreased the risk of PB (HR = 0.11, p = 0.03; HR = 0.51, p = 0.01). The higher PSA nadir and longer time to PSA nadir increased the risk of PB (HR 3.46, p = 0.02; HR 1.04, p = 0.04). There was no predictors for PB after LDR-BT. Conclusions HDR-BT and LDR-BT for low and intermediate risk prostate cancer had similar PB rate. The PB occurred earlier after HDR-BT than after LDR-BT. ADT and higher Gleason score decreased, and higher PSA nadir and longer time to PSA nadir increased the risk of PB after HDR-BT. PMID:29619050

Time to PSA rise differentiates the PSA bounce after HDR and LDR brachytherapy of prostate cancer.

PubMed

Burchardt, Wojciech; Skowronek, Janusz

2018-02-01

To investigate the differences in prostate-specific antigen (PSA) bounce (PB) after high-dose-rate (HDR-BT) or low-dose-rate (LDR-BT) brachytherapy alone in prostate cancer patients. Ninety-four patients with localized prostate cancer (T1-T2cN0), age ranged 50-81 years, were treated with brachytherapy alone between 2008 and 2010. Patients were diagnosed with adenocarcinoma, Gleason score ≤ 7. The LDR-BT total dose was 144-145 Gy, in HDR-BT - 3 fractions of 10.5 or 15 Gy. The initial PSA level (iPSA) was assessed before treatment, then PSA was rated every 3 months over the first 2 years, and every 6 months during the next 3 years. Median follow-up was 3.0 years. Mean iPSA was 7.8 ng/ml. In 58 cases, PSA decreased gradually without PB or biochemical failure (BF). In 24% of patients, PB was observed. In 23 cases (24%), PB was observed using 0.2 ng/ml definition; in 10 cases (11%), BF was diagnosed using nadir + 2 ng/ml definition. The HDR-BT and LDR-BT techniques were not associated with higher level of PB (26 vs. 22%, p = 0.497). Time to the first PSA rise finished with PB was significantly shorter after HDR-BT then after LDR-BT (median, 10.5 vs. 18.0 months) during follow-up. Predictors for PB were observed only after HDR-BT. Androgen deprivation therapy (ADT) and higher Gleason score decreased the risk of PB (HR = 0.11, p = 0.03; HR = 0.51, p = 0.01). The higher PSA nadir and longer time to PSA nadir increased the risk of PB (HR 3.46, p = 0.02; HR 1.04, p = 0.04). There was no predictors for PB after LDR-BT. HDR-BT and LDR-BT for low and intermediate risk prostate cancer had similar PB rate. The PB occurred earlier after HDR-BT than after LDR-BT. ADT and higher Gleason score decreased, and higher PSA nadir and longer time to PSA nadir increased the risk of PB after HDR-BT.

Lifestyle determinants of 5alpha-reductase metabolites in older African-American, white, and Asian-American men.

PubMed

Wu, A H; Whittemore, A S; Kolonel, L N; Stanczyk, F Z; John, E M; Gallagher, R P; West, D W

2001-05-01

Men with higher endogenous 5alpha-reductase activity may have higher prostate cancer risk. This hypothesis raises two questions: (a) Could racial differences in 5alpha-reductase activity explain the observed racial differences in prostate cancer risk? and (b) Could a man reduce his activity level by modifying his lifestyle? To address these questions, we measured two hormonal indices of 5alpha-reductase activity [serum levels of androstane-3alpha-17beta-diol glucuronide (3alpha-diol G) and androsterone glucuronide (AG)] in healthy, older African-American, white, and Asian-American men, who are at high, intermediate, and low prostate cancer risk, respectively. We also examined associations between these metabolite levels and such lifestyle characteristics as body size and physical activity as well as select aspects of medical history and family history of prostate cancer. Men included in this cross-sectional analysis (n = 1054) had served as control subjects in a population-based case-control study of prostate cancer we conducted in California, Hawaii, and Vancouver, Canada and provided information on certain personal attributes and donated blood between March 1990 and March 1992. In this study, concentrations of 3alpha-diol G declined significantly with age and increased significantly with body mass index. Mean levels of 3alpha-diol G, adjusted for age and body mass index, were 6.1 ng/ml in African-Americans, 6.9 ng/ml in whites and 4.8 ng/ml in Asian-Americans. These differences were statistically significant (African-Americans versus whites: P < 0.01; whites versus Asian-Americans: P < 0.001). Concentrations of AG decreased significantly with age, but only in whites, and were unrelated to any of the reported personal attributes. Mean levels of AG, adjusted for age, were 44.1 ng/ml in African-Americans, 44.9 ng/ml in whites, and 37.5 ng/ml in Asian-Americans (Asian-Americans versus whites, P < 0.001). In conclusion, older African-American and white men have similar levels of these two indices of 5alpha-reductase activity, and these levels are higher than those of older Asian-American men. This difference may be related to the lower prostate cancer risk in Asian-Americans.

Sentinel node biopsy for prostate cancer: report from a consensus panel meeting.

PubMed

van der Poel, Henk G; Wit, Esther M; Acar, Cenk; van den Berg, Nynke S; van Leeuwen, Fijs W B; Valdes Olmos, Renato A; Winter, Alexander; Wawroschek, Friedhelm; Liedberg, Fredrik; Maclennan, Steven; Lam, Thomas

2017-08-01

To explore the evidence and knowledge gaps in sentinel node biopsy (SNB) in prostate cancer through a consensus panel of experts. A two-round Delphi survey among experts was followed by a consensus panel meeting of 16 experts in February 2016. Agreement voting was performed using the research and development project/University of California, Los Angeles Appropriateness Methodology on 150 statements in nine domains. The disagreement index based on the interpercentile range, adjusted for symmetry score, was used to assess consensus and non-consensus among panel members. Consensus was obtained on 91 of 150 statements (61%). The main outcomes were: (1) the results from an extended lymph node dissection (eLND) are still considered the 'gold standard', and sentinel node (SN) detection should be combined with eLND, at least in patients with intermediate- and high-risk prostate cancer; (2) the role of SN detection in low-risk prostate cancer is unclear; and (3) future studies should contain oncological endpoints as number of positive nodes outside the eLND template, false-negative and false-positive SN procedures, and recurrence-free survival. A high rate of consensus was obtained regarding outcome measures of future clinical trials on SNB (89%). Consensus on tracer technology was only obtained in 47% of statements, reflecting a need for further research and standardization in this area. The low-level evidence in the available literature and the composition of mainly SNB users in the panel constitute the major limitations of the study. Consensus on a majority of elementary statements on SN detection in prostate cancer was obtained.; therefore, the results from this consensus report will provide a basis for the design of further studies in the field. A group of experts identified evidence and knowledge gaps on SN detection in prostate cancer and its application in daily practice. Information from the consensus statements can be used to direct further studies. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Association Between Travel Distance and Choice of Treatment for Prostate Cancer: Does Geography Reduce Patient Choice?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muralidhar, Vinayak, E-mail: vmuralidhar@partners.org; Rose, Brent S.; Chen, Yu-Wei

Objective: To determine whether the distance between a prostate cancer patient's home and treatment facility was related to the choice of treatment received among those opting for surgery or radiation. Methods and Materials: We identified 222,804 patients diagnosed with National Comprehensive Cancer Network low-, intermediate-, or high-risk N0M0 prostate cancer and treated with local therapy (surgery or radiation alone, with or without hormone therapy) using the National Cancer Database. We used multivariable logistic regression to determine whether the choice of radiation therapy vs radical prostatectomy varied by distance among patients living in rural and urban areas. Analyses were adjusted formore » geographic location within the United States, age, race, Charlson/Deyo comorbidity score, year of diagnosis, income quartile, education quartile, Gleason score, prostate-specific antigen level, and T stage. Results: Patients living in urban or rural areas were less likely to receive radiation compared with surgery if they lived farther from the treatment facility. Among urban patients living ≤5 miles from the treatment facility, 53.3% received radiation, compared with 47.0%, 43.6%, and 33.8% of those living 5 to 10, 10 to 15, or >15 miles away, respectively (P<.001 in all cases). Similarly, rural patients were less likely to receive radiation the farther they lived from the treatment facility (≤25 miles: 62.3%; 25-50 miles: 55.5%; 50-75 miles: 38.4%; >75 miles: 23.8%; P<.05 in all cases). These trends were also present when each risk group was analyzed separately. Conclusion: Patients with prostate cancer in both urban and rural settings were less likely to receive radiation therapy rather than surgery the farther away they lived from a treatment center. These findings raise the possibility that the geographic availability of radiation treatment centers may be an important determinant of whether patients are able to choose radiation rather than surgery for localized prostate cancer.« less

Logistic regression model for diagnosis of transition zone prostate cancer on multi-parametric MRI.

PubMed

Dikaios, Nikolaos; Alkalbani, Jokha; Sidhu, Harbir Singh; Fujiwara, Taiki; Abd-Alazeez, Mohamed; Kirkham, Alex; Allen, Clare; Ahmed, Hashim; Emberton, Mark; Freeman, Alex; Halligan, Steve; Taylor, Stuart; Atkinson, David; Punwani, Shonit

2015-02-01

We aimed to develop logistic regression (LR) models for classifying prostate cancer within the transition zone on multi-parametric magnetic resonance imaging (mp-MRI). One hundred and fifty-five patients (training cohort, 70 patients; temporal validation cohort, 85 patients) underwent mp-MRI and transperineal-template-prostate-mapping (TPM) biopsy. Positive cores were classified by cancer definitions: (1) any-cancer; (2) definition-1 [≥Gleason 4 + 3 or ≥ 6 mm cancer core length (CCL)] [high risk significant]; and (3) definition-2 (≥Gleason 3 + 4 or ≥ 4 mm CCL) cancer [intermediate-high risk significant]. For each, logistic-regression mp-MRI models were derived from the training cohort and validated internally and with the temporal cohort. Sensitivity/specificity and the area under the receiver operating characteristic (ROC-AUC) curve were calculated. LR model performance was compared to radiologists' performance. Twenty-eight of 70 patients from the training cohort, and 25/85 patients from the temporal validation cohort had significant cancer on TPM. The ROC-AUC of the LR model for classification of cancer was 0.73/0.67 at internal/temporal validation. The radiologist A/B ROC-AUC was 0.65/0.74 (temporal cohort). For patients scored by radiologists as Prostate Imaging Reporting and Data System (Pi-RADS) score 3, sensitivity/specificity of radiologist A 'best guess' and LR model was 0.14/0.54 and 0.71/0.61, respectively; and radiologist B 'best guess' and LR model was 0.40/0.34 and 0.50/0.76, respectively. LR models can improve classification of Pi-RADS score 3 lesions similar to experienced radiologists. • MRI helps find prostate cancer in the anterior of the gland • Logistic regression models based on mp-MRI can classify prostate cancer • Computers can help confirm cancer in areas doctors are uncertain about.

Association Between Travel Distance and Choice of Treatment for Prostate Cancer: Does Geography Reduce Patient Choice?

PubMed

Muralidhar, Vinayak; Rose, Brent S; Chen, Yu-Wei; Nezolosky, Michelle D; Nguyen, Paul L

2016-10-01

To determine whether the distance between a prostate cancer patient's home and treatment facility was related to the choice of treatment received among those opting for surgery or radiation. We identified 222,804 patients diagnosed with National Comprehensive Cancer Network low-, intermediate-, or high-risk N0M0 prostate cancer and treated with local therapy (surgery or radiation alone, with or without hormone therapy) using the National Cancer Database. We used multivariable logistic regression to determine whether the choice of radiation therapy vs radical prostatectomy varied by distance among patients living in rural and urban areas. Analyses were adjusted for geographic location within the United States, age, race, Charlson/Deyo comorbidity score, year of diagnosis, income quartile, education quartile, Gleason score, prostate-specific antigen level, and T stage. Patients living in urban or rural areas were less likely to receive radiation compared with surgery if they lived farther from the treatment facility. Among urban patients living ≤5 miles from the treatment facility, 53.3% received radiation, compared with 47.0%, 43.6%, and 33.8% of those living 5 to 10, 10 to 15, or >15 miles away, respectively (P<.001 in all cases). Similarly, rural patients were less likely to receive radiation the farther they lived from the treatment facility (≤25 miles: 62.3%; 25-50 miles: 55.5%; 50-75 miles: 38.4%; >75 miles: 23.8%; P<.05 in all cases). These trends were also present when each risk group was analyzed separately. Patients with prostate cancer in both urban and rural settings were less likely to receive radiation therapy rather than surgery the farther away they lived from a treatment center. These findings raise the possibility that the geographic availability of radiation treatment centers may be an important determinant of whether patients are able to choose radiation rather than surgery for localized prostate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Investigative clinical study on prostate cancer part II: on the role of the pretreatment total PSA to free testosterone ratio as a marker assessing prostate cancer prognostic groups after radical retropubic prostatectomy.

PubMed

Porcaro, Antonio B; Monaco, Carmelo; Romano, Mario; Petrozziello, Aldo; Rubilotta, Emanuele; Lacola, Vincenzo; Sava, Teodoro; Ghimenton, Claudio; Caruso, Beatrice; Antoniolli, Stefano Zecchini; Migliorini, Filippo; Comunale, Luigi

2010-01-01

To explore the significance of the pretreatment total prostate-specific antigen (PSA) to free testosterone (FT) ratio (PSA/FT) as a marker for assessing the pathologic Gleason sum (pGS) and levels of tumor extension (pT) in prostatectomy specimens. 128 of 135 consecutive patients diagnosed with prostate cancer underwent radical prostatectomy. Simultaneous pretreatment serum samples were obtained to measure serum total testosterone, FT and total PSA levels. The statistical design of the study included 2 sections: the first part trying to explore the role of the PSA/FT ratio in clustering patients with different pathologic prognostic factors, and the second to investigate the PSA/FT ratio distribution in different groups of patients according to the pathologic stage and pGS of the specimen after radical prostatectomy. The average age was 65.80 (range 51.21-77.26) years, mean PSA was 8.88 (range 1.22-44.27) μg/l, mean FT was 35.32 (range 13.70-69.30) pmol/l, and the mean PSA/FT ratio was 0.27 (range 0.04-1.48). The PSA/FT ratio significantly clustered both the pT and pGS groups. Analysis of variance for the distribution of the PSA/FT ratio was significant for the pT model groups. The mean PSA/FT ratio increased as the tumor extended and grew through the prostate gland (high-stage disease). Analysis of variance for the different distributions of the PSA/FT ratio was significant for all model pGS groups. In our investigation we also found (data not shown) that a PSA/FT ratio of ≥0.40 was strongly correlated with large extensive (pT3b+pT4) and high-grade cancers (pGS8+pGS9). Prostate cancer patients may be classified into 3 different pathologic prognostic groups according to the PSA/FT ratio: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40), and high risk (PSA/FT >0.40 and ≤1.5). The PSA/FT ratio may be considered as the marker expressing different biology groups of prostate cancer patients, and it is strongly associated with pT and pGS. Copyright © 2010 S. Karger AG, Basel.

Percentage of Cancer Volume in Biopsy Cores Is Prognostic for Prostate Cancer Death and Overall Survival in Patients Treated With Dose-Escalated External Beam Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vance, Sean M.; Stenmark, Matthew H.; Blas, Kevin

2012-07-01

Purpose: To investigate the prognostic utility of the percentage of cancer volume (PCV) in needle biopsy specimens for prostate cancer patients treated with dose-escalated external beam radiotherapy. Methods and Materials: The outcomes were analyzed for 599 men treated for localized prostate cancer with external beam radiotherapy to a minimal planning target volume dose of 75 Gy (range, 75-79.2). We assessed the effect of PCV and the pretreatment and treatment-related factors on the freedom from biochemical failure, freedom from metastasis, cause-specific survival, and overall survival. Results: The median number of biopsy cores was 7 (interquartile range, 6-12), median PCV was 10%more » (interquartile range, 2.5-25%), and median follow-up was 62 months. The PCV correlated with the National Comprehensive Cancer Network risk group and individual risk features, including T stage, prostate-specific antigen level, Gleason score, and percentage of positive biopsy cores. On log-rank analysis, the PCV stratified by quartile was prognostic for all endpoints, including overall survival. In addition, the PCV was a stronger prognostic factor than the percentage of positive biopsy cores when the two metrics were analyzed together. On multivariate analysis, the PCV predicted a worse outcome for all endpoints, including freedom from biochemical failure, (hazard ratio, 1.9; p = .0035), freedom from metastasis (hazard ratio, 1.7, p = .09), cause-specific survival (hazard ratio, 3.9, p = .014), and overall survival (hazard ratio, 1.8, p = .02). Conclusions: For patients treated with dose-escalated external beam radiotherapy, the volume of cancer in the biopsy specimen adds prognostic value for clinically relevant endpoints, particularly in intermediate- and high-risk patients. Although the PCV determination is more arduous than the percentage of positive biopsy cores, it provides superior risk stratification.« less

End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer.

PubMed

Narang, A K; Trieu, J; Radwan, N; Ram, A; Robertson, S P; He, P; Gergis, C; Griffith, E; Singh, H; DeWeese, T A; Honig, S; Annadanam, A; Greco, S; DeVille, C; McNutt, T; DeWeese, T L; Song, D Y; Tran, P T

2017-06-01

In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993 to 2006 and who had an end-of-radiation (EOR) PSA (n=688, median follow-up 11.2 years). We analyzed the association of an EOR PSA level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ⩾0.1 ng ml -1 ) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% versus 64.4%, P<0.001), 10-year MFS (84.8% versus 92.0%, P=0.003), 10-year PCSS (94.3% versus 98.2%, P=0.007) and 10-year OS (75.8% versus 82.5%, P=0.01), as compared to men with an undetectable EOR PSA. Among National Comprehensive Care Network (NCCN) intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37-14.65, P<0.001; NCCN risk level: HR 2.01, 95% CI 0.74-5.42, P=0.168). Main study limitations are retrospective study design and associated biases. EOR PSA was significantly associated with survival endpoints in men who received treatment with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation.

Sleep disruption, chronotype, shift work, and prostate cancer risk and mortality: a 30-year prospective cohort study of Finnish twins.

PubMed

Dickerman, Barbra A; Markt, Sarah C; Koskenvuo, Markku; Hublin, Christer; Pukkala, Eero; Mucci, Lorelei A; Kaprio, Jaakko

2016-11-01

Sleep disruption and shift work have been associated with cancer risk, but epidemiologic evidence for prostate cancer remains limited. We aimed to prospectively investigate the association between midlife sleep- and circadian-related parameters and later prostate cancer risk and mortality in a population-based cohort of Finnish twins. Data were drawn from the Older Finnish Twin Cohort and included 11,370 twins followed from 1981 to 2012. Over the study period, 602 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between midlife sleep duration, sleep quality, chronotype, and shift work with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were employed to account for potential familial confounding. Compared to "definite morning" types, "somewhat evening" types had a significantly increased risk of prostate cancer (HR 1.3; 95 % CI 1.1, 1.6). Chronotype significantly modified the relationship between shift work and prostate cancer risk (p-interaction <0.001). We found no significant association between sleep duration, sleep quality, or shift work and prostate cancer risk in the overall analyses and no significant association between any sleep- or circadian-related parameter and risk in co-twin analyses. Neither sleep- nor circadian-related parameters were significantly associated with prostate cancer-specific mortality. The association between sleep disruption, chronotype, and shift work with prostate cancer risk and mortality has never before been studied in a prospective study of male twins. Our findings suggest that chronotype may be associated with prostate cancer risk and modify the association between shift work and prostate cancer risk. Future studies of circadian disruption and prostate cancer should account for this individual-level characteristic.

Red maca (Lepidium meyenii) reduced prostate size in rats

PubMed Central

Gonzales, Gustavo F; Miranda, Sara; Nieto, Jessica; Fernández, Gilma; Yucra, Sandra; Rubio, Julio; Yi, Pedro; Gasco, Manuel

2005-01-01

Background Epidemiological studies have found that consumption of cruciferous vegetables is associated with a reduced risk of prostate cancer. This effect seems to be due to aromatic glucosinolate content. Glucosinolates are known for have both antiproliferative and proapoptotic actions. Maca is a cruciferous cultivated in the highlands of Peru. The absolute content of glucosinolates in Maca hypocotyls is relatively higher than that reported in other cruciferous crops. Therefore, Maca may have proapoptotic and anti-proliferative effects in the prostate. Methods Male rats treated with or without aqueous extracts of three ecotypes of Maca (Yellow, Black and Red) were analyzed to determine the effect on ventral prostate weight, epithelial height and duct luminal area. Effects on serum testosterone (T) and estradiol (E2) levels were also assessed. Besides, the effect of Red Maca on prostate was analyzed in rats treated with testosterone enanthate (TE). Results Red Maca but neither Yellow nor Black Maca reduced significantly ventral prostate size in rats. Serum T or E2 levels were not affected by any of the ecotypes of Maca assessed. Red Maca also prevented the prostate weight increase induced by TE treatment. Red Maca administered for 42 days reduced ventral prostatic epithelial height. TE increased ventral prostatic epithelial height and duct luminal area. These increases by TE were reduced after treatment with Red Maca for 42 days. Histology pictures in rats treated with Red Maca plus TE were similar to controls. Phytochemical screening showed that aqueous extract of Red Maca has alkaloids, steroids, tannins, saponins, and cardiotonic glycosides. The IR spectra of the three ecotypes of Maca in 3800-650 cm (-1) region had 7 peaks representing 7 functional chemical groups. Highest peak values were observed for Red Maca, intermediate values for Yellow Maca and low values for Black Maca. These functional groups correspond among others to benzyl glucosinolate. Conclusions Red Maca, a cruciferous plant from the highland of Peru, reduced ventral prostate size in normal and TE treated rats. PMID:15661081

Diagnostic Challenges in Prostate Cancer and 68Ga-PSMA PET Imaging: A Game Changer?

PubMed

Zaman, Maseeh uz; Fatima, Nosheen; Zaman, Areeba; Sajid, Mahwsih; Zaman, Unaiza; Zaman, Sidra

2017-10-26

Prostate cancer (PC) is the most frequent solid tumor in men and the third most common cause of cancer mortality among men in developed countries. Current imaging modalities like ultrasound (US), computerized tomography (CT), magnetic resonance imaging (MRI) and choline based positron emission (PET) tracing have disappointing sensitivity for detection of nodal metastasis and small tumor recurrence. This poses a diagnostic challenge in staging of intermediate to high risk PC and restaging of patients with biochemical recurrence (PSA >0.2 ng/ml). Gallium-68 labeled prostate specific membrane antigen (68Ga-PSMA) PET imaging has now emerged with a higher diagnostic yield. 68Ga-PSMA PET/CT or PET/MRI can be expected to offer a one-stop-shop for staging and restaging of PC. PSMA ligands labeled with alpha and beta emitters have also shown promising therapeutic efficacy for nodal, bone and visceral metastasis. Therefore a PSMA based theranostics approach for detection, staging, treatment, and follow-up of PC would appear to be highly valuable to achieve personalized PC treatment. Creative Commons Attribution License

Genomic Prostate Cancer Classifier Predicts Biochemical Failure and Metastases in Patients After Postoperative Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Den, Robert B., E-mail: Robert.Den@jeffersonhospital.org; Feng, Felix Y.; Showalter, Timothy N.

2014-08-01

Purpose: To test the hypothesis that a genomic classifier (GC) would predict biochemical failure (BF) and distant metastasis (DM) in men receiving radiation therapy (RT) after radical prostatectomy (RP). Methods and Materials: Among patients who underwent post-RP RT, 139 were identified for pT3 or positive margin, who did not receive neoadjuvant hormones and had paraffin-embedded specimens. Ribonucleic acid was extracted from the highest Gleason grade focus and applied to a high-density-oligonucleotide microarray. Receiver operating characteristic, calibration, cumulative incidence, and Cox regression analyses were performed to assess GC performance for predicting BF and DM after post-RP RT in comparison with clinical nomograms.more » Results: The area under the receiver operating characteristic curve of the Stephenson model was 0.70 for both BF and DM, with addition of GC significantly improving area under the receiver operating characteristic curve to 0.78 and 0.80, respectively. Stratified by GC risk groups, 8-year cumulative incidence was 21%, 48%, and 81% for BF (P<.0001) and for DM was 0, 12%, and 17% (P=.032) for low, intermediate, and high GC, respectively. In multivariable analysis, patients with high GC had a hazard ratio of 8.1 and 14.3 for BF and DM. In patients with intermediate or high GC, those irradiated with undetectable prostate-specific antigen (PSA ≤0.2 ng/mL) had median BF survival of >8 years, compared with <4 years for patients with detectable PSA (>0.2 ng/mL) before initiation of RT. At 8 years, the DM cumulative incidence for patients with high GC and RT with undetectable PSA was 3%, compared with 23% with detectable PSA (P=.03). No outcome differences were observed for low GC between the treatment groups. Conclusion: The GC predicted BF and metastasis after post-RP irradiation. Patients with lower GC risk may benefit from delayed RT, as opposed to those with higher GC; however, this needs prospective validation. Genomic-based models may be useful for improved decision-making for treatment of high-risk prostate cancer.« less

Relative value of race, family history and prostate specific antigen as indications for early initiation of prostate cancer screening.

PubMed

Vertosick, Emily A; Poon, Bing Ying; Vickers, Andrew J

2014-09-01

Many guidelines suggest earlier screening for prostate cancer in men at high risk, with risk defined in terms of race and family history. Recent evidence suggests that baseline prostate specific antigen is strongly predictive of the long-term risk of aggressive prostate cancer. We compared the usefulness of risk stratifying early screening by race, family history and prostate specific antigen at age 45 years. Using estimates from the literature we calculated the proportion of men targeted for early screening using family history, black race or prostate specific antigen as the criterion for high risk. We calculated the proportion of prostate cancer deaths that would occur in those men by age 75 years. Screening based on family history involved 10% of men, accounting for 14% of prostate cancer deaths. Using black race as a risk criterion involved 13% of men, accounting for 28% of deaths. In contrast, 44% of prostate cancer deaths occurred in the 10% of men with the highest prostate specific antigen at age 45 years. In no sensitivity analysis for race and family history did the ratio of risk group size to number of prostate cancer deaths in that risk group approach that of prostate specific antigen. Basing decisions for early screening on prostate specific antigen at age 45 years provided the best ratio between men screened and potential cancer deaths avoided. Given the lack of evidence that race or family history affects the relationship between prostate specific antigen and risk, prostate specific antigen based risk stratification would likely include any black men or men with a family history who are destined to experience aggressive disease. Differential screening based on risk should be informed by baseline prostate specific antigen. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The Role of Central Metabolism in Prostate Cancer Progression

DTIC Science & Technology

2013-09-01

prostate tissue for differences in tumor growth, proteomes and intermediates in polyunsaturated fatty acid (PUFA) metabolism . The use of the... MRM -based targeted proteomics. She has also learned a great deal of techniques in molecular and cell biology. As her initial study, she transfected

A hybrid strategy of offline adaptive planning and online image guidance for prostate cancer radiotherapy.

PubMed

Lei, Yu; Wu, Qiuwen

2010-04-21

Offline adaptive radiotherapy (ART) has been used to effectively correct and compensate for prostate motion and reduce the required margin. The efficacy depends on the characteristics of the patient setup error and interfraction motion through the whole treatment; specifically, systematic errors are corrected and random errors are compensated for through the margins. In online image-guided radiation therapy (IGRT) of prostate cancer, the translational setup error and inter-fractional prostate motion are corrected through pre-treatment imaging and couch correction at each fraction. However, the rotation and deformation of the target are not corrected and only accounted for with margins in treatment planning. The purpose of this study was to investigate whether the offline ART strategy is necessary for an online IGRT protocol and to evaluate the benefit of the hybrid strategy. First, to investigate the rationale of the hybrid strategy, 592 cone-beam-computed tomography (CBCT) images taken before and after each fraction for an online IGRT protocol from 16 patients were analyzed. Specifically, the characteristics of prostate rotation were analyzed. It was found that there exist systematic inter-fractional prostate rotations, and they are patient specific. These rotations, if not corrected, are persistent through the treatment fraction, and rotations detected in early fractions are representative of those in later fractions. These findings suggest that the offline adaptive replanning strategy is beneficial to the online IGRT protocol with further margin reductions. Second, to quantitatively evaluate the benefit of the hybrid strategy, 412 repeated helical CT scans from 25 patients during the course of treatment were included in the replanning study. Both low-risk patients (LRP, clinical target volume, CTV = prostate) and intermediate-risk patients (IRP, CTV = prostate + seminal vesicles) were included in the simulation. The contours of prostate and seminal vesicles were delineated on each CT. The benefit of margin reduction to compensate for both rotation and deformation in the hybrid strategy was evaluated geometrically. With the hybrid strategy, the planning margins can be reduced by 1.4 mm for LRP, and 2.0 mm for IRP, compared with the standard online IGRT only, to maintain the same 99% target volume coverage. The average relative reduction in planning target volume (PTV) based on the internal target volume (ITV) from PTV based on CTV is 19% for LRP, and 27% for IRP.

Preoperative Staging With 11C-Choline PET/CT Is Adequately Accurate in Patients With Very High-Risk Prostate Cancer.

PubMed

Schiavina, Riccardo; Bianchi, Lorenzo; Mineo Bianchi, Federico; Borghesi, Marco; Pultrone, Cristian Vincenzo; Dababneh, Hussam; Castellucci, Paolo; Ceci, Francesco; Nanni, Cristina; Gaudiano, Caterina; Fiorentino, Michelangelo; Porreca, Angelo; Chessa, Francesco; Minervini, Andrea; Fanti, Stefano; Brunocilla, Eugenio

2018-05-30

To evaluate the accuracy of 11 C-choline positron emission tomography (PET)/computed tomography (CT) for nodal staging of prostate cancer (PCa) in different populations of high-risk patients. We evaluated 262 individuals with intermediate- or high-risk PCa submitted to radical prostatectomy and extended pelvic lymph node dissection. Within men with high-risk disease, we identified a subgroup of individuals harboring very high-risk (VHR, n = 28) disease: clinical stage ≥ T2c and more than 5 cores with Gleason score 8-10; primary biopsy Gleason score of 5; 3 high-risk features; or prostate-specific antigen ≥ 30 ng/mL. The diagnostic accuracy of PET/CT and contrast-enhanced CT (CECT) was assessed after stratifying patients according to risk group classification on a patient- and anatomic region-based analysis. On patient-based analysis, considering high-risk patients (n = 155), 11 C-choline PET/CT versus CECT had sensitivity and specificity of 50% and 76% versus 21% and 92%, respectively. Considering VHR men as separate subgroups (n = 28), 11 C-choline PET/CT versus CECT had sensitivity and specificity of 71% and 93% versus 25% and 79%, respectively. Accordingly, in the VHR category, the area under the curve of 11 C-choline PET/CT versus CECT was 0.86 (95% confidence interval, 0.71-1.0) versus 0.69 (95% confidence interval, 0.52-0.86), respectively. On anatomic region-based analysis, considering the VHR group, 11 C-choline PET/CT versus CECT had sensitivity and specificity of 70.6% and 95.5% versus 35.3% and 98.5%, respectively. Patients with VHR characteristics could represent the ideal candidate to undergo disease staging with PET/CT before surgery with the highest cost efficacy. Copyright © 2018 Elsevier Inc. All rights reserved.

Relative Risks for Lethal Prostate Cancer Based on Complete Family History of Prostate Cancer Death.

PubMed

Albright, Frederick S; Stephenson, Robert A; Agarwal, Neeraj; Cannon-Albright, Lisa A

2017-01-01

There are few published familial relative risks (RR) for lethal prostate cancer. This study estimates RRs for lethal prostate cancer based on comprehensive family history data, with the goal of improving identification of those men at highest risk of dying from prostate cancer. We used a population-based genealogical resource linked to a statewide electronic SEER cancer registry and death certificates to estimate relative risks (RR) for death from prostate cancer based upon family history. Over 600,000 male probands were analyzed, representing a variety of family history constellations of lethal prostate cancer. RR estimates were based on the ratio of the observed to the expected number of lethal prostate cancer cases using internal rates. RRs for lethal prostate cancer based on the number of affected first-degree relatives (FDR) ranged from 2.49 (95% CI: 2.27, 2.73) for exactly 1 FDR to 5.30 (2.13, 10.93) for ≥3 affected FDRs. In an absence of affected FDRs, increased risk was also significant for increasing numbers of affected second-degree or third degree relatives. Equivalent risks were observed for similar maternal and paternal family history. This study provides population-based estimates of lethal prostate cancer risk based on lethal prostate cancer family history. Many family history constellations associated with two to greater than five times increased risk for lethal prostate cancer were identified. These lethal prostate cancer risk estimates hold potential for use in identification, screening, early diagnosis, and treatment of men at high risk for death from prostate cancer. Prostate77:41-48, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Outcome of Patients With Therapy-Related Acute Myeloid Leukemia With or Without a History of Myelodysplasia.

PubMed

Sasaki, Koji; Jabbour, Elias; Cortes, Jorge; Kadia, Tapan; Garcia-Manero, Guillermo; Borthakur, Gautam; Jain, Preetesh; Pierce, Sherry; Daver, Naval; Takahashi, Koichi; O'Brien, Susan; Kantarjian, Hagop; Ravandi, Farhad

2016-11-01

To learn whether an antecedent hematologic disorder (AHD) is associated with additional risk in patients with therapy-related acute myeloid leukemia (t-AML). We reviewed data of 301 patients with newly diagnosed t-AML who sought care from January 2000 to January 2014 (183 t-AML without AHD, 118 t-AML with AHD). Overall, median follow-up was 44 months. The primary malignancy was non-Hodgkin lymphoma in 92 (31%), breast cancer in 80 (27%), and prostate cancer in 49 (16%). Median relapse-free survival (RFS) in t-AML without or with AHD was 10 months and 29 months, respectively (P = .032); median overall survival (OS) was 8 months and 8 months, respectively (P = .53). Multivariate analysis for OS identified older age, poor performance status, thrombocytopenia, nonfavorable cytogenetics, and lack of response as adverse factors. The favorable-risk cohort had better RFS and OS compared to the outcomes of patients in the intermediate- and adverse-risk cohorts; the RFS and OS did not differ between intermediate- and adverse-risk cohorts. The presence of AHD did not affect OS. Copyright © 2016 Elsevier Inc. All rights reserved.

Demonstration of intermediate cells during human prostate epithelial differentiation in situ and in vitro using triple-staining confocal scanning microscopy.

PubMed

van Leenders, G; Dijkman, H; Hulsbergen-van de Kaa, C; Ruiter, D; Schalken, J

2000-08-01

In human prostate epithelium, morphologically basal and luminal cells can be discriminated. The basal cell layer that putatively contains progenitor cells of the secretory epithelium is characterized by the expression of keratins (K) 5 and 14. Luminal cells represent the secretory compartment of the epithelium and express K8 and 18. We developed a technique for the simultaneous analysis of K5, 14, and 18 to identify intermediate cell stages in the prostate epithelium and to study the dynamic aspects of its differentiation in vitro. Nonmalignant prostate tissue and primary epithelial cultures were immunohistochemically characterized using triple staining with antibodies for K5, K14, and K18. Antibodies for K18 and K5 were conjugated directly with fluorochromes Alexa 488 and 546. K14 was visualized indirectly with streptavidin-Cy5. Keratin expression was analyzed by confocal scanning microscopy. The occurrence of exocrine and neuroendocrine differentiation in culture was determined via antibodies to prostate-specific antigen (PSA), chromogranin A, and serotonin. We found that basal cells expressed either K5(++)/14(++)/18+ or K5(++)/18+. The majority of luminal cells expressed K18(++), but colocalization of K5+/18(++) were recognized. Epithelial monolayer cultures predominantly revealed the basal cell phenotype K5(++)/14(++)/18+, whereas intermediate subpopulations expressing K5+/14+/18(++) and K5+/18(++) were also identified. On confluence, differentiation was induced as multicellular gland-like buds, and extensions became evident on top of the monolayer. These structures were composed of K18(++)- and K5+/18(+)-positive cell clusters surrounded by phenotypically basal cells. Few multicellular structures and cells in the monolayer showed exocrine differentiation (PSA+), but expression of chromogranin A and serotonin was absent. We conclude that simultaneous evaluation of keratin expression is useful for analyzing epithelial differentiation in the prostate. During this process, putative stem cells phenotypically resembling K5(++)/14(++)/18+ differentiate toward luminal cells (K18(++)) via intermediate cell stages, as identified by up-regulation of K18 and down-regulation of K5 and 14.

Prostate Cancer Patient Perspectives on the Use of Information in Treatment Decision-Making: A Systematic Review and Qualitative Meta-synthesis

PubMed Central

Kandasamy, Sujane; Khalid, Ahmad Firas; Majid, Umair; Vanstone, Meredith

2017-01-01

Background Men with low- to intermediate-risk prostate cancer are typically asked to choose from a variety of treatment options, including active surveillance, radical prostatectomy, or brachytherapy. The Prolaris cell cycle progression test is intended to provide additional information on personal risk status to assist men with prostate cancer in their choice of treatment. To assist with assessing that new technology, this report synthesizes qualitative research on how men with prostate cancer use information to make decisions about treatment options. Methods We performed a systematic review and qualitative meta-synthesis to retrieve and synthesize findings across primary qualitative studies that report on patient perspectives during prostate cancer treatment decision-making. Results Of 8,610 titles and abstracts reviewed, 29 studies are included in this report. Most men diagnosed with prostate cancer express that their information-seeking pathway extends beyond the medical information received from their health care provider. They access other social resources to attain additional medical information, lived-experience information, and medical administrative information to help support their final treatment decision. Men value privacy, trust, honesty, control, power, organization, and open communication during interactions with their health care providers. They also emphasize the importance of gaining comfort with their treatment choice, having a chance to confirm their health care provider's recommendations (validation of treatment plan), and exercising their preferred level of independence in the treatment decision-making process. Conclusions Although each prostate cancer patient is unique, studies suggest that most patients seek extensive information to help inform their treatment decisions. This may happen before, during, and after the treatment choice is made. Given the amount of information patients may access, it is important that they also establish the trustworthiness of the various types and sources of information. When information conflicts, patients may be unsure about how to proceed. Open collaboration between patients and their health care providers can help patients manage and navigate their concerns so that their values and perspectives are captured in their treatment choices. PMID:28572868

SU-F-J-11: Radiobiologically Optimized Patient Localization During Prostate External Beam Localization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Y; Gardner, S; Liu, C

2016-06-15

Purpose: To present a novel positioning strategy which optimizes radiation delivery with radiobiological response knowledge, and to evaluate its application during prostate external beam radiotherapy. Methods: Ten patients with low or intermediate risk prostate cancer were evaluated retrospectively in this IRB-approved study. For each patient, a VMAT plan was generated on the planning CT (PCT) to deliver 78 Gy in 39 fractions with PTV = prostate + 7 mm margin, except for 5mm in the posterior direction. Five representative pretreatment CBCT images were selected for each patient, and prostate, rectum, and bladder were delineated on all CBCT images. Each CBCTmore » was auto-registered to the corresponding PCT. Starting from this auto-matched position (AM-position), a search for optimal treatment position was performed utilizing a score function based on radiobiological and dosimetric indices (D98-DTV, NTCP-rectum, and NTCP-bladder) for the daily target volume (DTV), rectum, and bladder. DTV was defined as prostate + 4 mm margin to account for intra-fraction motion as well as contouring variability on CBCT. We termed the optimal treatment position the radiobiologically optimized couch shift position (ROCS-position). Results: The indices, averaged over the 10 patients’ treatment plans, were (mean±SD): 77.7±0.2 Gy (D98-PTV), 12.3±2.7% (NTCP-rectum), and 53.2±11.2% (NTCP-bladder). The corresponding values calculated on all 50 CBCT images at the AM-positions were 72.9±11.3 Gy (D98-DTV), 15.8±6.4% (NTCP-rectum), and 53.0±21.1% (NTCP-bladder), respectively. In comparison, calculated on CBCT at the ROCS-positions, the indices were 77.0±2.1 Gy (D98-DTV), 12.1±5.7% (NTCP-rectum), and 60.7±16.4% (NTCP-bladder). Compared to autoregistration, ROCS-optimization recovered dose coverage to target volume and lowered the risk to rectum. Moreover, NTCPrectum for one patient remained high after ROCS-optimization and therefore could potentially benefit from adaptive planning. Conclusion: These encouraging results illustrate the potential utility of applying radiobiologically optimized correction for online image-guided radiotherapy of prostate patients.« less

Focal therapy in prostate cancer: the current situation

PubMed Central

Jácome-Pita, FX; Sánchez-Salas, R; Barret, E; Amaruch, N; Gonzalez-Enguita, C; Cathelineau, X

2014-01-01

Prostate cancer is one of the most significant pathologies in the field of urology. The adoption of screening strategies and improvements in biopsies have resulted in an increase in early-stage tumour detection. Radical global therapies provide very good oncological results in localised prostate cancer. However, excess treatment in low- and, in some cases, intermediate-risk groups affects the quality of life of these patients. In the case of localised prostate cancer, focal therapies offer a minimally invasive option with good results with respect to established treatments. Although this is currently not a standard treatment, it represents the therapeutic approach with the greatest potential. This literature review has the following objectives: to define selection criteria for patients who are candidates for focal therapy, to assess the current situation and results of the different therapeutic options, and to define procedures in cases of recurrence and for follow-ups. We concluded that focal therapy is a viable therapeutic alternative for localised prostate cancer, specifically cryosurgery and high-intensity targeted ultrasound, which have acceptable oncologic results and a lower comorbidity compared with global treatments. Studies with a high level of scientific evidence are still needed to validate these results. Acquisition of evidence A search was carried out on the Medline (PubMed), EMBASE, Web of Science and Cochrane databases of all papers published before 31 July 2013. We included clinical studies and literature reviews that evaluated primary focal therapy for prostate cancer confirmed by biopsy and excluded focal rescue therapy studies. The keywords used were focal therapy and prostate cancer. Initially, we found 42 articles; 15 studies were excluded because they did not meet the minimum criteria for inclusion. A total of 1350 cases were treated throughout 27 studies. PMID:24944577

Body mass index influences prostate cancer risk at biopsy in Japanese men.

PubMed

Masuda, Hitoshi; Kagawa, Makoto; Kawakami, Satoru; Numao, Noboru; Matsuoka, Yoh; Yokoyama, Minato; Yamamoto, Shinya; Yonese, Junji; Fukui, Iwao; Kihara, Kazunori

2013-07-01

To determine the relationship between body mass index and prostate cancer risk at biopsy in Japanese men, and to compared the risk with that of Caucasian men. We retrospectively evaluated 3966 men with prostate-specific antigen levels from 2.5 to 19.9 ng/mL who underwent an initial extended prostate biopsy. Using logistic regression, odds ratios of each body mass index category for risk of prostate cancer and high-grade disease (Gleason score ≥4 + 3) were estimated after controlling for age, prostate-specific antigen, %free prostate-specific antigen, prostate volume, digital rectal examination findings, family history of prostate cancer and the number of biopsy cores. Patients were divided into six categories according to their body mass index (kg/m(2) ) as follows: <21.0, 21.0-22.9, 23.0-24.9, 25.0-26.9, 27.0-29.9 and ≥30.0. A significant positive association was observed between body mass index and prostate cancer risk at biopsy, with an increased risk observed in men whose body mass index was ≥27.0 compared with the reference group. A significantly increased risk starting at body mass index ≥25.0 was found in high-grade disease. In contrast to our results, there has been no reported increase in the risk of prostate cancer at biopsy in Caucasians within the overweight range (body mass index of 25.0-29.9 based on World Health Organization classification). Japanese men within the overweight body mass index range who have an elevated prostate-specific antigen level also have a significant risk of harboring prostate cancer, especially high-grade disease. Overweight Japanese might be at greater prostate cancer risk at biopsy than overweight Caucasians. © 2012 The Japanese Urological Association.

Desquamation takes center stage at the origin of proliferative inflammatory atrophy, epithelial-mesenchymal transition, and stromal growth in benign prostate hyperplasia.

PubMed

Ferrucci, Danilo; Biancardi, Manoel F; Nishan, Umar; Rosa-Ribeiro, Rafaela; Carvalho, Hernandes F

2017-11-01

In this commentary, we propose a relationship between desquamation, initially described as the collective detachment and deletion of epithelial cell in the prostate gland after castration, and proliferative inflammatory atrophy (PIA) and stromal growth in benign prostate hyperplasia (BPH). First, in response to diverse stimuli, including inflammatory mediators, epithelial cells desquamate and leave a large surface of the luminal side of the basement membrane (BM) exposed. Basal cells are activated into intermediate-type cells, which change morphology to cover and remodel the exposed BM (simple atrophy) to a new physiological demand (such as in the hypoandrogen environment, simulated by surgical and/or chemical castration) and/or to support re-epithelialization (under normal androgen levels). In the presence of inflammation (that might be the cause of desquamation), the intermediate-type cells proliferate and characterize PIA. Second, in other circumstances, desquamation is an early step of epithelial-to-mesenchymal transition (EMT), which contributes to stromal growth, as suggested by some experimental models of BPH. The proposed associations correlate unexplored cell behaviors and reveal the remarkable plasticity of the prostate epithelium that might be at the origin of prostate diseases. © 2017 International Federation for Cell Biology.

Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.

PubMed

Amin Al Olama, Ali; Benlloch, Sara; Antoniou, Antonis C; Giles, Graham G; Severi, Gianluca; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Muir, Kenneth; Schleutker, Johanna; Henderson, Brian E; Haiman, Christopher A; Schumacher, Fredrick R; Pashayan, Nora; Pharoah, Paul D P; Ostrander, Elaine A; Stanford, Janet L; Batra, Jyotsna; Clements, Judith A; Chambers, Suzanne K; Weischer, Maren; Nordestgaard, Børge G; Ingles, Sue A; Sorensen, Karina D; Orntoft, Torben F; Park, Jong Y; Cybulski, Cezary; Maier, Christiane; Doerk, Thilo; Dickinson, Joanne L; Cannon-Albright, Lisa; Brenner, Hermann; Rebbeck, Timothy R; Zeigler-Johnson, Charnita; Habuchi, Tomonori; Thibodeau, Stephen N; Cooney, Kathleen A; Chappuis, Pierre O; Hutter, Pierre; Kaneva, Radka P; Foulkes, William D; Zeegers, Maurice P; Lu, Yong-Jie; Zhang, Hong-Wei; Stephenson, Robert; Cox, Angela; Southey, Melissa C; Spurdle, Amanda B; FitzGerald, Liesel; Leongamornlert, Daniel; Saunders, Edward; Tymrakiewicz, Malgorzata; Guy, Michelle; Dadaev, Tokhir; Little, Sarah J; Govindasami, Koveela; Sawyer, Emma; Wilkinson, Rosemary; Herkommer, Kathleen; Hopper, John L; Lophatonanon, Aritaya; Rinckleb, Antje E; Kote-Jarai, Zsofia; Eeles, Rosalind A; Easton, Douglas F

2015-07-01

Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. ©2015 American Association for Cancer Research.

Heterogeneity in risk of prostate cancer: A Swedish population-based cohort study of competing risks and type 2 diabetes mellitus.

PubMed

Häggström, Christel; Van Hemelrijck, Mieke; Garmo, Hans; Robinson, David; Stattin, Pär; Rowley, Mark; Coolen, Anthony C C; Holmberg, Lars

2018-05-09

Most previous studies of prostate cancer have not taken into account that men in the studied populations are also at risk of competing event, and that these men may have different susceptibility to prostate cancer risk. The aim of this study was to investigate heterogeneity in risk of prostate cancer, using a recently developed latent class regression method for competing risks. We further aimed to elucidate the association between type 2 diabetes mellitus (T2DM) and prostate cancer risk, and to compare the results with conventional methods for survival analysis. We analysed the risk of prostate cancer in 126,482 men from the comparison cohort of the Prostate Cancer Data base Sweden (PCBaSe) 3.0. During a mean follow-up of 6 years 6,036 men were diagnosed with prostate cancer and 22,393 men died. We detected heterogeneity in risk of prostate cancer with two distinct latent classes in the study population. The smaller class included 9% of the study population in which men had a higher risk of prostate cancer and the risk was stronger associated with class membership than any of the covariates included in the study. Moreover, we found no association between T2DM and risk of prostate cancer after removal of the effect of informative censoring due to competing risks. The recently developed latent class for competing risks method could be used to provide new insights in precision medicine with the target to classify individuals regarding different susceptibility to a particular disease, reaction to a risk factor or response to treatment. This article is protected by copyright. All rights reserved. © 2018 UICC.

Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer.

PubMed

Loeb, Stacy; Shin, Sanghyuk S; Broyles, Dennis L; Wei, John T; Sanda, Martin; Klee, George; Partin, Alan W; Sokoll, Lori; Chan, Daniel W; Bangma, Chris H; van Schaik, Ron H N; Slawin, Kevin M; Marks, Leonard S; Catalona, William J

2017-07-01

To examine the use of the Prostate Health Index (PHI) as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicentre US study. The study population included 728 men, with prostate-specific antigen (PSA) levels of 2-10 ng/mL and a negative digital rectal examination, enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score ≥7. First, we evaluated whether the addition of PHI improves the performance of currently available risk calculators (the Prostate Cancer Prevention Trial [PCPT] and European Randomised Study of Screening for Prostate Cancer [ERSPC] risk calculators). We also designed and internally validated a new PHI-based multivariable predictive model, and created a nomogram. Of 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. The PHI predicted the risk of aggressive prostate cancer across the spectrum of values. Adding PHI significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, previous biopsy, prostate volume, PSA and PHI, with an area under the curve of 0.746. The bootstrap-corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision-curve analysis. Using PHI as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alizadeh, Moein; Sylvestre, Marie-Pierre; Zilli, Thomas

2012-07-15

Purpose: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostatemore » cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level <10 ng/mL (odds ratio, 2.9; 95% confidence interval, 1.3-6.8; p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08-0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02-0.59, p = .02). Conclusion: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.« less

Dietary intakes of carbohydrates in relation to prostate cancer risk: a prospective study in the Malmö Diet and Cancer cohort.

PubMed

Drake, Isabel; Sonestedt, Emily; Gullberg, Bo; Ahlgren, Göran; Bjartell, Anders; Wallström, Peter; Wirfält, Elisabet

2012-12-01

Dietary carbohydrates have been implicated in relation to prostate cancer. Our objective was to examine the associations between dietary intakes of carbohydrates, fiber, and their food sources and risk of prostate cancer, overall and by case severity, in the Malmö Diet and Cancer cohort. The analysis included 8128 men aged 45-73 y without a history of cancer, cardiovascular disease, or diabetes and who were classified as adequate energy reporters. After a median follow-up time of 15 y, prostate cancer was diagnosed in 817 men. We used Cox proportional hazards regression to model associations between energy-adjusted nutrient and food intakes with risk of incident prostate cancer, with competing risk of death from non-prostate cancer causes taken into account. After adjustment for age and other known or potential risk factors, we observed no associations between total carbohydrates or dietary fiber and prostate cancer. We observed positive associations between the intake of low-fiber cereals with overall and low-risk prostate cancer and between intakes of cake and biscuits and rice and pasta with low-risk prostate cancer (all P-trend < 0.05). A high intake compared with zero consumption of sugar-sweetened beverages was associated with increased risk of symptomatic prostate cancer (HR: 1.38; 95% CI: 1.04, 1.84). Results from this large study with high-validity dietary data suggest that a high intake of refined carbohydrates may be associated with increased risk of prostate cancer. However we observed no significant associations with high-risk prostate cancer, and not all foods that are typically high in refined carbohydrates were associated with prostate cancer.

Optimizing D'Amico risk groups in radical prostatectomy through the addition of magnetic resonance imaging data.

PubMed

Algarra, R; Zudaire, B; Tienza, A; Velis, J M; Rincón, A; Pascual, I; Zudaire, J

2014-11-01

To improve the predictive efficacy of the D'Amico risk classification system with magnetic resonance imaging (MRI) of the pelvis. We studied 729 patients from a series of 1310 radical prostatectomies for T1-T2 prostate cancer who underwent staging pelvic MRI. Each patient was classified with T2, T3a or T3b MRI, and N (+) patients were excluded. We identified the therapeutic factors that affected the biochemical progression-free survival (BPFS) time (prostate specific antigen [PSA] levels>0.4ng/mL) using a univariate and multivariate study with Cox models. We attempted to improve the predictive power of the D'Amico model (low risk: T1; Gleason 2-6; PSA levels<10ng/mL; intermediate risk: T2 or Gleason 7 or PSA levels 10-20ng/mL; high risk: T3 or Gleason 8-10 or PSA levels>20ng/mL). In the univariate study, the clinical factors that influenced BPFS were the following: Gleason 7 (HR: 1.7); Gleason 8-10 (HR: 2.9); T2 (HR: 1.6); PSA levels 10-20 (HR: 2); PSA levels>20 (HR: 4.3); D'Amico intermediate (HR: 2.1) and high (HR: 4.8) risk; T3a MRI (HR: 2.3) and T3b MRI (HR: 4.5). In the multivariate study, the only variables that affected BPFS were the following: D'Amico intermediate risk (HR: 2; 95% CI 1.2-3.3); D'Amico high risk (HR: 4.1; 95% CI 2.4-6.8); T3a MRI (HR: 1.9; 95% CI 1.2-2.9) and T3b MRI (HR: 3.9; 95% CI 2.5-6.1). Predictive model: Using the multivariate Cox models, we assessed the weight of each variable. A value of 1 was given to D'Amico low risk and T2 MRI; a value of 2 was given to D'Amico intermediate risk and T3a MRI and a value 3 was given to D'Amico high risk and T3b MRI. Each patient had a marker that varied between 2 and 6. The best model included 3 groups, as follows: 494 (67.7%) patients in group 1, with a score of 2-3 points (HR, 1), a BPFS of 86%±2% and 79%±2% at 5 and 10 years, respectively; 179 (24.6%) patients in group 2, with a score of 4 points (HR, 3), a BPFS of 60%±4% and 54%±5% at 5 and 10 years, respectively; and 56 (7.7%) patients in group 3, with a score of 5-6 points (HR, 9.3), a BPFS of 29%±8% and 19%±7% at 5 and 10 years, respectively. The median BPFS time was 1.5 years. MRI data significantly improves the predictive capacity of BPFS when using the D'Amico model data. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Molecular Characterization of Indolent Prostate Cancer

DTIC Science & Technology

2016-12-01

prostate - specific antigen (PSA) test, and treated aggressively following diagnosis, leading to the contemporary problem of prostate cancer over-diagnosis... specific purpose of comparing low- risk and high-risk prostate cancer. Figure 3 shows the mapping rates for exon, intron, and inter-genic sequences. The...FFPE specimens, for the specific comparison of low-risk and high-risk prostate cancer. 5. Identified sufficient number of biopsy cases and sections

Prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in active surveillance patients.

PubMed

Iremashvili, Viacheslav; Barney, Shane L; Manoharan, Murugesan; Kava, Bruce R; Parekh, Dipen J; Punnen, Sanoj

2016-04-01

To analyze the association between prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in prostate cancer patients on active surveillance, and to study the effect of prediagnostic prostate-specific antigen values on the predictive performance of prostate-specific antigen velocity and prostate-specific antigen doubling time. The study included 137 active surveillance patients with two or more prediagnostic prostate-specific antigen levels measured over a period of at least 3 months. Two sets of analyses were carried out. First, the association between prostate-specific antigen kinetics calculated using only the prediagnostic prostate-specific antigen values and the risk of biopsy progression was studied. Second, using the same cohort of patients, the predictive value of prostate-specific antigen kinetics calculated using only post-diagnostic prostate-specific antigens and compared with that of prostate-specific antigen kinetics based on both pre- and post-diagnostic prostate-specific antigen levels was analyzed. Of 137 patients included in the analysis, 37 (27%) had biopsy progression over a median follow-up period of 3.2 years. Prediagnostic prostate-specific antigen velocity of more than 2 ng/mL/year and 3 ng/mL/year was statistically significantly associated with the risk of future biopsy progression. However, after adjustment for baseline prostate-specific antigen density, these associations were no longer significant. None of the tested prostate-specific antigen kinetics based on combined pre- and post-diagnostic prostate-specific antigen values were statistically significantly associated with the risk of biopsy progression. Historical prediagnostic prostate-specific antigens seems to be not clinically useful in patients diagnosed with low-risk prostate cancer on active surveillance. © 2016 The Japanese Urological Association.

The influence of family history on cognitive heuristics, risk perceptions, and prostate cancer screening behavior.

PubMed

McDowell, Michelle E; Occhipinti, Stefano; Chambers, Suzanne K

2013-11-01

To examine how family history of prostate cancer, risk perceptions, and heuristic decision strategies influence prostate cancer screening behavior. Men with a first-degree family history of prostate cancer (FDRs; n = 207) and men without a family history (PM; n = 239) completed a Computer Assisted Telephone Interview (CATI) examining prostate cancer risk perceptions, PSA testing behaviors, perceptions of similarity to the typical man who gets prostate cancer (representativeness heuristic), and availability of information about prostate cancer (availability heuristic). A path model explored family history as influencing the availability of information about prostate cancer (number of acquaintances with prostate cancer and number of recent discussions about prostate cancer) to mediate judgments of risk and to predict PSA testing behaviors and family history as a moderator of the relationship between representativeness (perceived similarity) and risk perceptions. FDRs reported greater risk perceptions and a greater number of PSA tests than did PM. Risk perceptions predicted increased PSA testing only in path models and was significant only for PM in multi-Group SEM analyses. Family history moderated the relationship between similarity perceptions and risk perceptions such that the relationship between these variables was significant only for FDRs. Recent discussions about prostate cancer mediated the relationships between family history and risk perceptions, and the number of acquaintances men knew with prostate cancer mediated the relationship between family history and PSA testing behavior. Family history interacts with the individuals' broader social environment to influence risk perceptions and screening behavior. Research into how risk perceptions develop and what primes behavior change is crucial to underpin psychological or public health intervention that seeks to influence health decision making.

Late Urinary Side Effects 10 Years After Low-Dose-Rate Prostate Brachytherapy: Population-Based Results From a Multiphysician Practice Treating With a Standardized Protocol and Uniform Dosimetric Goals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keyes, Mira, E-mail: mkeyes@bccancer.bc.ca; Miller, Stacy; Pickles, Tom

2014-11-01

Purpose: To determine late urinary toxicity (>12 months) in a large cohort of uniformly treated low-dose-rate prostate brachytherapy patients. Methods and Materials: From 1998 to 2009, 2709 patients with National Comprehensive Cancer Network–defined low-risk and low-tier intermediate-risk prostate cancer were treated with Iodine 125 ({sup 125}I) low-dose-rate prostate brachytherapy; 2011 patients with a minimum of 25 months of follow-up were included in the study. Baseline patients, treatment, implant factors, and late urinary toxicity (Radiation Therapy Oncology Group [RTOG] grading system and International Prostate Symptom Score [IPSS]) were recorded prospectively. Time to IPSS resolution, late RTOG genitourinary toxicity was examined with Kaplan-Meier andmore » log-rank tests. Cox proportional hazards regression was done for individual covariates and multivariable models. Results: Median follow-up was 54.5 months (range, 2-13 years). Actuarial toxicity rates reached 27% and 10% (RTOG ≥2 and ≥3, respectively) at 9-13 years. Symptoms resolved quickly in the majority of patients (88% in 6-12 months). The prevalence of RTOG 0, 1, 2, 3, and 4 toxicity with a minimum of 7 years' follow-up was 70%, 21%, 6.4%, 2.3%, and 0.08%, respectively. Patients with a larger prostate volume, higher baseline IPSS, higher D90, acute toxicity, and age >70 years had more late RTOG ≥2 toxicity (all P≤.02). The IPSS resolved slower in patients with lower baseline IPSS and larger ultrasound prostate volume, those not receiving androgen deprivation therapy, and those with higher D90. The crude rate of RTOG 3 toxicity was 6%. Overall the rate of transurethral resection of the prostate was 1.9%; strictures, 2%; incontinence, 1.3%; severe symptoms, 1.8%; late catheterization, 1.3%; and hematuria, 0.8%. The majority (80%) resolved their symptoms in 6-12 months. Conclusion: Long-term urinary toxicity after brachytherapy is low. Although actuarial rates increase with longer follow-up (27% RTOG 2 and 10% RTOG 3 at 13 years), symptoms resolve relatively quickly; between 5 and 13 years' follow-up, >90% of patients have minimal urinary toxicity. Refining patient selection criteria, planning, and treatment delivery may further reduce toxicity.« less

Sociodemographic disparities in the utilization of proton therapy for prostate cancer at an urban academic center.

PubMed

Woodhouse, Kristina D; Hwang, Wei-Ting; Vapiwala, Neha; Jain, Akansha; Wang, Xingmei; Both, Stefan; Shah, Meera; Frazier, Marquise; Gabriel, Peter; Christodouleas, John P; Tochner, Zelig; Deville, Curtiland

2017-01-01

Despite increasing use, proton therapy (PT) remains a relatively limited resource. The purpose of this study was to assess clinical and demographic differences in PT use for prostate cancer compared to intensity modulated radiation therapy (IMRT) at a single institution. All patients with low- and intermediate-risk prostate cancer (N = 633) who underwent definitive radiation therapy between 2010 and 2015 were divided into PT (n = 508) and IMRT (n = 125) comparison groups and compared using χ 2 and independent sample t tests. Univariable and multivariable logistic regression analyses were conducted to assess the associations between PT use and demographic, clinical, and treatment characteristics. The PT and IMRT cohorts varied by age, race, poverty, distance, treatment year, and treating physician. Patients who underwent IMRT were more likely to be older (mean age, 66 vs. 68 years), black (51% vs. 75%), and living in poverty or close to the facility (mean distance between residence and facility, 90 vs. 21 miles; P < .05). Prostate-specific antigen, prostate volume, and International Index of Erectile Function were significantly higher in the IMRT cohort ( P < .05), but insurance type, risk group, tumor stage, Gleason score, and patient-reported urinary and bowel scores did not differ significantly ( P > .05). Patients who underwent PT were more likely to receive hypofractionated therapy and less likely to receive androgen deprivation therapy ( P < .01). On multivariable analysis, black (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.15-0.57) and other race (OR, 0.42; 95% CI, 0.20-0.90); distance (OR, 1.14; 95% CI, 1.06-1.24); treatment years 2011 (OR, 4.87; 95% CI, 2.23-10.6), 2012 (OR, 8.27; 95% CI, 3.43-19.9), and 2014 (OR, 4.44; 95% CI, 1.94-10.2) relative to 2010; and a single treating physician (OR, 0.38; 95% CI, 0.18-0.81) relative to the reference physician with the highest rate of use were associated with PT use, whereas clinical factors such as prostate-specific antigen, prostate volume, International Index of Erectile Function, and androgen deprivation therapy were not. Sociodemographic disparities exist in PT use for prostate cancer at an urban academic institution. Further investigation of potential barriers to access is warranted to ensure equitable distribution across all demographic groups.

Influence of Androgen Deprivation Therapy on All-Cause Mortality in Men With High-Risk Prostate Cancer and a History of Congestive Heart Failure or Myocardial Infarction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Paul L., E-mail: pnguyen@LROC.harvard.edu; Chen, Ming-Hui; Beckman, Joshua A.

Purpose: It is unknown whether the excess risk of all-cause mortality (ACM) observed when androgen deprivation therapy (ADT) is added to radiation for men with prostate cancer and a history of congestive heart failure (CHF) or myocardial infarction (MI) also applies to those with high-risk disease. Methods and Materials: Of 14,594 men with cT1c-T3aN0M0 prostate cancer treated with brachytherapy-based radiation from 1991 through 2006, 1,378 (9.4%) with a history of CHF or MI comprised the study cohort. Of these, 22.6% received supplemental external beam radiation, and 42.9% received a median of 4 months of neoadjuvant ADT. Median age was 71.8more » years. Median follow-up was 4.3 years. Cox multivariable analysis tested for an association between ADT use and ACM within risk groups, after adjusting for treatment factors, prognostic factors, and propensity score for ADT. Results: ADT was associated with significantly increased ACM (adjusted hazard ratio [AHR] = 1.76; 95% confidence interval [CI], 1.32-2.34; p = 0.0001), with 5-year estimates of 22.71% with ADT and 11.62% without ADT. The impact of ADT on ACM by risk group was as follows: high-risk AHR = 2.57; 95% CI, 1.17-5.67; p = 0.019; intermediate-risk AHR = 1.75; 95% CI, 1.13-2.73; p = 0.012; low-risk AHR = 1.52; 95% CI, 0.96-2.43; p = 0.075). Conclusions: Among patients with a history of CHF or MI treated with brachytherapy-based radiation, ADT was associated with increased all-cause mortality, even for patients with high-risk disease. Although ADT has been shown in Phase III studies to improve overall survival in high-risk disease, the small subgroup of high-risk patients with a history of CHF or MI, who represented about 9% of the patients, may be harmed by ADT.« less

Prostate calculi in cancer and BPH in a cohort of Korean men: presence of calculi did not correlate with cancer risk

PubMed Central

Hwang, Eu-Chang; Choi, Hyang-Sik; Im, Chang-Min; Jung, Seung-Il; Kim, Sun-Ouck; Kang, Taek-Won; Kwon, Dong-Deuk; Park, Kwang-Sung; Ryu, Soo-Bang

2010-01-01

Prostatic calculi are common and are associated with inflammation of the prostate. Recently, it has been suggested that this inflammation may be associated with prostate carcinogenesis. The aim of this study was to investigate the relationship between prostatic calculi and prostate cancer (PCa) in prostate biopsy specimens. We retrospectively analyzed 417 consecutive patients who underwent transrectal ultrasonography (TRUS) and prostate biopsies between January 2005 and January 2008. Based on the biopsy findings, patients were divided into benign prostatic hyperplasia and PCa groups. TRUS was used to detect prostatic calculi and to measure prostate volume. The correlations between PCa risk and age, serum total PSA levels, prostate volume, and prostatic calculi were analyzed. Patient age and PSA, as well as the frequency of prostatic calculi in the biopsy specimens, differed significantly between both the groups (P < 0.05). In the PCa group, the Gleason scores (GSs) were higher in patients with prostatic calculi than in patients without prostatic calculi (P = 0.023). Using multivariate logistic regression analysis, we found that patient age, serum total PSA and prostate volume were risk factors for PCa (P = 0.001), but that the presence of prostatic calculi was not associated with an increased risk of PCa (P = 0.13). In conclusion, although the presence of prostatic calculi was not shown to be a risk factor for PCa, prostatic calculi were more common in patients with PCa and were associated with a higher GS among these men. PMID:20037598

Intermediate and longer-term outcomes from a prospective active-surveillance program for favorable-risk prostate cancer. Tosoian JJ, Mamawala M, Epstein JI, Landis P, Wolf S, Trock BJ, Carter HB.J Clin Oncol. 2015 Oct 20;33(30):3379-85. [Epub 2015 Aug 31]. doi: 10.1200/JCO.2015.62.5764.

PubMed

Scott, Eggener; Mamawala, M; Epstein, J I; Landis, P; Wolf, S; Trock; Carter, H B

2017-03-01

To assess long-term outcomes of men with favorable-risk prostate cancer in a prospective, active surveillance program. Curative intervention was recommended for disease reclassification to higher cancer grade or volume on prostate biopsy. Primary outcomes were overall, cancer-specific, and metastasis-free survival. Secondary outcomes were the cumulative incidence of reclassification and curative intervention. Factors associated with grade reclassification and curative intervention were evaluated in a Cox proportional hazards model. A total of 1,298 men (median age = 66y) with a median follow-up of 5 years (range: 0.01-18.00y) contributed 6,766 person-years of follow-up since 1995. Overall, cancer-specific, and metastasis-free survival rates were 93%, 99.9%, and 99.4%, respectively, at 10 years and 69%, 99.9%, and 99.4%, respectively, at 15 years. The cumulative incidence of grade reclassification was 26% at 10 years and was 31% at 15 years; cumulative incidence of curative intervention was 50% at 10 years and was 57% at 15 years. The median treatment-free survival was 8.5 years (range: 0.01-18y). Factors associated with grade reclassification were older age (hazard ratio [HR] = 1.03 for each additional year; 95% CI: 1.01-1.06), prostate-specific antigen density (HR = 1.21 per 0.1 unit increase; 95% CI: 1.12-1.46), and greater number of positive biopsy cores (HR = 1.47 for each additional positive core; 95% CI: 1.26-1.69). Factors associated with intervention were prostate-specific antigen density (HR = 1.38 per 0.1 unit increase; 95% CI: 1.22-1.56) and a greater number of positive biopsy cores (HR = 1.35 for one additional positive core; 95% CI: 1.19-1.53). Men with favorable-risk prostate cancer should be informed of the low likelihood of harm from their diagnosis and should be encouraged to consider surveillance rather than curative intervention. Copyright © 2017. Published by Elsevier Inc.

Quality assurance of HDR prostate plans: program implementation at a community hospital.

PubMed

Rush, Jennifer B; Thomas, Michael D

2005-01-01

Adenocarcinoma of the prostate is currently the most commonly diagnosed cancer in men in the United States, and the second leading cause of cancer mortality. The utilization of radiation therapy is regarded as the definitive local therapy of choice for intermediate- and high-risk disease, in which there is increased risk for extracapsular extension, seminal vesicle invasion, or regional node involvement. High-dose-rate (HDR) brachytherapy is a logical treatment modality to deliver the boost dose to an external beam radiation therapy (EBRT) treatment to increase local control rates. From a treatment perspective, the utilization of a complicated treatment delivery system, the compressed time frame in which the procedure is performed, and the small number of large dose fractions make the implementation of a comprehensive quality assurance (QA) program imperative. One aspect of this program is the QA of the HDR treatment plan. Review of regulatory and medical physics professional publications shows that substantial general guidance is available. We provide some insight to the implementation of an HDR prostate plan program at a community hospital. One aspect addressed is the utilization of the low-dose-rate (LDR) planning system and the use of existing ultrasound image sets to familiarize the radiation therapy team with respect to acceptable HDR implant geometries. Additionally, the use of the LDR treatment planning system provided a means to prospectively determine the relationship between the treated isodose volume and the product of activity and time for the department's planning protocol prior to the first HDR implant. For the first 12 HDR prostate implants, the root-mean-square (RMS) deviation was 3.05% between the predicted product of activity and time vs. the actual plan values. Retrospective re-evaluation of the actual implant data reduced the RMS deviation to 2.36%.

Decision-making tools in prostate cancer: from risk grouping to nomograms.

PubMed

Fontanella, Paolo; Benecchi, Luigi; Grasso, Angelica; Patel, Vipul; Albala, David; Abbou, Claude; Porpiglia, Francesco; Sandri, Marco; Rocco, Bernardo; Bianchi, Giampaolo

2017-12-01

Prostate cancer (PCa) is the most common solid neoplasm and the second leading cause of cancer death in men. After the Partin tables were developed, a number of predictive and prognostic tools became available for risk stratification. These tools have allowed the urologist to better characterize this disease and lead to more confident treatment decisions for patients. The purpose of this study is to critically review the decision-making tools currently available to the urologist, from the moment when PCa is first diagnosed until patients experience metastatic progression and death. A systematic and critical analysis through Medline, EMBASE, Scopus and Web of Science databases was carried out in February 2016 as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was conducted using the following key words: "prostate cancer," "prediction tools," "nomograms." Seventy-two studies were identified in the literature search. We summarized the results into six sections: Tools for prediction of life expectancy (before treatment), Tools for prediction of pathological stage (before treatment), Tools for prediction of survival and cancer-specific mortality (before/after treatment), Tools for prediction of biochemical recurrence (before/after treatment), Tools for prediction of metastatic progression (after treatment) and in the last section biomarkers and genomics. The management of PCa patients requires a tailored approach to deliver a truly personalized treatment. The currently available tools are of great help in helping the urologist in the decision-making process. These tests perform very well in high-grade and low-grade disease, while for intermediate-grade disease further research is needed. Newly discovered markers, genomic tests, and advances in imaging acquisition through mpMRI will help in instilling confidence that the appropriate treatments are being offered to patients with prostate cancer.

Evaluation of positive surgical margins in patients undergoing robot-assisted and open radical prostatectomy according to preoperative risk groups.

PubMed

Suardi, Nazareno; Dell'Oglio, Paolo; Gallina, Andrea; Gandaglia, Giorgio; Buffi, Nicolò; Moschini, Marco; Fossati, Nicola; Lughezzani, Giovanni; Karakiewicz, Pierre I; Freschi, Massimo; Lucianò, Roberta; Shariat, Shahrokh F; Guazzoni, Giorgio; Gaboardi, Franco; Montorsi, Francesco; Briganti, Alberto

2016-02-01

Recent studies showed that robot-assisted radical prostatectomy (RARP) represents an oncologically safe procedure in patients with prostate cancer (PCa), where the rate of positive surgical margins (PSMs) might be lower in patients treated with RARP as compared with that of those undergoing the open approach (open RP [ORP]). The aim of this study is to analyze the rate of PSMs according to preoperative risk groups in a large cohort of patients treated with RARP and ORP in a single institution with standardized surgical technique and pathological examination. We evaluated 6,194 consecutive patients with PCa undergoing either ORP (71.1%) or RARP (28.9%) between 1992 and 2014. Logistic regression analyses were used to test the association between type of surgery and PSMs in each preoperative risk group (low vs. intermediate vs. high) after adjusting for confounders. Overall, 21.6% patients had PSMs. RARP was associated with a lower rate of PSMs in low-risk (11.5 vs. 15.4%, P = 0.01), intermediate-risk (18.9 vs. 23.5%, P = 0.008), and high-risk patients (19.7 vs. 30.1%, P<0.001). In multivariable analyses, after stratification according to risk group categories, no difference in PSMs between RARP and ORP was observed for low-risk (odds ratio [OR] = 0.87, P = 0.46) and intermediate-risk patients (OR = 0.84, P = 0.19). Conversely, RARP was associated with lower odds of PSMs in high-risk patients (OR = 0.69, P = 0.04). Similar results were observed when our analyses were repeated after accounting for pathological characteristics, in patients treated between 2006 and 2014 and in a cohort of men treated by high-volume surgeons (all P≤ 0.03). The introduction of RARP at our institution led to a significant reduction in the risk of PSMs in patients with PCa with high-risk disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Dose painting to treat single-lobe prostate cancer with hypofractionated high-dose radiation using targeted external beam radiation: Is it feasible?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amini, Arya; Westerly, David C.; Waxweiler, Timothy V.

Targeted focal therapy strategies for treating single-lobe prostate cancer are under investigation. In this planning study, we investigate the feasibility of treating a portion of the prostate to full-dose external beam radiation with reduced dose to the opposite lobe, compared with full-dose radiation delivered to the entire gland using hypofractionated radiation. For 10 consecutive patients with low- to intermediate-risk prostate cancer, 2 hypofractionated, single-arc volumetric-modulated arc therapy (VMAT) plans were designed. The first plan (standard hypofractionation regimen [STD]) included the entire prostate gland, treated to 70 Gy delivered in 28 fractions. The second dose painting plan (DP) encompassed the involvedmore » lobe treated to 70 Gy delivered in 28 fractions, whereas the opposing, uninvolved lobe received 50.4 Gy in 28 fractions. Mean dose to the opposing neurovascular bundle (NVB) was considerably lower for DP vs STD, with a mean dose of 53.9 vs 72.3 Gy (p < 0.001). Mean penile bulb dose was 18.6 Gy for DP vs 19.2 Gy for STD (p = 0.880). Mean rectal dose was 21.0 Gy for DP vs 22.8 Gy for STD (p = 0.356). Rectum V{sub 70} (the volume receiving ≥70 Gy) was 2.01% for DP vs 2.74% for STD (p = 0.328). Bladder V{sub 70} was 1.69% for DP vs 2.78% for STD (p = 0.232). Planning target volume (PTV) maximum dose points were 76.5 and 76.3 Gy for DP and STD, respectively (p = 0.760). This study demonstrates the feasibility of using VMAT for partial-lobe prostate radiation in patients with prostate cancer involving 1 lobe. Partial-lobe prostate plans appeared to spare adjacent critical structures including the opposite NVB.« less

Application of Cu-64 NODAGA-PSMA PET in Prostate Cancer.

PubMed

Sevcenco, Sabina; Klingler, Hans Christoph; Eredics, Klaus; Friedl, Alexander; Schneeweiss, Jenifer; Knoll, Peter; Kunit, Thomas; Lusuardi, Lukas; Mirzaei, Siroos

2018-06-01

The high diagnostic potential of 64 Cu-PSMA PET-CT imaging was clinically investigated in prostate cancer patients with recurrent disease and in the primary staging of selected patients with advanced local disease. The aim of our study is to assess the uptake behavior in the clinical setting of 64Copper Prostate-Specific Membrane Antigen ( 64 Cu PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) in prostate cancer. A retrospective study was performed in 23 patients with intermediate, high risk and progressive disease at primary staging of prostate cancer. All patients underwent 64 Cu-PSMA PET. Overall, 250 MBq (4 MBq per kg bodyweight, range 230-290 MBq) of 64 Cu-NODAGA PSMA was intravenously applied. PET images were performed 30 min (pelvis and abdomen) and 1-2 h post-injection (skull base to mid-thigh). Maximum standardized uptake values (SUVmax) were measured in the organs with high physiological uptake such as liver and kidney, and, additionally, background activity was measured in the gluteal area and in suspected tumor lesions using a HERMES workstation. PSMA uptake was detected in prostate bed in nine patients, in six patients in distant metastases (bone, lung and liver) and in nine patients in lymph nodes. Of 23 patients, 5 (20.8%) did not show any focal pathological uptake in the whole body. The number of sites (prostate bed, lymph nodes, distant metastases) with positive PSMA uptake was significantly associated with PSA values before imaging (P = 0.0032). The 64 Cu PSMA uptake increased significantly from 30 min to 1-3 h post-injection (Wilcoxon signed rank test, P = 0.002). 64 Cu NODAGA-PSMA PET is a promising imaging tool in the detection of residual disease in patients with recurrent or primary progressive prostate cancer. Furthermore, the increased tracer uptake over time indicates in vivo stability of the diagnostic radiopharmaceutical.

Potential impact of 68Ga-PSMA-11 PET/CT on prostate cancer definitive radiation therapy planning.

PubMed

Calais, Jérémie; Kishan, Amar U; Cao, Minsong; Fendler, Wolfgang P; Eiber, Matthias; Herrmann, Ken; Ceci, Francesco; Reiter, Robert E; Rettig, Matthew B; Hegde, John V; Shaverdian, Narek; King, Christopher R; Steinberg, Michael L; Czernin, Johannes; Nickols, Nicholas G

2018-04-13

Background: Standard-of-care imaging for initial staging of prostate cancer (PCa) underestimates disease burden. Prostate specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) detects PCa metastasis with superior accuracy with potential impact definitive radiation therapy (RT) planning for non-metastatic PCa. Objectives: i) To determine how often definitive PCa RT planning based on standard target volumes cover 68 Ga-PSMA-11 PET/CT defined disease, and ii) To assess the potential impact of 68 Ga-PSMA-11 PET/CT on definitive PCa RT planning. Patients and Methods: This is a post-hoc analysis of an intention to treat population of 73 patients with localized PCa without prior local therapy who underwent 68 Ga-PSMA PET/CT for initial staging as part of an Investigational New Drug trial. 11/73 were intermediate-risk (15%), 33/73 were high-risk (45%), 22/73 were very high risk (30%), and 7/73 were N1 (9.5%). Clinical target volumes (CTVs) that included the prostate, seminal vesicles, and pelvic lymph nodes (LNs) using Radiation Therapy Oncology Group (RTOG) consensus guidelines were contoured on the CT portion of the PET/CT by a radiation oncologist blinded to the PET findings. 68 Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. PSMA-positive lesions not covered by planning volumes based on the CTVs were considered to have a major potential impact on treatment planning. Results: All patients had PSMA-positive primary prostate lesion(s). 25/73 (34%) and 7/73 (9.5%) had PSMA-positive pelvic nodal and distant metastases, respectively. The sites of nodal metastases in decreasing order of frequency were external iliac (20.5%), common iliac (13.5%), internal iliac (12.5%) obturator (12.5%), perirectal (4%), abdominal (4%), upper-diaphragm (4%), and presacral (1.5%). The median size of the nodal lesions was 6 mm (range 4-24 mm). RT planning based on the CTVs covered 69/73 (94.5%) of primary disease and 20/25 (80%) of pelvic nodal disease, on a per-patient analysis. Conclusion: 68 Ga-PSMA-11 PET/CT had a major impact on intended definitive PCa RT planning in 12/73 of patients (16.5%) when RT fields covered the prostate, seminal vesicles and the pelvic LNs, and in 25/66 of patients (37%) when RT fields covered only the prostate and seminal vesicles (without pelvic LNs). Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

External-Beam Radiation Therapy and High-Dose Rate Brachytherapy Combined With Long-Term Androgen Deprivation Therapy in High and Very High Prostate Cancer: Preliminary Data on Clinical Outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez-Monge, Rafael, E-mail: rmartinezm@unav.es; Moreno, Marta; Ciervide, Raquel

2012-03-01

Purpose: To determine the feasibility of combined long-term androgen deprivation therapy (ADT) and dose escalation with high-dose-rate (HDR) brachytherapy. Methods and Materials: Between 2001 and 2007, 200 patients with high-risk prostate cancer (32.5%) or very high-risk prostate cancer (67.5%) were prospectively enrolled in this Phase II trial. Tumor characteristics included a median pretreatment prostate-specific antigen of 15.2 ng/mL, a clinical stage of T2c, and a Gleason score of 7. Treatment consisted of 54 Gy of external irradiation (three-dimensional conformal radiotherapy [3DCRT]) followed by 19 Gy of HDR brachytherapy in four twice-daily treatments. ADT started 0-3 months before 3DCRT and continuedmore » for 2 years. Results: One hundred and ninety patients (95%) received 2 years of ADT. After a median follow-up of 3.7 years (range, 2-9), late Grade {>=}2 urinary toxicity was observed in 18% of the patients and Grade {>=}3 was observed in 5%. Prior transurethral resection of the prostate (p = 0.013) and bladder D{sub 50} {>=}1.19 Gy (p = 0.014) were associated with increased Grade {>=}2 urinary complications; age {>=}70 (p = 0.05) was associated with Grade {>=}3 urinary complications. Late Grade {>=}2 gastrointestinal toxicity was observed in 9% of the patients and Grade {>=}3 in 1.5%. CTV size {>=}35.8 cc (p = 0.007) and D{sub 100} {>=}3.05 Gy (p = 0.01) were significant for increased Grade {>=}2 complications. The 5-year and 9-year biochemical relapse-free survival (nadir + 2) rates were 85.1% and 75.7%, respectively. Patients with Gleason score of 7-10 had a decreased biochemical relapse-free survival (p = 0.007). Conclusions: Intermediate-term results at the 5-year time point indicate a favorable outcome without an increase in the rate of late complications.« less

Comparison of Biochemical Relapse-Free Survival Between Primary Gleason Score 3 and Primary Gleason Score 4 for Biopsy Gleason Score 7 Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burdick, Michael J.; Reddy, Chandana A.; Ulchaker, James

2009-04-01

Purpose: To determine whether the primary grade (PG) of biopsy Gleason score (GS) 7 prostate cancer (CaP) was predictive for biochemical relapse-free survival (bRFS). Most of the present data regarding the PG of GS7 CaP refer to surgical specimens. Our goal was to determine whether the biopsy GS used at the time of medical decision making predicted for the biochemical outcome. Methods and Materials: We reviewed the data from 705 patients with biopsy GS7 CaP, from a prospectively maintained database, who had been treated at our institution between September 1996 and March 2005 with radical prostatectomy (n = 310), externalmore » beam radiotherapy (n = 268), or prostate radioactive seed implantation (n = 127). The bRFS rates were estimated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used for univariate and multivariate analyses examining these factors in relation to bRFS: PG of biopsy GS, initial prostate-specific antigen level, clinical T stage, use of androgen deprivation, risk group (high or intermediate), and treatment modality. Results: The 5-year bRFS rate was 78% and 71% (p = 0.0108) for biopsy GS7 PG3 CaP and biopsy GS7 PG4 CaP, respectively. Comparing PG3 and PG4 within treatment modalities, only prostate implantation patients had a significant difference in the 5-year bRFS rate, 88% vs. 76%, respectively (p = 0.0231). On multivariate analysis, the PG of biopsy GS remained an independent predictor of bRFS, with PG3 having better bRFS than PG4 (relative risk, 0.655; 95% confidence interval, 0.472-0.909; p = 0.0113). Conclusion: Biopsy GS7 PG4 CaP carries a worse bRFS than biopsy GS7 PG3 CaP.« less

High b Value (2,000 s/mm2) Diffusion-Weighted Magnetic Resonance Imaging in Prostate Cancer at 3 Tesla: Comparison with 1,000 s/mm2 for Tumor Conspicuity and Discrimination of Aggressiveness

PubMed Central

Tamada, Tsutomu; Kanomata, Naoki; Sone, Teruki; Jo, Yoshimasa; Miyaji, Yoshiyuki; Higashi, Hiroki; Yamamoto, Akira; Ito, Katsuyoshi

2014-01-01

Objective The objective of our study was to investigate tumor conspicuity and the discrimination potential for tumor aggressiveness on diffusion-weighted magnetic resonance imaging (DW-MRI) with high b value at 3-T. Materials and Methods The institutional review board approved this study and waived the requirement for informed consent. A total of 50 patients with prostate cancer (69 cancer foci; 48 in the PZ, 20 in the TZ, and one in whole prostate) who underwent multiparametric prostate MRI including DW-MRI (b values: 0, 1000 s/mm2 and 0, 2000 s/mm2) on a 3-T system were included. Lesion conspicuity score (LCS) using visual assessment (1 = invisible for surrounding normal site; 2 = slightly high intensity; 3 = moderately high; and 4 = very high) and tumor-normal signal intensity ratio (TNR) were assessed, and apparent diffusion coefficient (ADC, ×10−3 mm2/s) of the tumor regions and normal regions were measured. Results Mean LCS and TNR at 0, 2000 s/mm2 was significantly higher than those at 0, 1000 s/mm2 (p<0.001 for both). In addition, ADC at both 0, 1000 and 0, 2000 s/mm2 was found to distinguish intermediate or high risk cancer with Gleason score ≥7 from low risk cancer with Gleason score ≤6 (p<0.001 for both). Furthermore, ADC of tumor regions correlated with Gleason score at both 0, 1000 s/mm2 (ρ = −0.602; p<0.001) and 0, 2000 s/mm2 (ρ = −0.645; p<0.001). Conclusions For tumor conspicuity and characterization of prostate cancer on DW-MRI of 3-T MRI, b = 0, 2000 s/mm2 is more useful than b = 0, 1000 s/mm2. PMID:24802652

High b value (2,000 s/mm2) diffusion-weighted magnetic resonance imaging in prostate cancer at 3 Tesla: comparison with 1,000 s/mm2 for tumor conspicuity and discrimination of aggressiveness.

PubMed

Tamada, Tsutomu; Kanomata, Naoki; Sone, Teruki; Jo, Yoshimasa; Miyaji, Yoshiyuki; Higashi, Hiroki; Yamamoto, Akira; Ito, Katsuyoshi

2014-01-01

The objective of our study was to investigate tumor conspicuity and the discrimination potential for tumor aggressiveness on diffusion-weighted magnetic resonance imaging (DW-MRI) with high b value at 3-T. The institutional review board approved this study and waived the requirement for informed consent. A total of 50 patients with prostate cancer (69 cancer foci; 48 in the PZ, 20 in the TZ, and one in whole prostate) who underwent multiparametric prostate MRI including DW-MRI (b values: 0, 1000 s/mm2 and 0, 2000 s/mm2) on a 3-T system were included. Lesion conspicuity score (LCS) using visual assessment (1 = invisible for surrounding normal site; 2 = slightly high intensity; 3 = moderately high; and 4 = very high) and tumor-normal signal intensity ratio (TNR) were assessed, and apparent diffusion coefficient (ADC, ×10-3 mm2/s) of the tumor regions and normal regions were measured. Mean LCS and TNR at 0, 2000 s/mm2 was significantly higher than those at 0, 1000 s/mm2 (p<0.001 for both). In addition, ADC at both 0, 1000 and 0, 2000 s/mm2 was found to distinguish intermediate or high risk cancer with Gleason score ≥7 from low risk cancer with Gleason score ≤6 (p<0.001 for both). Furthermore, ADC of tumor regions correlated with Gleason score at both 0, 1000 s/mm2 (ρ = -0.602; p<0.001) and 0, 2000 s/mm2 (ρ = -0.645; p<0.001). For tumor conspicuity and characterization of prostate cancer on DW-MRI of 3-T MRI, b = 0, 2000 s/mm2 is more useful than b = 0, 1000 s/mm2.

Finasteride Concentrations and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial

PubMed Central

Till, Cathee; Goodman, Phyllis J.; Chen, Xiaohong; Leach, Robin J.; Johnson-Pais, Teresa L.; Hsing, Ann W.; Hoque, Ashraful; Tangen, Catherine M.; Chu, Lisa; Parnes, Howard L.; Schenk, Jeannette M.; Reichardt, Juergen K. V.; Thompson, Ian M.; Figg, William D.

2015-01-01

Objective In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying drug concentrations. Methods Data for this nested case-control study are from the PCPT. Cases were drawn from men with biopsy-proven prostate cancer and matched controls. Finasteride concentrations were measured using a liquid chromatography-mass spectrometry validated assay. The association of serum finasteride concentrations with prostate cancer risk was determined by logistic regression. We also examine whether polymorphisms in the enzyme target and metabolism genes of finasteride are related to drug concentrations using linear regression. Results and Conclusions Among men with detectable finasteride concentrations, there was no association between finasteride concentrations and prostate cancer risk, low-grade or high-grade, when finasteride concentration was analyzed as a continuous variable or categorized by cutoff points. Since there was no concentration-dependent effect on prostate cancer, any exposure to finasteride intake may reduce prostate cancer risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910), and CYP3A5 (rs15524; rs776746) were significantly associated with modifying finasteride concentrations. These results suggest that finasteride exposure may reduce prostate cancer risk and finasteride concentrations are affected by genetic variations in genes responsible for altering its metabolism pathway. Trial Registration ClinicalTrials.gov NCT00288106 PMID:25955319

Evaluating genetic risk for prostate cancer among Japanese and Latinos

PubMed Central

Cheng, Iona; Chen, Gary K.; Nakagawa, Hidewaki; He, Jing; Wan, Peggy; Laurie, Cathy; Shen, Jess; Sheng, Xin; Pooler, Loreall C.; Crenshaw, Andrew T.; Mirel, Daniel B.; Takahashi, Atsushi; Kubo, Michiaki; Nakamura, Yusuke; Al Olama, Ali Amin; Benlloch, Sara; Donovan, Jenny L.; Guy, Michelle; Hamdy, Freddie C.; Kote-Jarai, Zsofia; Neal, David E.; Wilkens, Lynne R.; Monroe, Kristine R.; Stram, Daniel O.; Muir, Kenneth; Eeles, Rosalind A.; Easton, Douglas F.; Kolonel, Laurence N.; Henderson, Brian E.; Le Marchand, Loïc; Haiman, Christopher A.

2012-01-01

Background There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Methods Our first stage GWAS of prostate cancer included Japanese (cases/controls=1,033/1,042) and Latino (cases/controls=1,043/1,057) from the Multiethnic Cohort. Significant associations from stage 1 (P < 1.0×10−4) were examined in silico in GWAS of prostate cancer (stage 2) in Japanese (cases/controls=1,583/3,386) and Europeans (cases/controls=1,854/1,894). Results No novel stage 1 SNPs outside of known risk regions reached genome-wide significance. For Japanese, in stage 1, the most notable putative novel association was seen with 10 SNPs (P<8.0. x10−6) at chromosome 2q33; however, this was not replicated in stage 2. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage 1: OR=1.45; P=7.01×10−5 and stage 2: OR=1.58; P =3.05×10−7). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele=1.10; P = 2.71×10−25 and OR=1.07; P = 1.02×10−16 for Japanese and Latinos, respectively). Conclusion and Impact Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings demonstrate that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos. PMID:22923026

Evaluating genetic risk for prostate cancer among Japanese and Latinos.

PubMed

Cheng, Iona; Chen, Gary K; Nakagawa, Hidewaki; He, Jing; Wan, Peggy; Laurie, Cathy C; Shen, Jess; Sheng, Xin; Pooler, Loreall C; Crenshaw, Andrew T; Mirel, Daniel B; Takahashi, Atsushi; Kubo, Michiaki; Nakamura, Yusuke; Al Olama, Ali Amin; Benlloch, Sara; Donovan, Jenny L; Guy, Michelle; Hamdy, Freddie C; Kote-Jarai, Zsofia; Neal, David E; Wilkens, Lynne R; Monroe, Kristine R; Stram, Daniel O; Muir, Kenneth; Eeles, Rosalind A; Easton, Douglas F; Kolonel, Laurence N; Henderson, Brian E; Le Marchand, Loïc; Haiman, Christopher A

2012-11-01

There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Our first-stage GWAS of prostate cancer included Japanese (cases/controls = 1,033/1,042) and Latino (cases/controls = 1,043/1,057) from the Multiethnic Cohort (MEC). Significant associations from stage I (P < 1.0 × 10(-4)) were examined in silico in GWAS of prostate cancer (stage II) in Japanese (cases/controls = 1,583/3,386) and Europeans (cases/controls = 1,854/1,894). No novel stage I single-nucleotide polymorphism (SNP) outside of known risk regions reached genome-wide significance. For Japanese, in stage I, the most notable putative novel association was seen with 10 SNPs (P ≤ 8.0 × 10(-6)) at chromosome 2q33; however, this was not replicated in stage II. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage I: OR = 1.45; P = 7.01 × 10(-5) and stage II: OR = 1.58; P = 3.05 × 10(-7)). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele = 1.10; P = 2.71 × 10(-25) and OR = 1.07; P = 1.02 × 10(-16) for Japanese and Latinos, respectively). Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings show that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos. ©2012 AACR.

Roles for the Stem Cell–Associated Intermediate Filament Nestin in Prostate Cancer Migration and Metastasis

PubMed Central

Kleeberger, Wolfram; Bova, G. Steven; Nielsen, Matthew E.; Herawi, Mehsati; Chuang, Ai-Ying; Epstein, Jonathan I.; Berman, David M.

2011-01-01

The intermediate filament protein Nestin identifies stem/progenitor cells in adult tissues, but the function of Nestin is poorly understood. We investigated Nestin expression and function in common lethal cancers. Nestin mRNA was detected in cell lines from small cell lung, and breast cancers, and particularly elevated in cell lines derived from prostate cancer metastases. Whereas the androgen-independent lines PC3, 22RV1, and DU145 all expressed Nestin transcripts under standard culture conditions, the androgen-dependent line LnCaP expressed Nestin only on androgen withdrawal. We confirmed associations of Nestin expression, androgen withdrawal, and metastatic potential by immunohistochemical analysis of samples from 254 prostate cancer patients. Cytoplasmic Nestin protein was readily identifiable in prostate cancer cells from 75% of patients with lethal androgen-independent disease, even in cancer sampled from the prostate itself. However, Nestin expression was undetectable in localized androgen-deprived tumors and in metastases without prior androgen deprivation. To address its function, we reduced Nestin levels with short hairpin RNAs, markedly inhibiting in vitro migration and invasion in prostate cancer cells but leaving cell growth intact. Nestin knockdown also diminished metastases 5-fold compared with controls despite uncompromised tumorigenicity at the site of inoculation. These results specify a function for Nestin in cell motility and identify a novel pathway for prostate cancer metastasis. Activity of this pathway may be selected by the extraprostatic environment or, as supported by our data, may originate within the prostate after androgen deprivation. Further dissection of this novel Nestin migration pathway may lead to strategies to prevent and neutralize metastatic spread. PMID:17909025

Urinary prostate-specific antigen: predictor of benign prostatic hyperplasia progression?

PubMed

Pejcic, Tomislav P; Tulic, Cane Dz; Lalic, Natasa V; Glisic, Biljana D; Ignjatovic, Svetlana D; Markovic, Biljana B; Hadzi-Djokic, Jovan B

2013-04-01

Urinary prostate-specific antigen (uPSA) can be used as additional parameter of benign prostatic hyperplasia (BPH) progression. From January 2001 to December 2011, uPSA was determined in 265 patients with benign prostate. Based on total prostate volume (TPV), the patients with benign prostate were divided in two groups: TPV < 31 mL and TPV ≥ 31 mL. Additional three groups were formed upon MTOPS study criteria: non- progressive BPH group (TPV < 31 mL, PSA < 1.6 ng/mL, age < 62 yrs), intermediate group (one, or two parameters {TPV, PSA, age} increased) and progressive BPH group (TPV ≥ 31 ml, PSA ≥ 1.6 ng/mL, age ≥ 62 yrs). Average uPSA values in the groups TPV < 31 mL and TPV ≥ 31 mL were 119.3 ± 124.5 and 255.5 ± 204.9 ng/mL, respectively and they were significantly different (p < 0.0001). Average uPSA values in the non- progressive BPH group, intermediate group and progressive BPH group were 86.8 ± 82.4 ng/mL, 166.6 ± 164.9 ng/mL and 274.9 ± 208.3 ng/mL, respectively and they were significantly different (p < 0.0001). The level of uPSA correlated significantly with TPV (r = 0.32, p < 0.0001). The cut off uPSA level of 150 ng/mL discriminates the patients with non-progressive BPH and progressive BPH with specificity of 0.83 and sensitivity of 0.67. The level of uPSA reflects prostatic hormonal activity and correlates with TPV, PSA and age. UPSA level ≥ 150 ng/mL can be used as additional predictive parameter of BPH progression.

Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study.

PubMed

Jamnagerwalla, Juzar; Howard, Lauren E; Allott, Emma H; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freeman, Michael R; Freedland, Stephen J

2017-12-27

Epidemiologic evidence for a serum cholesterol-prostate cancer link is mixed. Prostate-specific antigen (PSA) is positively correlated with cholesterol, potentially increasing PSA-driven biopsy recommendations in men with high cholesterol, though biopsy compliance may be lower in men with comorbid conditions. These potential biases may affect PSA-driven biopsy rates and subsequent prostate cancer detection in men with high serum cholesterol. Our objective was to test the association between serum cholesterol and prostate cancer risk in men receiving PSA independent, study-mandated prostate biopsies. We conducted a post hoc analysis of data from 4974 non-statin users in REDUCE, a randomized trial in men with elevated PSA and a negative baseline biopsy. Men underwent 2- and 4-year trial-mandated prostate biopsies. Associations between baseline serum levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and prostate cancer risk, overall and by Gleason grade (<7 vs. ≥7), were examined using multivariable logistic regression. High total serum cholesterol was associated with an increased risk of high-grade prostate cancer diagnosis (OR per 10 mg/dL 1.05; 95% CI 1.00-1.09; p = 0.048), but cholesterol was unrelated to either overall or low-grade prostate cancer risk (p-values >0.185). There was no association between serum LDL and overall, low- or high-grade prostate cancer risk (p-values >0.137). In contrast, elevated serum HDL was associated with increased risk of both overall (OR per 10 mg/dL 1.08; 95% CI 1.01-1.16; p = 0.033) and high-grade prostate cancer (OR per 10 mg/dL 1.14; 95% CI 1.01-1.28; p = 0.034). In REDUCE, where all men received PSA independent, trial-mandated biopsies thus ensuring complete prostate cancer ascertainment, high total serum cholesterol and high HDL were associated with increased risk of high-grade prostate cancer, supporting a cholesterol-prostate cancer link.

Lessons Learned from Implementing a Prostate Cancer Risk Assessment Program for Underserved High-Risk Men in the Community: the Prostate REACH Project.

PubMed

Fleisher, Linda; Davis, Stacy N; Gross, Laura; Bagden, Loretta; Zakrzewski, Debra; González, Evelyn; Kandadai, Venk; Rusten, Cheryl; Baskett, Jerilyn; Obeid, Elias; Giri, Veda N

2016-03-01

Prostate cancer disproportionately affects Black men, who may also encounter barriers to participation in prostate cancer risk assessment. The Prostate Risk, Education and Assessment in the Community with Help (REACH) project was a community-based extension of a comprehensive prostate cancer risk assessment program at a comprehensive cancer center. The goals of the REACH project were the following: (1) establish a community prostate cancer risk assessment clinic, (2) conduct targeted recruitment, and (3) provide navigation services including follow-up for uninsured men. Key implementation steps included the following: (1) choosing a clinic site, (2) establishing patient access procedures, (3) establishing navigator services, (4) developing subsidy fund use guidelines, and (5) designing recruitment and promotion. Through community-based promotion, 64 men inquired about the program and 26 (41 %) participated. Of those screened, 46 % had abnormal results, and 2 men were diagnosed with prostate cancer. Here, we describe a unique demonstration project to implement a comprehensive prostate cancer risk assessment program in an underserved Black community and describe successes and challenges to inform future efforts to promote access to underserved men.

[Prostate cancer: Quality assessment of clinical management in the Midi-Pyrenean region in 2011].

PubMed

Daubisse-Marliac, L; Lamy, S; Lunardi, P; Tollon, C; Thoulouzan, M; Latorzeff, I; Bauvin, E; Grosclaude, P

2017-02-01

Assessing the quality of the clinical management of prostate cancer in the Midi-Pyrenean region in 2011. The study population was randomly selected among new cases of prostate cancer presented in Multidisciplinary Team Meeting (MTM) in 2011. The indicators defined with the professionals have evaluated the quality of the diagnostic care, when treatment started and at the time of the MTM. Six hundred and thirty-three new patients were included (median age at diagnosis=69years, min: 48; max: 93). In diagnostic period, 92% of patients had a prostate biopsy. Performing a pelvic MRI, an abdomino-pelvic CT and bone scintigraphy concerned respectively 53%, 55% and 61% of intermediate or high-risk patients. The Gleason score, surgical margins and pathological stage were included in over 98% patient records treated by radical prostatectomy. A PSA assay in 3months after prostatectomy was found in 59% of surgical patients. The MTM was performed before treatment to 83% of patients. About three-quarters of surgical patients with stage pT≥3 or pN1 or with no healthy margins were discussed in MTM after surgery. Most of the studied indicators reach a high level. However, the lower level of realization of complementary examinations may question about their real place, accessibility and traceability. 4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Once-weekly versus every-other-day stereotactic body radiotherapy in patients with prostate cancer (PATRIOT): A phase 2 randomized trial.

PubMed

Quon, Harvey C; Ong, Aldrich; Cheung, Patrick; Chu, William; Chung, Hans T; Vesprini, Danny; Chowdhury, Amit; Panjwani, Dilip; Pang, Geordi; Korol, Renee; Davidson, Melanie; Ravi, Ananth; McCurdy, Boyd; Zhang, Liying; Mamedov, Alexandre; Deabreu, Andrea; Loblaw, Andrew

2018-05-01

Prostate stereotactic body radiotherapy (SBRT) regimens differ in time, dose, and fractionation. We completed a multicentre, randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL). Men with low and intermediate-risk prostate cancer were randomly assigned to 40 Gy in 5 fractions delivered once per week (QW) vs. every other day (EOD). QOL was assessed using the Expanded Prostate Cancer Index Composite. The primary endpoint was the proportion with a minimum clinically important change (MCIC) in bowel QOL during the acute (≤12 week) period, and analysis was by intention-to-treat. ClinicalTrials.gov NCT01423474. 152 men from 3 centres were randomized with median follow-up of 47 months. Patients treated QW had superior acute bowel QOL with 47/69 (68%) reporting a MCIC compared to 63/70 (90%) treated EOD (p = 0.002). Fewer patients treated QW reported moderate-severe problems with bowel QOL during the acute period compared with EOD (14/70 [20%] vs. 40/70 [57%], p < 0.001). Acute urinary QOL was also better in the QW arm, with 52/67 (78%) vs 65/69 (94%) experiencing a MCIC (p = 0.006). There were no significant differences in late urinary or bowel QOL at 2 years or last follow-up. Prostate SBRT delivered QW improved acute bowel and urinary QOL compared to EOD. Patients should be counselled regarding the potential for reduced short-term toxicity and improved QOL with QW prostate SBRT. Copyright © 2018 Elsevier B.V. All rights reserved.

PTV margin definition in hypofractionated IGRT of localized prostate cancer using cone beam CT and orthogonal image pairs with fiducial markers.

PubMed

Oehler, Christoph; Lang, Stephanie; Dimmerling, Peter; Bolesch, Christian; Kloeck, Stephan; Tini, Alessandra; Glanzmann, Christoph; Najafi, Yousef; Studer, Gabriela; Zwahlen, Daniel R

2014-11-11

To evaluate PTV margins for hypofractionated IGRT of prostate comparing kV/kV imaging or CBCT. Between 2009 and 2012, 20 patients with low- (LR), intermediate- (IR) and high-risk (HR) prostate cancer were treated with VMAT in supine position with fiducial markers (FM), endorectal balloon (ERB) and full bladder. CBCT's and kV/kV imaging were performed before and additional CBCT's after treatment assessing intra-fraction motion. CTVP for 5 patients with LR and CTVPSV for 5 patients with IR/HR prostate cancer were contoured independently by 3 radiation oncologists using MRI. The van Hark formula (PTV margin =2.5Σ +0.7σ) was applied to calculate PTV margins of prostate/seminal vesicles (P/PSV) using CBCT or FM. 172 and 52 CBCTs before and after RT and 507 kV/kV images before RT were analysed. Differences between FM in CBCT or in planar kV image pairs were below 1 mm. Accounting for both random and systematic uncertainties anisotropic PTV margins were 5-8 mm for P (LR) and 6-11 mm for PSV (IR/HR). Random uncertainties like intra-fraction and inter-fraction (setup) uncertainties were of similar magnitude (0.9-1.4 mm). Largest uncertainty was introduced by CTV delineation (LR: 1-2 mm, IR/HR: 1.6-3.5 mm). Patient positioning using bone matching or ERB-matching resulted in larger PTV margins. For IGRT CBCT or kV/kV-image pairs with FM are interchangeable in respect of accuracy. Especially for hypofractionated RT, PTV margins can be kept in the range of 5 mm or below if stringent daily IGRT, ideally including prostate tracking, is applied. MR-based CTV delineation optimization is recommended.

Clinical Utility of Quantitative Gleason Grading in Prostate Biopsies and Prostatectomy Specimens.

PubMed

Sauter, Guido; Steurer, Stefan; Clauditz, Till Sebastian; Krech, Till; Wittmer, Corinna; Lutz, Florian; Lennartz, Maximilian; Janssen, Tim; Hakimi, Nayira; Simon, Ronald; von Petersdorff-Campen, Mareike; Jacobsen, Frank; von Loga, Katharina; Wilczak, Waldemar; Minner, Sarah; Tsourlakis, Maria Christina; Chirico, Viktoria; Haese, Alexander; Heinzer, Hans; Beyer, Burkhard; Graefen, Markus; Michl, Uwe; Salomon, Georg; Steuber, Thomas; Budäus, Lars Henrik; Hekeler, Elena; Malsy-Mink, Julia; Kutzera, Sven; Fraune, Christoph; Göbel, Cosima; Huland, Hartwig; Schlomm, Thorsten

2016-04-01

Gleason grading is the strongest prognostic parameter in prostate cancer. Gleason grading is categorized as Gleason ≤ 6, 3 + 4, 4 + 3, 8, and 9-10, but there is variability within these subgroups. For example, Gleason 4 components may range from 5-45% in a Gleason 3 + 4 = 7 cancer. To assess the clinical relevance of the fractions of Gleason patterns. Prostatectomy specimens from 12823 consecutive patients and of 2971 matched preoperative biopsies for which clinical data with an annual follow-up between 2005 and 2014 were available from the Martini-Klinik database. To evaluate the utility of quantitative grading, the fraction of Gleason 3, 4, and 5 patterns seen in biopsies and prostatectomies were recorded. Gleason grade fractions were compared with prostatectomy findings and prostate-specific antigen recurrence. Our data suggest a striking utility of quantitative Gleason grading. In prostatectomy specimens, there was a continuous increase of the risk of prostate-specific antigen recurrence with increasing percentage of Gleason 4 fractions with remarkably small differences in outcome at clinically important thresholds (0% vs 5%; 40% vs 60% Gleason 4), distinguishing traditionally established prognostic groups. Also, in biopsies, the quantitative Gleason scoring identified various intermediate risk groups with respect to Gleason findings in corresponding prostatectomies. Quantitative grading may also reduce the clinical impact of interobserver variability because borderline findings such as tumors with 5%, 40%, or 60% Gleason 4 fractions and very small Gleason 5 fractions (with pivotal impact on the Gleason score) are disclaimed. Quantitative Gleason pattern data should routinely be provided in addition to Gleason score categories, both in biopsies and in prostatectomy specimens. Gleason score is the most important prognostic parameter in prostate cancer, but prone to interobserver variation. The results of our study show that morphological aspects that define the Gleason grade in prostate cancer represent a continuum. Quantitation of Gleason patterns provides clinically relevant information beyond the traditional Gleason grading categories ≤ 3 + 3, 3 + 4, 4 + 3, 8, 9 -1 0. Quantitative Gleason scoring can help to minimize variations between different pathologists and substantially aid in optimized therapy decision-making. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

SU-E-T-457: Impact of Interfractional Variations On Anterior Vs. Lateral-Field Proton Therapy of Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moteabbed, M; Trofimov, A; Sharp, G C

2015-06-15

Purpose: To investigate the effects of interfractional anatomy and setup variations on plans with anterior-oblique vs. lateral beams for prostate cancer pencil beam scanning (PBS) and passive scattered (PS) proton therapy. Methods: Six patients with low/intermediate risk prostate cancer treated with PS proton therapy at our institution were selected. All patients underwent weekly verification CT scans. Implanted fiducials were used for localization, and endorectal balloons for prostate immobilization. New PBS plans with lateral beams, as well as PBS and PS plans with anterior-oblique beams (±35 deg) were created. PBS plans used two different spot sizes: ∼10mm (large) and ∼5mm (medium)more » sigma at 25cm range and optimized as single-field-uniform-dose with ∼8% non-uniformity. No range uncertainty margins were applied in PBS plans to maximize rectal sparing. Field-specific apertures were used when planning with large spots to sharpen the penumbrae. The planned dose was recomputed on each weekly CT with fiducials aligned to the simulation CT, scaled and accumulated via deformable image registration. Results: The dose volume analysis showed that although difference between planned and accumulated dose remains negligible for plans with conventional lateral beams using both PS and PBS, this is not the case for plans with anterior beams. The target coverage in anterior plans was largely degraded due to the variations in the beam path length and the absence of range margins. The average prostate D95 was reduced by 7.5/15.9% (using PS/PBS) after accumulation for anterior plans, compared with 0/0.4% for lateral plans. The average mean dose in organs-at-risk decreased by 1% for lateral and 2% for anterior plans, similarly for PS and PBS. Spot size did not affect the dose changes. Conclusion: Prostate plans using anterior beams may undergo clinically relevant interfractional dose degradation. Corrective strategies guided by in-vivo range measurements should be studied before clinical application of this technique.« less

Men’s health supplement use and outcomes in men receiving definitive intensity-modulated radiation therapy for localized prostate cancer123

PubMed Central

Churilla, Thomas M; Ruth, Karen; Hayes, Shelly B; Sobczak, Mark L; Hallman, Mark A; Smaldone, Marc C; Chen, David YT; Horwitz, Eric M

2016-01-01

Background: Approximately 50% of newly diagnosed cancer patients start taking dietary supplements. Men’s health supplements (MHSs), which we define as supplements that are specifically marketed with the terms men’s health and prostate health (or similar permutations), are often mislabeled as having potential anticancer benefits. Objective: We evaluated the effects of MHSs on patient outcomes and toxicities in patients who were undergoing definitive intensity-modulated radiation therapy (IMRT) for localized prostate cancer. Design: This retrospective analysis included patients who were being treated at a National Cancer Institute–designated comprehensive cancer center and consented to have information stored in a prospective database. MHSs were queried online. Outcome measures were freedom from biochemical failure (FFBF) (biochemical failure was defined with the use of the prostate-specific antigen nadir + 2-ng/mL definition), freedom from distant metastasis (FFDM), cancer-specific survival (CSS), and overall survival (OS) as well as toxicities. Kaplan-Meier analysis, log-rank tests, Fine and Gray competing-risk regression (to adjust for patient and lifestyle factors), and Cox models were used. Results: From 2001 to 2012, 2207 patients were treated with IMRT with a median dose of 78 Gy, and a median follow-up of 46 mo. Of these patients, 43% were low risk, 37% were intermediate risk, and 20% were high risk; 10% used MHSs. MHSs contained a median of 3 identifiable ingredients (range: 0–78 ingredients). Patients who were taking an MHS compared with those who were not had improved 5-y OS (97% compared with 92%, respectively; P = 0.01), but there were no differences in the FFBF (94% compared with 89%, respectively; P = 0.12), FFDM (96% compared with 97%, respectively; P = 0.32), or CSS (100% compared with 99%, respectively; P = 0.22). The unadjusted association between MHS use and improved OS was attenuated after adjustment for patient lifestyle factors and comorbidities. There was no difference in toxicities between the 2 groups (late-grade 3–4 genitourinary <3%; gastrointestinal <4%). Conclusion: The use of MHSs is not associated with outcomes or toxicities. PMID:27797706

Vasectomy and prostate cancer risk: a historical synopsis of undulating false causality.

PubMed

Nutt, Max; Reed, Zachary; Köhler, Tobias S

2016-01-01

The potential influence of vasectomy being a risk factor for the development of prostate cancer is not a new concept, with more than 30 publications addressing the topic. Given the global frequency of vasectomy and the prevalence of prostate cancer, this subject justifiably deserves scrutiny. Several articles have claimed that vasectomy puts men at risk for future development of prostate cancer. We explore articles that have shown the contrary (no link), explore the studies' strengths and weaknesses, describe possible prostate cancer pathophysiologic mechanisms, and apply Bradford Hill criteria to help discern correlation with causation. The risk and interest of association of prostate cancer with vasectomy has waxed and waned over the last three decades. Based on our review, vasectomy remains a safe form of sterilization and does not increase prostate cancer risk.

Choline intake and risk of lethal prostate cancer: incidence and survival123

PubMed Central

Richman, Erin L; Kenfield, Stacey A; Stampfer, Meir J; Giovannucci, Edward L; Zeisel, Steven H; Willett, Walter C; Chan, June M

2012-01-01

Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer. PMID:22952174

Height, selected genetic markers and prostate cancer risk: results from the PRACTICAL consortium.

PubMed

Lophatananon, Artitaya; Stewart-Brown, Sarah; Kote-Jarai, Zsofia; Olama, Ali Amin Al; Garcia, Sara Benlloch; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Giles, Graham G; Fitzgerald, Liesel M; Southey, Melissa C; Pharoah, Paul; Pashayan, Nora; Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus; Stanford, Janet L; Brenner, Hermann; Dieffenbach, Aida K; Arndt, Volker; Park, Jong Y; Lin, Hui-Yi; Sellers, Thomas; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Spurdle, Amanda; Clements, Judith A; Easton, Douglas; Eeles, Rosalind A; Muir, Kenneth

2017-08-22

Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. The results suggest that height is associated with high-grade prostate cancer risk. Men with height >180 cm are at a 22% increased risk as compared to men with height <173 cm (OR 1.22, 95% CI 1.01-1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. There was no evidence of gene-environment interaction between height and the selected candidate SNPs.Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.

Association of genetic and non-genetic risk factors with the development of prostate cancer in Malaysian men.

PubMed

Munretnam, Khamsigan; Alex, Livy; Ramzi, Nurul Hanis; Chahil, Jagdish Kaur; Kavitha, I S; Hashim, Nikman Adli Nor; Lye, Say Hean; Velapasamy, Sharmila; Ler, Lian Wee

2014-01-01

There is growing global interest to stratify men into different levels of risk to developing prostate cancer, thus it is important to identify common genetic variants that confer the risk. Although many studies have identified more than a dozen common genetic variants which are highly associated with prostate cancer, none have been done in Malaysian population. To determine the association of such variants in Malaysian men with prostate cancer, we evaluated a panel of 768 SNPs found previously associated with various cancers which also included the prostate specific SNPs in a population based case control study (51 case subjects with prostate cancer and 51 control subjects) in Malaysian men of Malay, Chinese and Indian ethnicity. We identified 21 SNPs significantly associated with prostate cancer. Among these, 12 SNPs were strongly associated with increased risk of prostate cancer while remaining nine SNPs were associated with reduced risk. However, data analysis based on ethnic stratification led to only five SNPs in Malays and 3 SNPs in Chinese which remained significant. This could be due to small sample size in each ethnic group. Significant non-genetic risk factors were also identified for their association with prostate cancer. Our study is the first to investigate the involvement of multiple variants towards susceptibility for PC in Malaysian men using genotyping approach. Identified SNPs and non-genetic risk factors have a significant association with prostate cancer.

Prostate cancer progression and mortality: a review of diet and lifestyle factors.

PubMed

Peisch, Sam F; Van Blarigan, Erin L; Chan, June M; Stampfer, Meir J; Kenfield, Stacey A

2017-06-01

To review and summarize evidence on the role of diet and lifestyle factors and prostate cancer progression, with a specific focus on habits after diagnosis and the risk of subsequent disease recurrence, progression, or death. Given the well-documented heterogeneity of prostate cancer and the long survivorship of the majority of diagnoses, our goal was to summarize and describe modifiable risk factors for clinically relevant prostate cancer. We focused where possible on epidemiologic studies of post-diagnostic habits and prostate cancer progression, defined as recurrence (e.g., PSA risk, secondary treatment), metastasis, or death. Where data were limited, we also describe evidence on risk factors and indicators of prostate cancer aggressiveness at diagnosis. A variety of dietary and lifestyle factors appear to affect prostate cancer progression. Several generally widely recommended lifestyle factors such as not smoking, maintaining a healthy body weight, and regular vigorous physical exercise also appear to affect prostate cancer progression. Several dietary factors, such as tomato sauce/lycopene, cruciferous vegetables, healthy sources of vegetable fats, and coffee, may also have a role in reducing risk of prostate cancer progression. Diet and lifestyle factors, in particular exercise and smoking cessation, may reduce the risk of prostate cancer progression and death. These promising findings warrant further investigation, as their overall impact might be large.

ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodda, Sree; Tyldesley, Scott; Department of Surgery, University of British Columbia, Vancouver, British Columbia

Purpose: To report the genitourinary (GU) and gastrointestinal (GI) morbidity and erectile dysfunction in a randomized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer. Methods and Materials: ASCENDE-RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) enrolled 398 men, median age 68 years, who were then randomized to either a standard arm that included 12 months of androgen deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. At clinic visits, investigators recorded GUmore » and GI morbidity and information on urinary continence, catheter use, and erectile function. Exclusion of 15 who received nonprotocol treatment and correction of 14 crossover events left 195 men who actually received a DE-EBRT boost and 188, an LDR-PB boost. Median follow-up was 6.5 years. Results: The LDR-PB boost increased the risk of needing temporary catheterization and/or requiring incontinence pads. At 5 years the cumulative incidence of grade 3 GU events was 18.4% for LDR-PB, versus 5.2% for DE-EBRT (P<.001). Compared with the cumulative incidence, the 5-year prevalence of grade 3 GU morbidity was substantially lower for both arms (8.6% vs 2.2%, P=.058). The 5-year cumulative incidence of grade 3 GI events was 8.1% for LDR-PB, versus 3.2% for DE-EBRT (P=.124). The 5-year prevalence of grade 3 GI toxicity was lower than the cumulative incidence for both arms (1.0% vs 2.2%, respectively). Among men reporting adequate baseline erections, 45% of LDR-PB patients reported similar erectile function at 5 years, versus 37% after DE-EBRT (P=.30). Conclusions: The incidence of acute and late GU morbidity was higher after LDR-PB boost, and there was a nonsignificant trend for worse GI morbidity. No differences in the frequency of erectile dysfunction were observed.« less

Occupational risk factors for prostate cancer in an area of former coal, iron, and steel industries in Germany. Part 1: Results from a study performed in the 1980s.

PubMed

Dickhut, Silvia; Urfer, Wolfgang; Reich, Susanne; Bandel, Tiemo; Bremicker, Karl-Dieter; Neugebauer, Wolfgang; Sökeland, Jürgen; Bolt, Hermann M; Golka, Klaus

2016-01-01

Prostate cancer is the most frequent occurring malignancy in men in many Western countries. Unfortunately, only a few studies on occupational risk factors have been published. Thus, the aim of this study was to investigate possible occupational risk factors in a former center of coal, iron, and steel industries the greater Dortmund area, located in the western part of Germany. In three local departments of urology, a total of 238 prostate cancer cases and 414 patients with benign prostatic hyperplasia as controls were requested to provide information for all jobs ever performed for 6 mo or longer. Jobs performed less than 10 yr prior to diagnosis were excluded from the analysis due to the latency of prostate cancer. In addition, data on smoking habits and age were obtained. Analysis of data was performed by means of logistic regression. Hard coal miners and, based on fewer cases, painters, stratified by age, showed a significantly elevated prostate cancer risk. Smoking history did not influence prostate cancer risk. The causes of the observed increased prostate cancer risk in hard coal miners cannot be explained by merely the risk factor "male sexual hormones." In former decades, underground hard coal miners were exposed to high concentrations of dust and different xenobiotics such as hydraulic oils. Surprisingly, in a study performed about a decade later in the same area, prostate cancer risk in underground hard coal miners was found to be reduced. However, exposure to colorants was associated with an increased prostate cancer risk.

Biases in Recommendations for and Acceptance of Prostate Biopsy Significantly Affect Assessment of Prostate Cancer Risk Factors: Results From Two Large Randomized Clinical Trials

PubMed Central

Goodman, Phyllis J.; Till, Cathee; Schenk, Jeannette M.; Lucia, M. Scott; Thompson, Ian M.

2016-01-01

Purpose To identify factors related to who undergoes a prostate biopsy in a screened population and to estimate the impact of biopsy verification on risk factor–prostate cancer associations. Patients and Methods Men who were screened regularly from the placebo arms of two large prostate cancer prevention trials (Prostate Cancer Prevention Trial [PCPT] and Selenium and Vitamin E Cancer Prevention Trial [SELECT]) were examined to define incident prostate cancer cohorts. Because PCPT had an end-of-study biopsy, prostate cancer cases were categorized by a preceding prostate-specific antigen/digital rectal examination prompt (yes/no) and noncases by biopsy-proven negative status (yes v no). We estimated the association of risk factors (age, ethnicity, family history, body mass index, medication use) with prostate cancer and quantified differences in risk associations across cohorts. Results Men 60 to 69 years of age, those with benign prostatic hyperplasia, and those with a family history of prostate cancer were more likely, and those with a higher body mass index (≥ 25), diabetes, or a smoking history were less likely, to undergo biopsy, adjusting for age and longitudinal prostate-specific antigen and digital rectal examination. Medication use, education, and marital status also influenced who underwent biopsy. Some risk factor estimates for prostate cancer varied substantially across cohorts. Black (v other ethnicities) had odds ratios (ORs) that varied from 1.20 for SELECT (community screening standards, epidemiologic-like cohort) to 1.83 for PCPT (end-of-study biopsy supplemented with imputed end points). Statin use in SELECT provided an OR of 0.65 and statin use in in PCPT provided an OR of 0.99, a relative difference of 34%. Conclusion Among screened men enrolled in prostate cancer prevention trials, differences in risk factor estimates for prostate cancer likely underestimate the magnitude of bias found in other cohorts with varying screening and biopsy recommendations and acceptance. Risk factors for prostate cancer derived from epidemiologic studies not only may be erroneous but may lead to misdirected research efforts. PMID:27998216

Inflammation on Prostate Needle Biopsy is Associated with Lower Prostate Cancer Risk: A Meta-Analysis.

PubMed

Vasavada, Shaleen R; Dobbs, Ryan W; Kajdacsy-Balla, André A; Abern, Michael R; Moreira, Daniel M

2018-05-01

We performed a comprehensive literature review and meta-analysis to evaluate the association of inflammation on prostate needle biopsies and prostate cancer risk. We searched Embase®, PubMed® and Web of Science™ from January 1, 1990 to October 1, 2016 for abstracts containing the key words prostate cancer, inflammation and biopsy. Study inclusion criteria were original research, adult human subjects, cohort or case-control study design, histological inflammation on prostate needle biopsy and prostate cancer on histology. Two independent teams reviewed abstracts and extracted data from the selected manuscripts. Combined ORs and 95% CIs of any, acute and chronic inflammation were calculated using the random effects method. Of the 1,030 retrieved abstracts 46 underwent full text review and 25 were included in the final analysis, comprising a total of 20,585 subjects and 6,641 patients with prostate cancer. There was significant heterogeneity among studies (I 2 = 84.4%, p <0.001). The presence of any inflammation was significantly associated with a lower prostate cancer risk in 25 studies (OR 0.455, 95% CI 0.337-0.573). There was no evidence of publication bias (p >0.05). When subanalyzed by inflammation type, acute inflammation in 4 studies and chronic inflammation in 15 were each associated with a lower prostate cancer risk (OR 0.681, 95% CI 0.450-0.913 and OR 0.499, 95% CI 0.334-0.665, respectively). In a meta-analysis of 25 studies inflammation on prostate needle biopsy was associated with a lower prostate cancer risk. Clinically the presence of inflammation on prostate needle biopsy may lower the risk of a subsequent prostate cancer diagnosis. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate-cancer associated SNPs for familial disease

PubMed Central

Teerlink, Craig C.; Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.; Rinckleb, Antje; Maier, Christiane; Vogel, Walther; Cancel-Tassin, Geraldine; Egrot, Christophe; Cussenot, Olivier; Foulkes, William D.; Giles, Graham G.; Hopper, John L.; Severi, Gianluca; Eeles, Ros; Easton, Douglas; Kote-Jarai, Zsofia; Guy, Michelle; Cooney, Kathleen A.; Ray, Anna M.; Zuhlke, Kimberly A.; Lange, Ethan M.; FitzGerald, Liesel M.; Stanford, Janet L.; Ostrander, Elaine A.; Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Isaacs, William B.; Wahlfors, Tiina; Tammela, Teuvo; Schleutker, Johanna; Wiklund, Fredrik; Grönberg, Henrik; Emanuelsson, Monica; Carpten, John; Bailey-Wilson, Joan; Whittemore, Alice S.; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin; Catalona, William J.; Zheng, S. Lilly; Jin, Guangfu; Lu, Lingyi; Xu, Jianfeng; Camp, Nicola J.; Cannon-Albright, Lisa A.

2013-01-01

Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p≤1E−3) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may be contribute risk to aggressive disease. PMID:24162621

Replication of prostate cancer risk loci in a Japanese case-control association study.

PubMed

Yamada, Hiroki; Penney, Kathryn L; Takahashi, Hiroyuki; Katoh, Takahiko; Yamano, Yuko; Yamakado, Minoru; Kimura, Takahiro; Kuruma, Hidetoshi; Kamata, Yuko; Egawa, Shin; Freedman, Matthew L

2009-10-07

Two prostate cancer genome-wide scans in populations of European ancestry identified several genetic variants that are strongly associated with prostate cancer risk. The effect of these risk variants and their cumulative effect in other populations are unknown. We evaluated the association of 23 risk single-nucleotide polymorphisms (SNPs) with prostate cancer risk and clinical covariates (Gleason score, tumor aggressiveness, and age at diagnosis) in men of Japanese ancestry (311 case subjects and 1035 control subjects) using unconditional logistic regression. We also used logistic regression to test the association between increasing numbers of independently associated risk alleles and the risk of prostate cancer, prostate cancer aggressiveness, and age at diagnosis. All statistical tests were two-sided. Seven of the 23 SNPs (five independent loci) were associated with prostate cancer risk (P values ranged from .0084 to 2.3 x 10(-8) and effect sizes [estimated as odds ratios, ORs] ranged from 1.35 to 1.82). None of the seven SNPs was associated with Gleason score or aggressive disease. rs6983561 and rs4430796 were associated with age at diagnosis (Ps = .0188 and .0339, respectively). Men with six or more risk alleles (27% of case patients and 11% of control subjects) had a higher risk of prostate cancer than men with two or fewer risk alleles (7% of case patients and 20% of control subjects) (OR = 6.22, P = 1.5 x 10(-12)). These results highlight the critical importance of considering ancestry in understanding how risk alleles influence disease and suggest that risk estimates and variants differ across populations. It is important to perform studies in multiple ancestral populations so that the composite genetic architecture of prostate cancer can be rigorously addressed.

Impact of a clinical trial initiative on clinical trial enrollment in a multidisciplinary prostate cancer clinic.

PubMed

Madsen, Lydia T; Kuban, Deborah A; Choi, Seungtaek; Davis, John W; Kim, Jeri; Lee, Andrew K; Domain, Delora; Levy, Larry; Pisters, Louis L; Pettaway, Curtis A; Ward, John F; Logothetis, Christopher; Hoffman, Karen E

2014-07-01

Clinical oncology trials are hampered by low accrual rates, with fewer than 5% of adult patients with cancer treated on study. Clinical trial enrollment was evaluated at The University of Texas MD Anderson Cancer Center's Multidisciplinary Prostate Cancer Clinic (MPCC) to assess whether a clinical trial initiative, introduced in 2006, impacted enrollment. The trial initiative included posting trial-specific information in clinic, educating patients about appropriate clinical trial options during the treatment recommendation discussion, and providing patients with trial-specific educational information. The investigators evaluated the frequency of clinical trial enrollment for men with newly diagnosed prostate cancer seen in the MPCC from 2004 to 2008. Logistic regression evaluated the impact of patient characteristics and the clinical trial initiative on trial enrollment. The median age of the 1370 men was 64 years; 32% had low-risk, 49% had intermediate-risk, and 19% had high-risk disease. Overall, 74% enrolled in at least one trial and 29% enrolled in more than one trial. Trial enrollment increased from 39% before the initiative (127/326) to 84% (880/1044) after the trial initiative. Patient enrollment increased in laboratory studies (from 25% to 80%), quality-of-life studies (from 10% to 26%), and studies evaluating investigational treatments and systemic agents (from 6% to 15%) after the trial initiative. In multivariate analysis, younger men (P<.001) and men seen after implementation of the clinical trial initiative (P<.001) were more likely to enroll in trials. Clinical trial enrollment in the MPCC was substantially higher than that seen nationally in adult patients with cancer, and enrollment rates increased after the introduction of a clinical trial initiative. Copyright © 2014 by the National Comprehensive Cancer Network.

Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr; EMR3738, Université Lyon 1, Lyon; Decullier, Evelyne

Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Eventsmore » version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.« less

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial.

PubMed

Chin, Joseph L; Billia, Michele; Relle, James; Roethke, Matthias C; Popeneciu, Ionel V; Kuru, Timur H; Hatiboglu, Gencay; Mueller-Wolf, Maya B; Motsch, Johann; Romagnoli, Cesare; Kassam, Zahra; Harle, Christopher C; Hafron, Jason; Nandalur, Kiran R; Chronik, Blaine A; Burtnyk, Mathieu; Schlemmer, Heinz-Peter; Pahernik, Sascha

2016-09-01

Magnetic resonance imaging-guided transurethral ultrasound ablation (MRI-TULSA) is a novel minimally invasive technology for ablating prostate tissue, potentially offering good disease control of localized cancer and low morbidity. To determine the clinical safety and feasibility of MRI-TULSA for whole-gland prostate ablation in a primary treatment setting of localized prostate cancer (PCa). A single-arm prospective phase 1 study was performed at three tertiary referral centers in Canada, Germany, and the United States. Thirty patients (median age: 69 yr; interquartile range [IQR]: 67-71 yr) with biopsy-proven low-risk (80%) and intermediate-risk (20%) PCa were treated and followed for 12 mo. MRI-TULSA treatment was delivered with the therapeutic intent of conservative whole-gland ablation including 3-mm safety margins and 10% residual viable prostate expected around the capsule. Primary end points were safety (adverse events) and feasibility (technical accuracy and precision of conformal thermal ablation). Exploratory outcomes included quality of life, prostate-specific antigen (PSA), and biopsy at 12 mo. Median treatment time was 36min (IQR: 26-44) and prostate volume was 44ml (IQR: 38-48). Spatial control of thermal ablation was ±1.3mm on MRI thermometry. Common Terminology Criteria for Adverse Events included hematuria (43% grade [G] 1; 6.7% G2), urinary tract infections (33% G2), acute urinary retention (10% G1; 17% G2), and epididymitis (3.3% G3). There were no rectal injuries. Median pretreatment International Prostate Symptom Score 8 (IQR: 5-13) returned to 6 (IQR: 4-10) at 3 mo (mean change: -2; 95% confidence interval [CI], -4 to 1). Median pretreatment International Index of Erectile Function 13 (IQR: 6-28) recovered to 13 (IQR: 5-25) at 12 mo (mean change: -1; 95% CI, -5 to 3). Median PSA decreased 87% at 1 mo and was stable at 0.8 ng/ml (IQR: 0.6-1.1) to 12 mo. Positive biopsies showed 61% reduction in total cancer length, clinically significant disease in 9 of 29 patients (31%; 95% CI, 15-51), and any disease in 16 of 29 patients (55%; 95% CI, 36-74). MRI-TULSA was feasible, safe, and technically precise for whole-gland prostate ablation in patients with localized PCa. Phase 1 data are sufficiently compelling to study MRI-TULSA further in a larger prospective trial with reduced safety margins. We used magnetic resonance imaging-guided transurethral ultrasound to heat and ablate the prostate in men with prostate cancer. We showed that the treatment can be targeted within a narrow range (1mm) and has a well-tolerated side effect profile. A larger study is under way. NCT01686958, DRKS00005311. Copyright © 2016. Published by Elsevier B.V.

Functional Recovery, Oncologic Outcomes and Postoperative Complications after Robot-Assisted Radical Prostatectomy: An Evidence-Based Analysis Comparing the Retzius Sparing and Standard Approaches.

PubMed

Menon, Mani; Dalela, Deepansh; Jamil, Marcus; Diaz, Mireya; Tallman, Christopher; Abdollah, Firas; Sood, Akshay; Lehtola, Linda; Miller, David; Jeong, Wooju

2018-05-01

We report a 1-year update of functional urinary and sexual recovery, oncologic outcomes and postoperative complications in patients who completed a randomized controlled trial comparing posterior (Retzius sparing) with anterior robot-assisted radical prostatectomy. A total of 120 patients with clinically low-intermediate risk prostate cancer were randomized to undergo robot-assisted radical prostatectomy via the posterior and anterior approach in 60 each. Surgery was performed by a single surgical team at an academic institution. An independent third party ascertained urinary and sexual function outcomes preoperatively, and 3, 6 and 12 months after surgery. Oncologic outcomes consisted of positive surgical margins and biochemical recurrence-free survival. Biochemical recurrence was defined as 2 postoperative prostate specific antigen values of 0.2 ng/ml or greater. Median age of the cohort was 61 years and median followup was 12 months. At 12 months in the anterior vs posterior prostatectomy groups there were no statistically significant differences in the urinary continence rate (0 to 1 security pad per day in 93.3% vs 98.3%, p = 0.09), 24-hour pad weight (median 12 vs 7.5 gm, p = 0.3), erection sufficient for intercourse (69.2% vs 86.5%) or postoperative Sexual Health Inventory for Men score 17 or greater (44.6% vs 44.1%). In the posterior vs anterior prostatectomy groups a nonfocal positive surgical margin was found in 11.7% vs 8.3%, biochemical recurrence-free survival probability was 0.84 vs 0.93 and postoperative complications developed in 18.3% vs 11.7%. Among patients with clinically low-intermediate risk prostate cancer randomized to anterior (Menon) or posterior (Bocciardi) approach robot-assisted radical prostatectomy the differences in urinary continence seen at 3 months were muted at the 12-month followup. Sexual function recovery, postoperative complication and biochemical recurrence rates were comparable 1 year postoperatively. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

HDR brachytherapy of prostate cancer – two years experience in Greater Poland Cancer Centre

PubMed Central

Skowronek, Janusz; Chicheł, Adam

2009-01-01

Purpose The aim of this work was to analyze the results and complications of three treatment schemes of patients with initially localized prostate cancer after two years of observation time. Material and methods Sixty-three patients were enrolled into the study and divided into groups according to radiation schemes (I group – EBRT 50 Gy/BRT 15 Gy, II – EBRT 46 Gy/BRT 2 × 10 Gy, III group – BRT 3 × 15 Gy). Group I, II and III consisted of 46 (73%), 14 (22.2%), 3 (4.8%) patients, respectively. The low-, intermediate- and high risk groups consisted of 23 (36.5%), 18 (28.5%) and 22 (35%) men, respectively. Results and tolerance of the treatment and acute complications in analyzed groups were discussed. Results Median observation time was 24 months. Complete remission was observed in 43 patients (68.3%) out of the whole group. Locoregional and distal metastases progression were noted in 4 patients (6.4%). Partial remission was observed in low-, intermediate- and high risk group: 7.9%, 9.5% and 9.5% of all men. Nadir of PSA results were estimated as mean value of 0.094 ng/ml, average 0.0-0.63. The mean value for the complete group decreased from 0.98 ng/ml (range 0.0-9.7) in the third months to 0.32 ng/ml after one year (0.0-3.34) of the end of treatment time. Urologic and gastrointenstinal side effects were noted in different rates according to 1 month observation (dysuria – 22.2%, urinary incontinence – 7.9%, frequency – 58.7%, weak stream – 68.3%, rectal bleeding – 15.9%). Conclusions 1. HDR brachytherapy of prostate cancer can be used as a boost after or before the external beam radiation therapy in different treatment schemes. 2. In selected groups under investigation trials, sole HDR-BRT is a suitable method of treatment. 3. To confirm superiority of analyzed modality treatment a prospective investigation with larger groups of patients would be required. PMID:27807455

Genetic variation in IL-16 miRNA target site and time to prostate cancer diagnosis in African American men

PubMed Central

Hughes, Lucinda; Ruth, Karen; Rebbeck, Timothy R.; Giri, Veda N.

2013-01-01

Background Men with a family history of prostate cancer and African American men are at high risk for prostate cancer and in need of personalized risk estimates to inform screening decisions. This study evaluated genetic variants in genes encoding microRNA (miRNA) binding sites for informing of time to prostate cancer diagnosis among ethnically-diverse, high-risk men undergoing prostate cancer screening. Methods The Prostate Cancer Risk Assessment Program (PRAP) is a longitudinal screening program for high-risk men. Eligibility includes men ages 35-69 with a family history of prostate cancer or African descent. Participants with ≥ 1 follow-up visit were included in the analyses (n=477). Genetic variants in regions encoding miRNA binding sites in four target genes (ALOX15, IL-16, IL-18, and RAF1) previously implicated in prostate cancer development were evaluated. Genotyping methods included Taqman® SNP Genotyping Assay (Applied Biosystems) or pyrosequencing. Cox models were used to assess time to prostate cancer diagnosis by risk genotype. Results Among 256 African Americans with ≥ one follow-up visit, the TT genotype at rs1131445 in IL-16 was significantly associated with earlier time to prostate cancer diagnosis vs. the CC/CT genotypes (p=0.013), with a suggestive association after correction for false-discovery (p=0.065). Hazard ratio after controlling for age and PSA for TT vs. CC/CT among African Americans was 3.0 (95% CI 1.26-7.12). No association to time to diagnosis was detected among Caucasians by IL-16 genotype. No association to time to prostate cancer diagnosis was found for the other miRNA target genotypes. Conclusions Genetic variation in IL-16 encoding miRNA target site may be informative of time to prostate cancer diagnosis among African American men enrolled in prostate cancer risk assessment, which may inform individualized prostate cancer screening strategies in the future. PMID:24061634

Prostate cancer-specific mortality and the extent of therapy in healthy elderly men with high-risk prostate cancer.

PubMed

Hoffman, Karen E; Chen, Ming-Hui; Moran, Brian J; Braccioforte, Michelle H; Dosoretz, Daniel; Salenius, Sharon; Katin, Michael J; Ross, Rudi; D'Amico, Anthony V

2010-06-01

The risk of prostate cancer-specific mortality (PCSM) in healthy elderly men may depend on extent of treatment. The authors of this report compared the use of brachytherapy alone with combined brachytherapy, external-beam radiation to the prostate and seminal vesicles, and androgen-suppression therapy (CMT) in this population. The study cohort comprised 764 men aged > or = 65 years with high-risk prostate cancer (T3 or T4N0M0, prostate-specific antigen >20 ng/mL, and/or Gleason score 8-10) who received either brachytherapy alone (n = 206) or CMT (n = 558) at the Chicago Prostate Cancer Center or at a 21st Century Oncology facility. Men either had no history of myocardial infarction (MI) or had a history of MI treated with a stent or surgical intervention. Fine and Gray regression analysis was used to identify the factors associated with PCSM. The median patient age was 73 years (interquartile range, 70-77 years). After a median follow-up of 4.9 years, 25 men died of prostate cancer. After adjusting for age and prostate cancer prognostic factors, the risk of PCSM was significantly less (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12-0.68; P = .004) for men who received CMT than for men who received brachytherapy alone. Other factors that were associated significantly with an increased risk of PCSM included a Gleason score of 8 to 10 (P = .017). Elderly men who had high-risk prostate cancer without cardiovascular disease or with surgically corrected cardiovascular disease had a lower risk of PCSM when they received CMT than when they received brachytherapy alone. These results support aggressive locoregional treatment in healthy elderly men with high-risk prostate cancer. (c) 2010 American Cancer Society.

Vegetable and fruit intake after diagnosis and risk of prostate cancer progression.

PubMed

Richman, Erin L; Carroll, Peter R; Chan, June M

2012-07-01

Cruciferous vegetables, tomato sauce and legumes have been associated with reduced risk of incident advanced prostate cancer. In vitro and animal studies suggest these foods may inhibit progression of prostate cancer, but there are limited data in men. Therefore, we prospectively examined whether intake of total vegetables, and specifically cruciferous vegetables, tomato sauce and legumes, after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, a United States prostate cancer registry. As a secondary analysis, we also examined other vegetable subgroups, total fruit and subgroups of fruits. The participants were diagnosed primarily at community-based clinics and followed from 2004 to 2009. We assessed vegetable and fruit intake via a semi-quantitative food frequency questionnaire, and ascertained prostate cancer outcomes via urologist report and medical records. We observed 134 events of progression (53 biochemical recurrences, 71 secondary treatments likely due to recurrence, 6 bone metastases and 4 prostate cancer deaths) during 3,171 person-years. Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59% decreased risk of prostate cancer progression compared to men in the lowest quartile (hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.22, 0.76; p-trend: 0.003). No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression. In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression. Copyright © 2011 UICC.

Tailored community cancer education programs: Pawsox and prostates.

PubMed

Glicksman, Arvin S; Meyer, Andrea; Dipiero, Maureen

2010-06-01

To assess the prostate cancer screening practices in Rhode Island, we designed a questionnaire which was sent to 150 primary care physicians. A population-based survey was distributed to 194 men over 40 asking about screening history and risk factors. Eighty-five percent of primary care physicians reported performing annual prostate-specific antigen tests (PSAs) and digital rectal exams, 63% recognized family history as a risk factor, and 14% identified African Americans as a high-risk population. The survey found that 48% of men recognized family history as a risk factor and 6% understood that African Americans were at high risk. Each year, 200 men, primarily SED, are invited to a PawSox baseball game where physicians provide information on prostate cancer risk, treatment options, and outcomes. Free PSAs are provided. The questionnaire and survey demonstrate a need for more public education regarding prostate cancer in high-risk populations. Tailored community-based interventions, such as the Pawsox & Prostate program, can be effective professional and public education strategies to increase screening in high-risk populations.

Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate Cancer: A Meta-analysis

PubMed Central

Yang, Lin; Xie, Shuanghua; Feng, Xiaoshuang; Chen, Yuheng; Zheng, Tongzhang; Dai, Min; Ke Zhou, Cindy; Hu, Zhibin; Li, Ni; Hang, Dong

2015-01-01

Despite the increasing number of studies conducted recently to evaluate the association between HPV infections and the risk of prostate cancer, the results remain inconclusive. Furthermore, the prevalence and distribution of overall and individual HPV types worldwide in prostate cancer has not been reported until now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling data of 46 studies with 4919 prostate cancer cases, taking into account the heterogeneity of major related parameters, including study region, specimen type, HPV DNA source, detection method, publication calendar period and Gleason score. Moreover, we tested the association of HPV infections with prostate cancer risks by a meta-analysis of 26 tissue-based case-control studies. We found that the prevalence of HPV infection was 18.93% (95% CI = 17.84–20.05%) in prostate cancer cases, and most of which were high-risk HPV types (17.73%, 95% CI = 16.52–18.99%). The prevalence varied by region, PCR primers used, publication calendar period and Gleason score. Our study also showed a significantly increased risk of prostate cancer with the positivity of overall HPV detected in prostate tissues (OR = 1.79, 95% CI = 1.29–2.49) and revealed the geographic variation of association strength (P < 0.001). In conclusion, HPV infections may contribute to the risk of prostate cancer. PMID:26441160

Development and external multicenter validation of Chinese Prostate Cancer Consortium prostate cancer risk calculator for initial prostate biopsy.

PubMed

Chen, Rui; Xie, Liping; Xue, Wei; Ye, Zhangqun; Ma, Lulin; Gao, Xu; Ren, Shancheng; Wang, Fubo; Zhao, Lin; Xu, Chuanliang; Sun, Yinghao

2016-09-01

Substantial differences exist in the relationship of prostate cancer (PCa) detection rate and prostate-specific antigen (PSA) level between Western and Asian populations. Classic Western risk calculators, European Randomized Study for Screening of Prostate Cancer Risk Calculator, and Prostate Cancer Prevention Trial Risk Calculator, were shown to be not applicable in Asian populations. We aimed to develop and validate a risk calculator for predicting the probability of PCa and high-grade PCa (defined as Gleason Score sum 7 or higher) at initial prostate biopsy in Chinese men. Urology outpatients who underwent initial prostate biopsy according to the inclusion criteria were included. The multivariate logistic regression-based Chinese Prostate Cancer Consortium Risk Calculator (CPCC-RC) was constructed with cases from 2 hospitals in Shanghai. Discriminative ability, calibration and decision curve analysis were externally validated in 3 CPCC member hospitals. Of the 1,835 patients involved, PCa was identified in 338/924 (36.6%) and 294/911 (32.3%) men in the development and validation cohort, respectively. Multivariate logistic regression analyses showed that 5 predictors (age, logPSA, logPV, free PSA ratio, and digital rectal examination) were associated with PCa (Model 1) or high-grade PCa (Model 2), respectively. The area under the curve of Model 1 and Model 2 was 0.801 (95% CI: 0.771-0.831) and 0.826 (95% CI: 0.796-0.857), respectively. Both models illustrated good calibration and substantial improvement in decision curve analyses than any single predictors at all threshold probabilities. Higher predicting accuracy, better calibration, and greater clinical benefit were achieved by CPCC-RC, compared with European Randomized Study for Screening of Prostate Cancer Risk Calculator and Prostate Cancer Prevention Trial Risk Calculator in predicting PCa. CPCC-RC performed well in discrimination and calibration and decision curve analysis in external validation compared with Western risk calculators. CPCC-RC may aid in decision-making of prostate biopsy in Chinese or in other Asian populations with similar genetic and environmental backgrounds. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array

PubMed Central

Eeles, Rosalind A; Olama, Ali Amin Al; Benlloch, Sara; Saunders, Edward J; Leongamornlert, Daniel A; Tymrakiewicz, Malgorzata; Ghoussaini, Maya; Luccarini, Craig; Dennis, Joe; Jugurnauth-Little, Sarah; Dadaev, Tokhir; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Muir, Ken; Giles, Graham G; Severi, Gianluca; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schumacher, Fredrick; Henderson, Brian; Le Marchand, Loic; Lindstrom, Sara; Kraft, Peter; Hunter, David J; Gapstur, Susan; Chanock, Stephen J; Berndt, Sonja I; Albanes, Demetrius; Andriole, Gerald; Schleutker, Johanna; Weischer, Maren; Canzian, Federico; Riboli, Elio; Key, Tim J; Travis, Ruth; Campa, Daniele; Ingles, Sue A; John, Esther M; Hayes, Richard B; Pharoah, Paul DP; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet; Ostrander, Elaine A; Signorello, Lisa B; Thibodeau, Stephen N; Schaid, Dan; Maier, Christiane; Vogel, Walther; Kibel, Adam S; Cybulski, Cezary; Lubinski, Jan; Cannon-Albright; Brenner, Hermann; Park, Jong Y; Kaneva, Radka; Batra, Jyotsna; Spurdle, Amanda B; Clements, Judith A; Teixeira, Manuel R; Dicks, Ed; Lee, Andrew; Dunning, Alison; Baynes, Caroline; Conroy, Don; Maranian, Melanie J; Ahmed, Shahana; Govindasami, Koveela; Guy, Michelle; Wilkinson, Rosemary A; Sawyer, Emma J; Morgan, Angela; Dearnaley, David P; Horwich, Alan; Huddart, Robert A; Khoo, Vincent S; Parker, Christopher C; Van As, Nicholas J; Woodhouse, J; Thompson, Alan; Dudderidge, Tim; Ogden, Chris; Cooper, Colin; Lophatananon, Artitaya; Cox, Angela; Southey, Melissa; Hopper, John L; English, Dallas R; Aly, Markus; Adolfsson, Jan; Xu, Jiangfeng; Zheng, Siqun; Yeager, Meredith; Kaaks, Rudolf; Diver, W Ryan; Gaudet, Mia M; Stern, Mariana; Corral, Roman; Joshi, Amit D; Shahabi, Ahva; Wahlfors, Tiina; Tammela, Teuvo J; Auvinen, Anssi; Virtamo, Jarmo; Klarskov, Peter; Nordestgaard, Børge G; Røder, Andreas; Nielsen, Sune F; Bojesen, Stig E; Siddiq, Afshan; FitzGerald, Liesel; Kolb, Suzanne; Kwon, Erika; Karyadi, Danielle; Blot, William J; Zheng, Wei; Cai, Qiuyin; McDonnell, Shannon K; Rinckleb, Antje; Drake, Bettina; Colditz, Graham; Wokolorczyk, Dominika; Stephenson, Robert A; Teerlink, Craig; Muller, Heiko; Rothenbacher, Dietrich; Sellers, Thomas A; Lin, Hui-Yi; Slavov, Chavdar; Mitev, Vanio; Lose, Felicity; Srinivasan, Srilakshmi; Maia, Sofia; Paulo, Paula; Lange, Ethan; Cooney, Kathleen A; Antoniou, Antonis; Vincent, Daniel; Bacot, François; Tessier; Kote-Jarai, Zsofia; Easton, Douglas F

2013-01-01

Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10−8). More than 70 prostate cancer susceptibility loci, explaining ~30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies. PMID:23535732

The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

PubMed

Whitaker, Hayley C; Kote-Jarai, Zsofia; Ross-Adams, Helen; Warren, Anne Y; Burge, Johanna; George, Anne; Bancroft, Elizabeth; Jhavar, Sameer; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Saunders, Edward; Page, Elizabeth; Mitra, Anita; Mitchell, Gillian; Lindeman, Geoffrey J; Evans, D Gareth; Blanco, Ignacio; Mercer, Catherine; Rubinstein, Wendy S; Clowes, Virginia; Douglas, Fiona; Hodgson, Shirley; Walker, Lisa; Donaldson, Alan; Izatt, Louise; Dorkins, Huw; Male, Alison; Tucker, Kathy; Stapleton, Alan; Lam, Jimmy; Kirk, Judy; Lilja, Hans; Easton, Douglas; Cooper, Colin; Eeles, Rosalind; Neal, David E

2010-10-13

Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk. MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate. These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

The rs10993994 Risk Allele for Prostate Cancer Results in Clinically Relevant Changes in Microseminoprotein-Beta Expression in Tissue and Urine

PubMed Central

Whitaker, Hayley C.; Warren, Anne Y.; Burge, Johanna; George, Anne; Bancroft, Elizabeth; Jhavar, Sameer; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Saunders, Edward; Page, Elizabeth; Mitra, Anita; Mitchell, Gillian; Lindeman, Geoffrey J.; Evans, D. Gareth; Blanco, Ignacio; Mercer, Catherine; Rubinstein, Wendy S.; Clowes, Virginia; Douglas, Fiona; Hodgson, Shirley; Walker, Lisa; Donaldson, Alan; Izatt, Louise; Dorkins, Huw; Male, Alison; Tucker, Kathy; Stapleton, Alan; Lam, Jimmy; Kirk, Judy; Lilja, Hans; Easton, Douglas; Cooper, Colin; Eeles, Rosalind; Neal, David E.

2010-01-01

Background Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk. Methodology/Principal Findings MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate. Conclusions These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring. PMID:20967219

Identifying in vivo DCE MRI markers associated with microvessel architecture and gleason grades of prostate cancer.

PubMed

Singanamalli, Asha; Rusu, Mirabela; Sparks, Rachel E; Shih, Natalie N C; Ziober, Amy; Wang, Li-Ping; Tomaszewski, John; Rosen, Mark; Feldman, Michael; Madabhushi, Anant

2016-01-01

To identify computer extracted in vivo dynamic contrast enhanced (DCE) MRI markers associated with quantitative histomorphometric (QH) characteristics of microvessels and Gleason scores (GS) in prostate cancer. This study considered retrospective data from 23 biopsy confirmed prostate cancer patients who underwent 3 Tesla multiparametric MRI before radical prostatectomy (RP). Representative slices from RP specimens were stained with vascular marker CD31. Tumor extent was mapped from RP sections onto DCE MRI using nonlinear registration methods. Seventy-seven microvessel QH features and 18 DCE MRI kinetic features were extracted and evaluated for their ability to distinguish low from intermediate and high GS. The effect of temporal sampling on kinetic features was assessed and correlations between those robust to temporal resolution and microvessel features discriminative of GS were examined. A total of 12 microvessel architectural features were discriminative of low and intermediate/high grade tumors with area under the receiver operating characteristic curve (AUC) > 0.7. These features were most highly correlated with mean washout gradient (WG) (max rho = -0.62). Independent analysis revealed WG to be moderately robust to temporal resolution (intraclass correlation coefficient [ICC] = 0.63) and WG variance, which was poorly correlated with microvessel features, to be predictive of low grade tumors (AUC = 0.77). Enhancement ratio was the most robust (ICC = 0.96) and discriminative (AUC = 0.78) kinetic feature but was moderately correlated with microvessel features (max rho = -0.52). Computer extracted features of prostate DCE MRI appear to be correlated with microvessel architecture and may be discriminative of low versus intermediate and high GS. © 2015 Wiley Periodicals, Inc.

Characterizing Genetic Risk at Known Prostate Cancer Susceptibility Loci in African Americans

PubMed Central

Haiman, Christopher A.; Chen, Gary K.; Blot, William J.; Strom, Sara S.; Berndt, Sonja I.; Kittles, Rick A.; Rybicki, Benjamin A.; Isaacs, William B.; Ingles, Sue A.; Stanford, Janet L.; Diver, W. Ryan; Witte, John S.; Chanock, Stephen J.; Kolb, Suzanne; Signorello, Lisa B.; Yamamura, Yuko; Neslund-Dudas, Christine; Thun, Michael J.; Murphy, Adam; Casey, Graham; Sheng, Xin; Wan, Peggy; Pooler, Loreall C.; Monroe, Kristine R.; Waters, Kevin M.; Le Marchand, Loic; Kolonel, Laurence N.; Stram, Daniel O.; Henderson, Brian E.

2011-01-01

GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p≤6×10−4) that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry. PMID:21637779

Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial

PubMed Central

James, Nicholas D; Sydes, Matthew R; Mason, Malcolm D; Clarke, Noel W; Anderson, John; Dearnaley, David P; Dwyer, John; Jovic, Gordana; Ritchie, Alastair WS; Russell, J Martin; Sanders, Karen; Thalmann, George N; Bertelli, Gianfilippo; Birtle, Alison J; O'Sullivan, Joe M; Protheroe, Andrew; Sheehan, Denise; Srihari, Narayanan; Parmar, Mahesh KB

2012-01-01

Summary Background Long-term hormone therapy alone is standard care for metastatic or high-risk, non-metastatic prostate cancer. STAMPEDE—an international, open-label, randomised controlled trial—uses a novel multiarm, multistage design to assess whether the early additional use of one or two drugs (docetaxel, zoledronic acid, celecoxib, zoledronic acid and docetaxel, or zoledronic acid and celecoxib) improves survival in men starting first-line, long-term hormone therapy. Here, we report the preplanned, second intermediate analysis comparing hormone therapy plus celecoxib (arm D) with hormone therapy alone (control arm A). Methods Eligible patients were men with newly diagnosed or rapidly relapsing prostate cancer who were starting long-term hormone therapy for the first time. Hormone therapy was given as standard care in all trial arms, with local radiotherapy encouraged for newly diagnosed patients without distant metastasis. Randomisation was done using minimisation with a random element across seven stratification factors. Patients randomly allocated to arm D received celecoxib 400 mg twice daily, given orally, until 1 year or disease progression (including prostate-specific antigen [PSA] failure). The intermediate outcome was failure-free survival (FFS) in three activity stages; the primary outcome was overall survival in a subsequent efficacy stage. Research arms were compared pairwise against the control arm on an intention-to-treat basis. Accrual of further patients was discontinued in any research arm showing safety concerns or insufficient evidence of activity (lack of benefit) compared with the control arm. The minimum targeted activity at the second intermediate activity stage was a hazard ratio (HR) of 0·92. This trial is registered with ClinicalTrials.gov, number NCT00268476, and with Current Controlled Trials, number ISRCTN78818544. Findings 2043 patients were enrolled in the trial from Oct 17, 2005, to Jan 31, 2011, of whom 584 were randomly allocated to receive hormone therapy alone (control group; arm A) and 291 to receive hormone therapy plus celecoxib (arm D). At the preplanned analysis of the second intermediate activity stage, with 305 FFS events (209 in arm A, 96 in arm D), there was no evidence of an advantage for hormone therapy plus celecoxib over hormone therapy alone: HR 0·98 (95% CI 0·90–1·06). 2-year FFS was 51% (95% CI 46–56) in arm A and 51% (95% CI 43–58) in arm D. There was no evidence of differences in the incidence of adverse events between groups (events of grade 3 or higher were noted at any time in 123 [23%, 95% CI 20–27] patients in arm A and 64 [25%, 19–30] in arm D). The most common grade 3–5 events adverse effects in both groups were endocrine disorders (55 [11%] of patients in arm A vs 19 [7%] in arm D) and musculoskeletal disorders (30 [6%] of patients in arm A vs 15 [6%] in arm D). The independent data monitoring committee recommended stopping accrual to both celecoxib-containing arms on grounds of lack of benefit and discontinuing celecoxib for patients currently on treatment, which was endorsed by the trial steering committee. Interpretation Celecoxib 400 mg twice daily for up to 1 year is insufficiently active in patients starting hormone therapy for high-risk prostate cancer, and we do not recommend its use in this setting. Accrual continues seamlessly to the other research arms and follow-up of all arms will continue to assess effects on overall survival. Funding Cancer Research UK, Pfizer, Novartis, Sanofi-Aventis, Medical Research Council (London, UK). PMID:22452894

Combining lymphovascular invasion with reactive stromal grade predicts prostate cancer mortality.

PubMed

Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

2016-09-01

Previous studies suggest that lymphovascular invasion (LVI) has a weak and variable effect on prognosis. It is uncertain whether LVI, determined by diagnostic prostate biopsy, predicts prostate cancer death. Data from experimental studies have indicated that carcinoma-associated fibroblasts in the reactive stroma could promote LVI and progression to metastasis. Thus, combining LVI with reactive stromal grade may identify prostate cancer patients at high risk of an unfavorable outcome. The purpose of the present study was to examine if LVI, determined by diagnostic biopsy, alone and in combination with reactive stromal grade could predict prostate cancer death. This population-based study included 283 patients with prostate cancer diagnosed by needle biopsy in Aust-Agder County (Norway) from 1991 to 1999. Clinical data were obtained by medical charts review. Two uropathologists evaluated LVI and reactive stromal grade. The endpoint was prostate cancer death. Patients with LVI had marginally higher risk of prostate cancer death compared to patients without LVI (hazard ratio: 1.8, P-value = 0.04). LVI had a stronger effect on prostate cancer death risk when a high reactive stromal grade was present (hazard ratio: 16.0, P-value <0.001). Therefore, patients with concomitant LVI and high reactive stromal grade were at particularly high risk for prostate cancer death. Evaluating LVI together with reactive stromal grade on diagnostic biopsies could be used to identify patients at high risk of death from prostate cancer. Prostate 76:1088-1094, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Prediction of individual genetic risk to prostate cancer using a polygenic score.

PubMed

Szulkin, Robert; Whitington, Thomas; Eklund, Martin; Aly, Markus; Eeles, Rosalind A; Easton, Douglas; Kote-Jarai, Z Sofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Southey, Melissa C; Fitzgerald, Liesel M; Henderson, Brian E; Schumacher, Fredrick; Haiman, Christopher A; Schleutker, Johanna; Wahlfors, Tiina; Tammela, Teuvo L J; Nordestgaard, Børge G; Key, Tim J; Travis, Ruth C; Neal, David E; Donovan, Jenny L; Hamdy, Freddie C; Pharoah, Paul; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; Maier, Christiane; Vogel, Walther; Luedeke, Manuel; Herkommer, Kathleen; Kibel, Adam S; Cybulski, Cezary; Lubiński, Jan; Kluźniak, Wojciech; Cannon-Albright, Lisa; Brenner, Hermann; Butterbach, Katja; Stegmaier, Christa; Park, Jong Y; Sellers, Thomas; Lin, Hui-Yi; Lim, Hui-Yi; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Clements, Judith A; Spurdle, Amanda; Teixeira, Manuel R; Paulo, Paula; Maia, Sofia; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej; Gronberg, Henrik; Wiklund, Fredrik

2015-09-01

Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction. © 2015 Wiley Periodicals, Inc.

Risks of Prostate Cancer Screening

MedlinePlus

... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... or routine screening test for prostate cancer. Screening tests for prostate cancer are under study, and there are screening clinical trials taking place ...

Alcohol consumption and PSA-detected prostate cancer risk—A case-control nested in the ProtecT study

PubMed Central

Zuccolo, Luisa; Lewis, Sarah J; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Smith, George Davey

2013-01-01

Alcohol is an established carcinogen but not an established risk factor for prostate cancer, despite some recent prospective studies suggesting increased risk among heavy drinkers. The aim of this study was to investigate the role of alcohol on prostate-specific antigen (PSA) levels and prostate cancer risk. Two thousand four hundred PSA detected prostate cancer cases and 12,700 controls matched on age and general practice were identified through a case-control study nested in the PSA-testing phase of a large UK-based randomized controlled trial for prostate cancer treatment (ProtecT). Linear and multinomial logistic regression models were used to estimate ratios of geometric means (RGMs) of PSA and relative risk ratios (RRRs) of prostate cancer by stage and grade, with 95% confidence intervals (CIs), associated with weekly alcohol intake and drinking patterns. We found evidence of lower PSA (RGM 0.98, 95% CI: 0.98–0.99) and decreased risk of low Gleason-grade (RRR 0.96; 95%CI 0.93–0.99) but increased risk of high-grade prostate cancer (RRR 1.04; 95%CI 0.99–1.08; pdifference=0.004) per 10 units/week increase in alcohol consumption, not explained by current BMI, blood pressure, comorbidities, or reverse causation. This is the first large population-based study to find evidence of lower PSA levels for increasing alcohol consumption, with potential public health implications for the detection of prostate cancer. Our results also support a modestly higher risk of high-grade disease for heavy drinkers, but require independent replication to establish the nature of the association of alcohol with low-grade disease, preferably in cohorts with a heterogeneous case-mix. What's new? Alcohol is not an established risk factor for prostate cancer; however, the current work suggests that heavy drinking could cause a small increase in risk of the more aggressive forms. If the results are confirmed to be causal, prostate cancer risk will be added to the many long-term health risks of heavy drinking, and public health strategies will then also reduce high-risk, poorer prognosis prostate cancer. The authors also found that heavy drinkers have lower PSA levels, suggesting that heavy alcohol consumption could be used as a marker to identify men in whom some cancers might be missed. PMID:23024014

Occupational risk factors for prostate cancer in an area of former coal, iron, and steel industries in Germany. Part 2: results from a study performed in the 1990s.

PubMed

Krech, Sabina; Selinski, Silvia; Bürger, Hannah; Hengstler, Jan G; Jedrusik, Peter; Hodzic, Jasmin; Knopf, H-Jürgen; Golka, Klaus

2016-01-01

Currently, there is no established occupational risk factor for prostate cancer. However, in the 1980s, a hospital-based case-control study in the greater Dortmund area showed an elevated risk for hard coal miners and, based on few cases, for painters and varnishers. Therefore, approximately 10 yr later, a similar study regarding prostate cancer was performed in this area. In total, 292 patients with prostate cancer who underwent radical prostatectomy and 313 controls who underwent transurethral resection of a benign prostatic hyperplasia were investigated by questionnaire. All of them were operated on between 1995 and 1999. This study showed a decreased risk for prostate cancer in hard coal miners (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.44-1.03). Occupational exposures related to an elevated risk for prostate cancer were exposures to combustion products (20% cases vs. 11% controls), colorants and dyes (19 vs. 13%), and cutting fluids (8 vs. 6%). The different prostate cancer risks for underground coal miners in two studies with a time interval of approximately 10 yr are striking. Factors to be discussed are the introduction of prostate-specific antigen (PSA) screening for prostate cancer and investigation of cases that underwent radical prostatectomy, where the disease in general is locally confined. Working conditions in the local underground coal mines improved over time but did not change markedly in the period of interest. In essence, the present study does not corroborate an elevated prostate cancer risk in former underground hard coal miners from the greater Dortmund area.

PSA-Based Screening Outcomes, Dietary Heterocyclic Amine Exposure, and Prostate Cancer Risk in African-Americans

DTIC Science & Technology

2006-01-01

associated micronutrients , and risk of prostate cancer. Epidemiol. Rev. 2001a: 23: 82-86. Chan J., and Giovannucci E. Dairy products, calcium, and...118. Chan J., and Giovannucci E. Vegetables, fruits, associated micronutrients , and risk of prostate cancer. Epidemiol. Rev. 2001a: 23: 82-86...Chan J., and Giovannucci E. Dairy products, calcium, and vitamin D, and risk of prostate cancer. Epidemiol. Rev. 2001b: 23: 87-92. Cohen J.H., Kristal

Clinical Utility of Five Genetic Variants for Predicting Prostate Cancer Risk and Mortality

PubMed Central

Salinas, Claudia A.; Koopmeiners, Joseph S.; Kwon, Erika M.; FitzGerald, Liesel; Lin, Daniel W.; Ostrander, Elaine A.; Feng, Ziding; Stanford, Janet L.

2009-01-01

Background A recent report suggests that the combination of five single-nucleotide polymorphisms (SNPs) at 8q24, 17q12, 17q24.3 and a family history of the disease may predict risk of prostate cancer. The present study tests the performance of these factors in prediction models for prostate cancer risk and prostate cancer-specific mortality. Methods SNPs were genotyped in population-based samples from Caucasians in King County, Washington. Incident cases (n=1308), aged 35–74, were compared to age-matched controls (n=1266) using logistic regression to estimate odds ratios (OR) associated with genotypes and family history. Cox proportional hazards models estimated hazard ratios for prostate cancer-specific mortality according to genotypes. Results The combination of SNP genotypes and family history was significantly associated with prostate cancer risk (ptrend=1.5 × 10−20). Men with ≥ five risk factors had an OR of 4.9 (95% CI 1.6 to 18.5) compared to men with none. However, this combination of factors did not improve the ROC curve after accounting for known risk predictors (i.e., age, serum PSA, family history). Neither the individual nor combined risk factors was associated with prostate cancer-specific mortality. Conclusion Genotypes for five SNPs plus family history are associated with a significant elevation in risk for prostate cancer and may explain up to 45% of prostate cancer in our population. However, they do not improve prediction models for assessing who is at risk of getting or dying from the disease, once known risk or prognostic factors are taken into account. Thus, this SNP panel may have limited clinical utility. PMID:19058137

The Role of c-Myc and miRNAs on EMT and the TGF-betaSwitch in Primary Intermediate Basal Cells Isolated From Prostate Cancer

DTIC Science & Technology

2013-03-01

beta alone and suggested that we attempt to understand the role of ras signaling, as myc is known to be activated downstream of ras( Compere et al...epithelial-mesenchymal transition and invasion in prostate cancer. Carcinogenesis 33, 1965-1975. Compere , S.J., Baldacci, P., Sharpe, A.H., Thompson

Proton Radiotherapy for Prostate Cancer Is Not Associated With Post-Treatment Testosterone Suppression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichols, R. Charles, E-mail: rnichols@floridaproton.org; University of Florida Proton Therapy Institute, Jacksonville, FL; Morris, Christopher G.

Purpose: Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials: Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. Themore » pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results: The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions: Conformal proton therapy to the prostate, as delivered using University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.« less

Gonorrhea infection increases the risk of prostate cancer in Asian population: a nationwide population-based cohort study.

PubMed

Wang, Y-C; Chung, C-H; Chen, J-H; Chiang, M-H; Ti-Yin; Tsao, C-H; Lin, F-H; Chien, W-C; Shang, S-T; Chang, F-Y

2017-05-01

This nationwide population-based retrospective cohort study evaluated the risk of developing prostate cancer among patients with gonorrhea. We identified cases of newly diagnosed gonorrhea in men between 2000 and 2010 from the Taiwan National Health Insurance Research Database. Each patient with gonorrhea was matched to four controls, based on age and index year. All subjects were followed up from the index date to December 31, 2010. The Cox proportional hazards regression model was used to assess the risk of prostate cancer. A total of 355 men were included in the study group, and 1,420 age-matched subjects without gonorrhea were included in the control group. After adjusting for age, comorbidities, urbanization level, hospital level, and monthly income, gonorrhea was significantly associated with an increased risk of prostate cancer (adjusted hazard ratio = 5.66, 95% confidence interval = 1.36-23.52). Men aged 45-70 years and those with lower monthly income were more strongly associated with prostate cancer in the study group than the control group. The higher risk for developing prostate cancer were also found in those without syphilis, without genital warts, without diabetes mellitus, without chronic obstructive pulmonary disease, without benign prostatic hypertrophy, without chronic prostatitis, and without alcoholism. The Kaplan-Meier analysis showed the risk of prostate cancer was significantly higher in the study group than in the control group. Gonorrhea may be involved in the development of prostate cancer. More intensive screening and prevention interventions for prostate cancer should be recommended in men with gonorrhea.

A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population.

PubMed

Marzec, Jacek; Mao, Xueying; Li, Meiling; Wang, Meilin; Feng, Ninghan; Gou, Xin; Wang, Guomin; Sun, Zan; Xu, Jianfeng; Xu, Hua; Zhang, Xiaoping; Zhao, Shan-Chao; Ren, Guoping; Yu, Yongwei; Wu, Yudong; Wu, Ji; Xue, Yao; Zhou, Bo; Zhang, Yanling; Xu, Xingxing; Li, Jie; He, Weiyang; Benlloch, Sara; Ross-Adams, Helen; Chen, Li; Li, Jucong; Hong, Yingqia; Kote-Jarai, Zsofia; Cui, Xingang; Hou, Jianguo; Guo, Jianming; Xu, Lei; Yin, Changjun; Zhou, Yuanping; Neal, David E; Oliver, Tim; Cao, Guangwen; Zhang, Zhengdong; Easton, Douglas F; Chelala, Claude; Al Olama, Ali Amin; Eeles, Rosalind A; Zhang, Hongwei; Lu, Yong-Jie

2016-04-19

Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer.

Comparative Effectiveness of Cancer Control and Survival after Robot-Assisted versus Open Radical Prostatectomy.

PubMed

Hu, Jim C; O'Malley, Padraic; Chughtai, Bilal; Isaacs, Abby; Mao, Jialin; Wright, Jason D; Hershman, Dawn; Sedrakyan, Art

2017-01-01

Robot-assisted surgery has been rapidly adopted in the U.S. for prostate cancer. Its adoption has been driven by market forces and patient preference, and debate continues regarding whether it offers improved outcomes to justify the higher cost relative to open surgery. We examined the comparative effectiveness of robot-assisted vs open radical prostatectomy in cancer control and survival in a nationally representative population. This population based observational cohort study of patients with prostate cancer undergoing robot-assisted radical prostatectomy and open radical prostatectomy during 2003 to 2012 used data captured in the SEER (Surveillance, Epidemiology, and End Results)-Medicare linked database. Propensity score matching and time to event analysis were used to compare all cause mortality, prostate cancer specific mortality and use of additional treatment after surgery. A total of 6,430 robot-assisted radical prostatectomies and 9,161 open radical prostatectomies performed during 2003 to 2012 were identified. The use of robot-assisted radical prostatectomy increased from 13.6% in 2003 to 2004 to 72.6% in 2011 to 2012. After a median followup of 6.5 years (IQR 5.2-7.9) robot-assisted radical prostatectomy was associated with an equivalent risk of all cause mortality (HR 0.85, 0.72-1.01) and similar cancer specific mortality (HR 0.85, 0.50-1.43) vs open radical prostatectomy. Robot-assisted radical prostatectomy was also associated with less use of additional treatment (HR 0.78, 0.70-0.86). Robot-assisted radical prostatectomy has comparable intermediate cancer control as evidenced by less use of additional postoperative cancer therapies and equivalent cancer specific and overall survival. Longer term followup is needed to assess for differences in prostate cancer specific survival, which was similar during intermediate followup. Our findings have significant quality and cost implications, and provide reassurance regarding the adoption of more expensive technology in the absence of randomized controlled trials. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Keratin 13 expression reprograms bone and brain metastases of human prostate cancer cells.

PubMed

Li, Qinlong; Yin, Lijuan; Jones, Lawrence W; Chu, Gina C-Y; Wu, Jason B-Y; Huang, Jen-Ming; Li, Quanlin; You, Sungyong; Kim, Jayoung; Lu, Yi-Tsung; Mrdenovic, Stefan; Wang, Ruoxiang; Freeman, Michael R; Garraway, Isla; Lewis, Michael S; Chung, Leland W K; Zhau, Haiyen E

2016-12-20

Lethal progression of prostate cancer metastasis can be improved by developing animal models that recapitulate the clinical conditions. We report here that cytokeratin 13 (KRT13), an intermediate filament protein, plays a directive role in prostate cancer bone, brain, and soft tissue metastases. KRT13 expression was elevated in bone, brain, and soft tissue metastatic prostate cancer cell lines and in primary and metastatic clinical prostate, lung, and breast cancer specimens. When KRT13 expression was determined at a single cell level in primary tumor tissues of 44 prostate cancer cases, KRT13 level predicted bone metastasis and the overall survival of prostate cancer patients. Genetically enforced KRT13 expression in human prostate cancer cell lines drove metastases toward mouse bone, brain and soft tissues through a RANKL-independent mechanism, as KRT13 altered the expression of genes associated with EMT, stemness, neuroendocrine/neuromimicry, osteomimicry, development, and extracellular matrices, but not receptor activator NF-κB ligand (RANKL) signaling networks in prostate cancer cells. Our results suggest new inhibitors targeting RANKL-independent pathways should be developed for the treatment of prostate cancer bone and soft tissue metastases.

Association Between Cd Exposure and Risk of Prostate Cancer: A PRISMA-Compliant Systematic Review and Meta-Analysis.

PubMed

Ju-Kun, Song; Yuan, Dong-Bo; Rao, Hao-Fu; Chen, Tian-Fei; Luan, Bo-Shi; Xu, Xiao-Ming; Jiang, Fu-Neng; Zhong, Wei-De; Zhu, Jian-Guo

2016-02-01

Several observational studies on the association between Cd exposure and risk of prostate cancer have yielded inconsistent results. To address this issue, we conducted a meta-analysis to evaluate the correlation between Cd exposure and risk of prostate cancer.Relevant studies in PubMed and Embase databases were retrieved until October 2015. We compared the highest and lowest meta-analyses to quantitatively evaluate the relationship between Cd exposure and risk of prostate cancer. Summary estimates were obtained using a random-effects model.In the general population, high Cd exposure was not associated with increased prostate cancer (OR 1.21; 95% CI 0.91-1.64), whereas the combined standardized mortality ratio of the association between Cd exposure and risk of prostate cancer was 1.66 (95% CI 1.10-2.50) in populations exposed to occupational Cd. In addition, high D-Cd intake (OR 1.07; 95% CI 0.96-1.20) and U-Cd concentration (OR 0.86; 95% CI 0.48-1.55) among the general population was not related to the increased risk of prostate cancer. In the dose analysis, the summary relative risk was 1.07 (95% CI 0.73-1.57) for each 0.5 μg/g creatinine increase in U-Cd and 1.02 (95% CI 0.99-1.06) for each 10 μg/day increase of dietary Cd intake. However, compared with nonoccupational exposure, high occupational Cd exposure may be associated with the increased risk of prostate cancer.This meta-analysis suggests high Cd exposure as a risk factor for prostate cancer in occupational rather than nonoccupational populations. However, these results should be carefully interpreted because of the significant heterogeneity among studies. Additional large-scale and high-quality prospective studies are needed to confirm the association between Cd exposure and risk of prostate cancer.

Association Between Cd Exposure and Risk of Prostate Cancer

PubMed Central

Ju-Kun, Song; Yuan, Dong-Bo; Rao, Hao-Fu; Chen, Tian-Fei; Luan, Bo-Shi; Xu, Xiao-Ming; Jiang, Fu-Neng; Zhong, Wei-De; Zhu, Jian-Guo

2016-01-01

Abstract Several observational studies on the association between Cd exposure and risk of prostate cancer have yielded inconsistent results. To address this issue, we conducted a meta-analysis to evaluate the correlation between Cd exposure and risk of prostate cancer. Relevant studies in PubMed and Embase databases were retrieved until October 2015. We compared the highest and lowest meta-analyses to quantitatively evaluate the relationship between Cd exposure and risk of prostate cancer. Summary estimates were obtained using a random-effects model. In the general population, high Cd exposure was not associated with increased prostate cancer (OR 1.21; 95% CI 0.91–1.64), whereas the combined standardized mortality ratio of the association between Cd exposure and risk of prostate cancer was 1.66 (95% CI 1.10–2.50) in populations exposed to occupational Cd. In addition, high D-Cd intake (OR 1.07; 95% CI 0.96–1.20) and U-Cd concentration (OR 0.86; 95% CI 0.48–1.55) among the general population was not related to the increased risk of prostate cancer. In the dose analysis, the summary relative risk was 1.07 (95% CI 0.73–1.57) for each 0.5 μg/g creatinine increase in U-Cd and 1.02 (95% CI 0.99–1.06) for each 10 μg/day increase of dietary Cd intake. However, compared with nonoccupational exposure, high occupational Cd exposure may be associated with the increased risk of prostate cancer. This meta-analysis suggests high Cd exposure as a risk factor for prostate cancer in occupational rather than nonoccupational populations. However, these results should be carefully interpreted because of the significant heterogeneity among studies. Additional large-scale and high-quality prospective studies are needed to confirm the association between Cd exposure and risk of prostate cancer. PMID:26871808

Epidemiology of prostatitis

PubMed Central

Krieger, John N.; Lee, Shaun Wen Huey; Jeon, Jeonseong; Cheah, Phaik Yeong; Liong, Men Long; Riley, Donald E.

2008-01-01

Background Prostatitis describes a combination of infectious diseases (acute and chronic bacterial prostatitis), chronic pelvic pain syndrome, and asymptomatic inflammation. Materials and methods We employed evidence-based methods to review the epidemiology of prostatitis syndromes. Results The prevalence of prostatitis symptoms could be compared in five studies surveying 10 617 men. Overall, 873 participants met various criteria for prostatitis, representing an overall rate of 8.2%, with prevalence ranging from 2.2 to 9.7%. A history of sexually transmitted diseases was associated with an increased risk for prostatitis symptoms. Men reporting a history of prostatitis symptoms had a substantially increased rate of benign prostatic hyperplasia, lower urinary tract symptoms and prostate cancer. In one study, the incidence of physician-diagnosed prostatitis was 4.9 cases per 1000 person-years. Two studies suggest that about one-third of men reporting prostatitis symptoms had resolution after 1 year. Patients with previous episodes and more severe symptoms are at higher risk for chronic pelvic pain. Discussion The prevalence of prostatitis symptoms is high, comparable to rates of ischamic heart disease and diabetes. Clinical evaluation appears necessary to verify that prostatitis is responsible for patients’ symptoms. Prostatitis symptoms may increase a man’s risk for benign prostate hypertrophy, lower urinary tract symptoms and prostate cancer. We need to define natural history and consequences of prostatitis, develop better algorithms for diagnosis and treatment, and develop strategies for prevention. PMID:18164907

A prospective analysis of the association between dietary fiber intake and prostate cancer risk in EPIC.

PubMed

Suzuki, Reiko; Allen, Naomi E; Key, Timothy J; Appleby, Paul N; Tjønneland, Anne; Johnsen, Nina Føns; Jensen, Majken K; Overvad, Kim; Boeing, Heiner; Pischon, Tobias; Kaaks, Rudolf; Rohrmann, Sabine; Trichopoulou, Antonia; Misirli, Gesthimani; Trichopoulos, Dimitrios; Bueno-de-Mesquita, H Bas; van Duijnhoven, Fränzel; Sacerdote, Carlotta; Pala, Valeria; Palli, Domenico; Tumino, Rosario; Ardanaz, Eva; Quirós, José Ramón; Larrañaga, Nerea; Sánchez, Maria-José; Tormo, María-José; Jakszyn, Paula; Johansson, Ingegerd; Stattin, Pär; Berglund, Göran; Manjer, Jonas; Bingham, Sheila; Khaw, Kay-Tee; Egevad, Lars; Ferrari, Pietro; Jenab, Mazda; Riboli, Elio

2009-01-01

Few studies have examined the association between dietary fiber intake and prostate cancer risk. We evaluated the association between dietary fiber intake and the risk of prostate cancer among 142,590 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Consumption of dietary fiber (total, cereal, fruit and vegetable fiber) was estimated by validated dietary questionnaires and calibrated using 24-hr dietary recalls. Incidence rate ratios were estimated using Cox regression and adjusted for potential confounding factors. During an average of 8.7 years follow-up, prostate cancer was diagnosed in 2,747 men. Overall, there was no association between dietary fiber intake (total, cereal, fruit or vegetable fiber) and prostate cancer risk, although calibrated intakes of total fiber and fruit fiber were associated with nonstatistically significant reductions in risk. There was no association between fiber derived from cereals or vegetables and risk and no evidence for heterogeneity in any of the risk estimates by stage or grade of disease. Our results suggest that dietary fiber intake is not associated with prostate cancer risk.

Significance of common variants on human chromosome 8q24 in relation to the risk of prostate cancer in native Japanese men

PubMed Central

Liu, Miao; Kurosaki, Takayuki; Suzuki, Motofumi; Enomoto, Yutaka; Nishimatsu, Hiroaki; Arai, Tomio; Sawabe, Motoji; Hosoi, Takayuki; Homma, Yukio; Kitamura, Tadaichi

2009-01-01

Background Common variants on human chromosome 8q24, rs1447295 (C/A) and rs6983267 (T/G), have been recently linked to the prevalence of prostate cancer in European and American populations. Here, we evaluated whether the single-nucleotide polymorphisms rs1447295 and rs6983267 were associated with the risk of sporadic prostate cancer as well as latent prostate cancer in a native Japanese population. Results We analyzed genomic DNA samples from 391 sporadic prostate cancer patients, 323 controls who had died from causes unrelated to cancer and 112 Japanese men who were diagnosed as having latent prostate cancer based on autopsy results. The polymorphisms were determined by allelic discrimination using a fluorescent-based TaqMan assay. The A allele of rs1447295 was significantly associated with the risk of sporadic prostate cancer (p = 0.04; age-adjusted OR, 1.34), while the G allele of rs6983267 showed a trend towards being a high-risk allele (p = 0.06; age-adjusted OR, 1.27). No significant difference between these two polymorphisms and the risk of latent prostate cancer was observed in the present Japanese population. Conclusion Known variants on human chromosome 8q24 may be risk factors for sporadic prostate cancer in native Japanese men. PMID:19602258

The emerging role of obesity, diet and lipid metabolism in prostate cancer.

PubMed

Ferro, Matteo; Terracciano, Daniela; Buonerba, Carlo; Lucarelli, Giuseppe; Bottero, Danilo; Perdonà, Sisto; Autorino, Riccardo; Serino, Alessandro; Cantiello, Francesco; Damiano, Rocco; Andras, Iulia; De Placido, Sabino; Di Lorenzo, Giuseppe; Battaglia, Michele; Jereczek-Fossa, Barbara A; Mirone, Vincenzo; De Cobelli, Ottavio

2017-02-01

Obesity is associated with an increased risk of a number of serious medical conditions, including cancer. As far as prostate cancer is concerned, obesity is associated with an increased risk of high-grade tumors, which is possibly related to lower androgen levels. Diet may also affect prostate cancer risk since countries with a higher dietary fat intake also present higher prostate cancer mortality rates. Interestingly, prostate cancer is associated with a number of metabolic alterations that may provide valuable diagnostic and therapeutic targets. This review explores the available clinical as well as biological evidence supporting the relationship between obesity, diet, alteration in metabolic pathways and prostate cancer.

Renal donors with prostate cancer, no longer a reason to decline.

PubMed

Dholakia, S; Johns, R; Muirhead, L; Papalois, V; Crane, J

2016-01-01

To fully assess the true risk of prostate cancer transmission in during renal transplantation. A full review of all existing literature relevant to the topic. There has not been a single documented case of transmission of prostate cancer during renal transplant. Prostate cancer in deceased organ donors has an incidence estimated between 3% and 18.5% and over 100 transplants have been performed using organs from donor with proven prostate cancer without issue. Transmission of prostate cancer through kidney transplantation seems very unlikely. The risks of remaining on the waiting list are outweighed by a transmission risk and the potential benefit makes the case to have clear guidelines about donor prostate malignancy when accepting potential organs. Copyright © 2015. Published by Elsevier Inc.

Egg, red meat, and poultry intake and risk of lethal prostate cancer in the prostate specific antigen-era: incidence and survival

PubMed Central

Richman, Erin L.; Kenfield, Stacey A.; Stampfer, Meir J.; Giovannucci, Edward L.; Chan, June M.

2011-01-01

Red and processed meat may increase risk of advanced prostate cancer. Data on post-diagnostic diet and prostate cancer are sparse, but post-diagnostic intake of poultry with skin and eggs may increase risk of disease progression. Therefore, we prospectively examined total, unprocessed, and processed red meat, poultry, and eggs in relation to risk of lethal prostate cancer (e.g. men without cancer at baseline who developed distant organ metastases or died from prostate cancer during follow-up) among 27, 607 men followed from 1994–2008. We also performed a case-only survival analysis to examine post-diagnostic consumption of these foods and risk of lethal prostate cancer among the 3,127 men initially diagnosed with non-metastatic prostate cancer during follow-up. In the incidence analysis, we observed 199 events during 306,715 person-years. Men who consumed 2.5 or more eggs per week had an 81% increased risk of lethal prostate cancer compared to men who consumed less than 0.5 eggs per week (HR: 1.81; 95% confidence interval (CI): 1.13, 2.89; p-trend: 0.01). In the case-only survival analysis, we observed 123 events during 19,354 person-years. There were suggestive, but not statistically significant, positive associations between post-diagnostic poultry (HR ≥3.5 vs. <1.5 servings per week: 1.69; 95%CI: 0.96, 2.99; p-trend: 0.07) and post-diagnostic processed red meat (HR ≥3 vs. <0.5 servings per week: 1.45; 95%CI: 0.73, 2.87; p-trend: 0.08) and risk of progression of localized prostate cancer to lethal disease. In conclusion, consumption of eggs may increase risk of developing a lethal-form of prostate cancer among healthy men. PMID:21930800

Case-control study of prostatic cancer in employees of the United Kingdom Atomic Energy Authority.

PubMed Central

Rooney, C; Beral, V; Maconochie, N; Fraser, P; Davies, G

1993-01-01

OBJECTIVE--To investigate the relation between risk of prostatic cancer and occupational exposures, especially to radionuclides, in employees of the United Kingdom Atomic Energy Authority. DESIGN--Case-control study of men with prostatic cancer and matched controls. Information about sociodemographic factors and exposures to radionuclides and other substances was abstracted and classified for each subject from United Kingdom Atomic Energy Authority records without knowledge of who had cancer. SUBJECTS--136 men with prostatic cancer diagnosed between 1946 and 1986 and 404 matched controls, all employees of United Kingdom Atomic Energy Authority. MAIN OUTCOME MEASURES--Documented or possible contamination with specific radionuclides. RESULTS--Risk of prostatic cancer was significantly increased in men who were internally contaminated with or who worked in environments potentially contaminated by tritium, chromium-51, iron-59, cobalt-60, or zinc-65. Internal contamination with at least one of the five radionuclides was detected in 14 men with prostatic cancer (10%) and 12 controls (3%) (relative risk 5.32 (95% confidence interval 1.87 to 17.24). Altogether 28 men with prostatic cancer (21%) and 46 controls (11%) worked in environments potentially contaminated by at least one of the five radionuclides (relative risk 2.36 (1.26 to 4.43)); about two thirds worked at heavy water reactors (19 men with prostatic cancer and 32 controls (relative risk 2.13 (1.00 to 4.52)). Relative risk of prostatic cancer increased with increasing duration of work in places potentially contaminated by these radionuclides and with increasing level of probable contamination. Prostatic cancer was not associated with exposure to plutonium, uranium, cadmium, boron, beryllium, or organic or inorganic chemicals. CONCLUSIONS--Risk of prostatic cancer risk was increased in United Kingdom Atomic Energy Authority workers who were occupationally exposed to tritium, 51Cr, 59Fe, 60Co, or 65Zn. Exposure to these radionuclides was infrequent, and their separate effects could not be evaluated. PMID:8274891

Association between drinking water uranium content and cancer risk in Bavaria, Germany.

PubMed

Radespiel-Tröger, M; Meyer, M

2013-10-01

To evaluate the possible association between uranium (U) content in public drinking water on the one hand and the risk of cancer of the colorectum, lung, female breast, prostate, kidney, and urinary bladder, total cancer, and leukemia on the other hand in Bavaria, an ecologic study on the level of municipalities was performed. Cancer incidence data for the years 2002-2008 were obtained from the population-based cancer registry Bavaria according to sex. Current U content data of public drinking water on the level of municipalities were obtained from a publicly available source. The possible association between drinking water U content and cancer risk adjusted for average socio-economic status was evaluated using Poisson regression. Drinking water U content was below 20 μg/L in 458 out of 461 included municipalities. We found a significantly increased risk of leukemia in men in the intermediate (U level, 1.00-4.99 μg/L; relative risk [RR], 1.14) and in the highest U exposure category (U level, ≥5 μg/L; RR, 1.28). Moreover, in women, a significantly elevated risk was identified with respect to kidney cancer in the highest exposure category (RR, 1.16) and with respect to lung cancer in the intermediate exposure category (RR, 1.12). The slightly increased risk of leukemia in men, kidney cancer in women, and lung cancer in women may require further investigation. If an increased cancer risk is confirmed, preventive measures (e.g., introduction of U filters in public water systems) may be considered.

Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer

PubMed Central

Wilcox, Shea W; Aherne, Noel J; Benjamin, Linus C; Wu, Bosco; de Campos Silva, Thomaz; McLachlan, Craig S; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

2014-01-01

Purpose Dose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT. Methods and materials Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Results Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis. Conclusion There is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses and compares favorably with published series for the treatment of prostate cancer. PMID:25210465

Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer.

PubMed

Wilcox, Shea W; Aherne, Noel J; Benjamin, Linus C; Wu, Bosco; de Campos Silva, Thomaz; McLachlan, Craig S; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

2014-01-01

Dose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT. Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis. There is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses and compares favorably with published series for the treatment of prostate cancer.

Temporarily deferred therapy (watchful waiting) for men younger than 70 years and with low-risk localized prostate cancer in the prostate-specific antigen era.

PubMed

Carter, Corey A; Donahue, Timothy; Sun, Leon; Wu, Hongyu; McLeod, David G; Amling, Christopher; Lance, Raymond; Foley, John; Sexton, Wade; Kusuda, Leo; Chung, Andrew; Soderdahl, Douglas; Jackmaan, Stephen; Moul, Judd W

2003-11-01

Watchful waiting (WW) is an acceptable strategy for managing prostate cancer (PC) in older men. Prostate-specific antigen (PSA) testing has resulted in a stage migration, with diagnoses made in younger men. An analysis of the Department of Defense Center for Prostate Disease Research Database was undertaken to document younger men with low- or intermediate-grade PC who initially chose WW. We identified men choosing WW who were diagnosed between January 1991 and January 2002, were 70 years or younger, had a Gleason score < or = 6 with no Gleason pattern 4, had no more than three positive cores on biopsy, and whose clinical stage was < or = T2 and PSA level was < or = 20. We analyzed their likelihood of remaining on WW, the factors associated with secondary treatment, and the influence of comorbidities. Three hundred thirteen men were identified. Median follow-up time was 3.8 years. Median age was 65.4 years (range, 41 to 70 years). Ninety-eight patients remained on WW; 215 proceeded to treatment. A total of 57.3% and 73.2% chose treatment within the first 2 and 4 years, respectively. Median PSA doubling time (DT) was 2.5 years for those who underwent therapy; those remaining on WW had a median DT of 25.8 years. The type of secondary treatment was associated with the number of patient's comorbidities (P =.012). Younger patients who choose WW seemed more likely to receive secondary treatment than older patients. PSA DTs often predict the use of secondary treatment. The number of comorbidities a patient has influences the type of secondary therapy chosen. The WW strategy may better be termed temporarily deferred therapy.

Psychological impact of serial prostate-specific antigen tests in Japanese men waiting for prostate biopsy.

PubMed

Kobayashi, Minoru; Nukui, Akinori; Kamai, Takao

2017-02-01

It is common to repeat prostate-specific antigen (PSA) measurements for men with intermediate PSA elevation before prostate biopsy. In this scenario, men with persistently elevated PSA values may have considerable psychological distress. We attempted to determine whether elevated PSA values have psychological effects on these men in association with the timing of measurement, PSA kinetics, and biopsy results. In order to investigate the initial and late effects of PSA tests on psychological distress during serial measurements, two groups of men with screen-positive results (PSA ≥3 ng/ml) were studied-205 men whose first questionnaires regarding anxiety and depression were taken at initial screening (group A), and 103 men whose questionnaires were taken at repeated measurement for prior PSA elevation (group B). The level of distress was generally low. There were no significant differences in distress between the two groups, suggesting a constant psychological effect by elevated PSA values over a long period of time. The distress of men in group A increased significantly as PSA levels rose and decreased when they fell to normal range. On the other hand, the distress of men in group B did not change regardless of PSA kinetics, indicating that their psychological condition seemed susceptible to subtle PSA change only in the initial phase of measurements. Unexpectedly, men with benign results showed insignificant but higher distress after prostate biopsy. Although a small fraction of men have psychological distress caused by changes in PSA levels, the benefits, risks (psychological and physical), and limitations of PSA tests must be adequately explained to the patients before entering the screening program.

Treatment plan comparison between Tri-Co-60 magnetic-resonance image-guided radiation therapy and volumetric modulated arc therapy for prostate cancer

PubMed Central

Park, Jong Min; Park, So-Yeon; Choi, Chang Heon; Chun, Minsoo; Kim, Jin Ho; Kim, Jung-In

2017-01-01

To investigate the plan quality of tri-Co-60 intensity-modulated radiation therapy (IMRT) with magnetic-resonance image-guided radiation therapy compared with volumetric-modulated arc therapy (VMAT) for prostate cancer. Twenty patients with intermediate-risk prostate cancer, who received radical VMAT were selected. Additional tri-Co-60 IMRT plans were generated for each patient. Both primary and boost plans were generated with tri-Co-60 IMRT and VMAT techniques. The prescription doses of the primary and boost plans were 50.4 Gy and 30.6 Gy, respectively. The primary and boost planning target volumes (PTVs) of the tri-Co-60 IMRT were generated with 3 mm margins from the primary clinical target volume (CTV, prostate + seminal vesicle) and a boost CTV (prostate), respectively. VMAT had a primary planning target volume (primary CTV + 1 cm or 2 cm margins) and a boost PTV (boost CTV + 0.7 cm margins), respectively. For both tri-Co-60 IMRT and VMAT, all the primary and boost plans were generated that 95% of the target volumes would be covered by the 100% of the prescription doses. Sum plans were generated by summation of primary and boost plans. In sum plans, the average values of V70 Gy of the bladder of tri-Co-60 IMRT vs. VMAT were 4.0% ± 3.1% vs. 10.9% ± 6.7%, (p < 0.001). Average values of V70 Gy of the rectum of tri-Co-60 IMRT vs. VMAT were 5.2% ± 1.8% vs. 19.1% ± 4.0% (p < 0.001). The doses of tri-Co-60 IMRT delivered to the bladder and rectum were smaller than those of VMAT while maintaining identical target coverage in both plans. PMID:29207634

Moderate hypofractionated radiotherapy with volumetric modulated arc therapy and simultaneous integrated boost for pelvic irradiation in prostate cancer.

PubMed

Franzese, C; Fogliata, A; D'Agostino, G R; Di Brina, L; Comito, T; Navarria, P; Cozzi, L; Scorsetti, M

2017-07-01

The optimal treatment for unfavourable intermediate/high-risk prostate cancer is still debated. In the present study, the pattern of toxicity and early clinical outcome of patients with localized prostate cancer was analyzed. A cohort of 90 patients treated on pelvic lymph nodes from 2010 to 2015 was selected. All patients were treated with Volumetric Modulated Arc Therapy (VMAT), and Simultaneous integrated boost (SIB) in 28 fractions; the prostate, the seminal vesicle and the pelvic lymph node received total doses of 74.2, 65.5, and 51.8 Gy, respectively. End points were the detection of acute and late toxicities graded according to the Common Toxicity Criteria CTCAE version 3, evaluating the rectal, genito-urinary and gastro-intestinal toxicity. Correlation of OARs dose parameters and related toxicities was explored. Preliminary overall survival and Progression-free survival (PFS) were evaluated. With a median follow-up of 25 months, no interruptions for treatment-related toxicity were recorded. Univariate analysis among dosimetric data and acute toxicities showed no correlations. Regarding late toxicity: the dose received by a rectal volume of 90 cm 3 was found to be significant for toxicity prediction (p = 0.024). PFS was 90.6% and 60.2% at 2 and 4 years, respectively. PFS correlates with age (p = 0.011) and Gleason score (p = 0.011). Stratifying the PSA nadir in quartiles, its value was significant (p = 0.016) in predicting PFS, showing a reduction of PFS of 2 months for each PSA-nadir increase of 0.1 ng/ml. HRT with VMAT and SIB on the whole pelvis in unfavourable prostate cancer patients is effective with a mild pattern of toxicity.

Dose-Fractionation Sensitivity of Prostate Cancer Deduced From Radiotherapy Outcomes of 5,969 Patients in Seven International Institutional Datasets: {alpha}/{beta} = 1.4 (0.9-2.2) Gy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miralbell, Raymond, E-mail: Raymond.Miralbell@hcuge.ch; Institut Oncologic Teknon, Barcelona; Roberts, Stephen A.

2012-01-01

Purpose: There are reports of a high sensitivity of prostate cancer to radiotherapy dose fractionation, and this has prompted several trials of hypofractionation schedules. It remains unclear whether hypofractionation will provide a significant therapeutic benefit in the treatment of prostate cancer, and whether there are different fractionation sensitivities for different stages of disease. In order to address this, multiple primary datasets have been collected for analysis. Methods and Materials: Seven datasets were assembled from institutions worldwide. A total of 5969 patients were treated using external beams with or without androgen deprivation (AD). Standard fractionation (1.8-2.0 Gy per fraction) was usedmore » for 40% of the patients, and hypofractionation (2.5-6.7 Gy per fraction) for the remainder. The overall treatment time ranged from 1 to 8 weeks. Low-risk patients comprised 23% of the total, intermediate-risk 44%, and high-risk 33%. Direct analysis of the primary data for tumor control at 5 years was undertaken, using the Phoenix criterion of biochemical relapse-free survival, in order to calculate values in the linear-quadratic equation of k (natural log of the effective target cell number), {alpha} (dose-response slope using very low doses per fraction), and the ratio {alpha}/{beta} that characterizes dose-fractionation sensitivity. Results: There was no significant difference between the {alpha}/{beta} value for the three risk groups, and the value of {alpha}/{beta} for the pooled data was 1.4 (95% CI = 0.9-2.2) Gy. Androgen deprivation improved the bNED outcome index by about 5% for all risk groups, but did not affect the {alpha}/{beta} value. Conclusions: The overall {alpha}/{beta} value was consistently low, unaffected by AD deprivation, and lower than the appropriate values for late normal-tissue morbidity. Hence the fractionation sensitivity differential (tumor/normal tissue) favors the use of hypofractionated radiotherapy schedules for all risk groups, which is also very beneficial logistically in limited-resource settings.« less

Sequence variants of Toll-like receptor 4 and susceptibility to prostate cancer.

PubMed

Chen, Yen-Ching; Giovannucci, Edward; Lazarus, Ross; Kraft, Peter; Ketkar, Shamika; Hunter, David J

2005-12-15

Chronic inflammation has been hypothesized to be a risk factor for prostate cancer. The Toll-like receptor 4 (TLR4) presents the bacterial lipopolysaccharide (LPS), which interacts with ligand-binding protein and CD14 (LPS receptor) and activates expression of inflammatory genes through nuclear factor-kappaB and mitogen-activated protein kinase signaling. A previous case-control study found a modest association of a polymorphism in the TLR4 gene [11381G/C, GG versus GC/CC: odds ratio (OR), 1.26] with risk of prostate cancer. We assessed if sequence variants of TLR4 were associated with the risk of prostate cancer. In a nested case-control design within the Health Professionals Follow-up Study, we identified 700 participants with prostate cancer diagnosed after they had provided a blood specimen in 1993 and before January 2000. Controls were 700 age-matched men without prostate cancer who had had a prostate-specific antigen test after providing a blood specimen. We genotyped 16 common (>5%) single nucleotide polymorphisms (SNP) discovered in a resequencing study spanning TLR4 to test for association between sequence variation in TLR4 and prostate cancer. Homozygosity for the variant alleles of eight SNPs was associated with a statistically significantly lower risk of prostate cancer (TLR4_1893, TLR4_2032, TLR4_2437, TLR4_7764, TLR4_11912, TLR4_16649, TLR4_17050, and TLR4_17923), but the TLR4_15844 polymorphism corresponding to 11381G/C was not associated with prostate cancer (GG versus CG/CC: OR, 1.01; 95% confidence interval, 0.79-1.29). Six common haplotypes (cumulative frequency, 81%) were observed; the global test for association between haplotypes and prostate cancer was statistically significant (chi(2) = 14.8 on 6 degrees of freedom; P = 0.02). Two common haplotypes were statistically significantly associated with altered risk of prostate cancer. Inherited polymorphisms of the innate immune gene TLR4 are associated with risk of prostate cancer.

Bisphenol A and other environmental risk factors for prostate cancer in Hong Kong.

PubMed

Tse, Lap Ah; Lee, Priscilla Ming Yi; Ho, Wing Ming; Lam, Augustine Tsan; Lee, Man Kei; Ng, Simon Siu Man; He, Yonghua; Leung, Ka-Sing; Hartle, Jennifer C; Hu, Howard; Kan, Haidong; Wang, Feng; Ng, Chi Fai

2017-10-01

Environmental exposures are contributing factors to prostate cancer etiology, but these remain unclear. We aimed to document the associations between environmental risk factors and prostate cancer in Chinese, with special reference to bisphenol A (BPA). We recruited 431 newly diagnosed prostate cancer cases and 402 age-matched controls from Prince of Wales Hospital in Hong Kong. We obtained each participant's clinical data and epidemiological information on chronic BPA exposure and other environmental risk factors (e.g., dietary habits, occupation and shift work) using a standard questionnaire. A new assessment tool of environmental BPA exposure was developed and replicated. Multiple logistic regression analysis was performed to examine odds ratio (OR) and 95% confidence interval (95% CI) for the association of prostate cancer with a novel cumulative BPA exposure index (CBPAI) and other environmental risk factors. Weekly consumption of deep fried food (OR=1.85, 95% CI: 1.15-2.95) and pickled vegetable (OR=1.87, 95% CI: 1.07-3.28) was significantly associated with excessive prostate cancer risk. Prostate cancer was positively associated with nightshift work (OR=1.76, 95% CI: 1.07-2.89) and it was negatively associated with green tea drinking (OR=0.56, 95% CI: 0.34-0.91). There was a positive exposure-response relationship between CBPAI and prostate cancer, with the greatest and significant risk in the high versus reference category (OR=1.57, 95% CI: 1.01-2.44). Frequent consumption of deep fried food and pickled vegetable, non-habitual green tea drinking and nightshift work are the contributing risk factors to prostate cancer in Hong Kong Chinese. More importantly, this study provides the first epidemiological evidence on carcinogenicity of BPA on the human prostate. Copyright © 2017. Published by Elsevier Ltd.

Vitamins, Metabolomics and Prostate Cancer

PubMed Central

Mondul, Alison M; Weinstein, Stephanie J; Albanes, Demetrius

2016-01-01

Purpose How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms by which vitamins influence prostate cancer risk. Methods Prostate cancer risk data related to vitamins E, A, and D and metabolomics profiling from clinical, cohort, and nested case-control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes. Results Higher vitamin E serologic status is associated with lower prostate cancer risk, and vitamin E genetic variant data support this. By contrast, controlled vitamin E supplementation trials have mixed results based on differing designs and dosages. Beta-carotene supplementation (in smokers) and higher circulating retinol and 25-hydroxy-vitamin D concentrations appear related to elevated prostate cancer risk. Our prospective metabolomics profiling of fasting serum collected 1-20 years prior to clinical diagnoses found lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with risk of aggressive disease. Conclusions Several active leads exist regarding the role of micronutrients and metabolites in prostate cancer carcinogenesis and risk. How vitamins D and A may adversely impact risk, and whether low-dose vitamin E supplementation remains a viable preventive approach, require further study. PMID:27339624

Vitamins, metabolomics, and prostate cancer.

PubMed

Mondul, Alison M; Weinstein, Stephanie J; Albanes, Demetrius

2017-06-01

How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms through which vitamins influence prostate cancer risk. Prostate cancer risk data related to vitamins E, A, and D and metabolomic profiling from clinical, cohort, and nested case-control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes. Higher vitamin E serologic status is associated with lower prostate cancer risk, and vitamin E genetic variant data support this. By contrast, controlled vitamin E supplementation trials have had mixed results based on differing designs and dosages. Beta-carotene supplementation (in smokers) and higher circulating retinol and 25-hydroxy-vitamin D concentrations appear related to elevated prostate cancer risk. Our prospective metabolomic profiling of fasting serum collected 1-20 years prior to clinical diagnoses found reduced lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with lower risk of aggressive disease. Several active leads exist regarding the role of micronutrients and metabolites in prostate cancer carcinogenesis and risk. How vitamins D and A may adversely impact risk, and whether low-dose vitamin E supplementation remains a viable preventive approach, require further study.

Meat and dairy consumption and subsequent risk of prostate cancer in a US cohort study.

PubMed

Rohrmann, Sabine; Platz, Elizabeth A; Kavanaugh, Claudine J; Thuita, Lucy; Hoffman, Sandra C; Helzlsouer, Kathy J

2007-02-01

To evaluate the association of meat and dairy food consumption with subsequent risk of prostate cancer. In 1989, 3,892 men 35+ years old, who participated in CLUE II study of Washington County, MD, completed an abbreviated Block food frequency questionnaire. Intake of meat and dairy related foods was calculated using consumption frequency and portion size. Incident prostate cancer cases (n = 199) were ascertained through October 2004. Cox proportional hazards regression was used to calculate hazard ratios (HR) of total and advanced (SEER states three and four; n = 54) prostate cancer and 95% confidence intervals (CI) adjusted for age, BMI at age 21, and intake of energy, saturated fat, and tomato products. Intakes of total mean (HR = 0.90, 95% CI 0.60-1.33, comparing highest to lowest tertile) and red meat (HR = 0.87, 95% CI 0.59-1.32) were not statistically significantly associated with prostate cancer. However, processed meat consumption was associated with a non-statistically significant higher risk of total (5+ vs. < or =1 servings/week: HR = 2.24; 95% CI 0.90-5.59) prostate cancer. There was no association across tertiles of dairy or calcium with total prostate cancer, although compared tp < or =1 servings/week consumption of 5+ servings/week of dairy foods was associated with an increased risk of prostate cancer (HR = 1.65, 98% CI 1.02-2.66). Overall, consumption of processed meat, but not total meat or red meat, was associated with a possible increased risk of total prostate cancer in this prospective study. Higher intake of dairy foods but not calcium was positively associated with prostate cancer. Further investigation into the mechanisms by which processed meat and dairy consumption might increase the risk of prostate cancer is suggested.

A Pooled Analysis of 15 Prospective Cohort Studies on the Association between Fruit, Vegetable, and Mature Bean Consumption and Risk of Prostate Cancer.

PubMed

Petimar, Joshua; Wilson, Kathryn M; Wu, Kana; Wang, Molin; Albanes, Demetrius; van den Brandt, Piet A; Cook, Michael B; Giles, Graham G; Giovannucci, Edward L; Goodman, Gary E; Goodman, Phyllis J; Håkansson, Niclas; Helzlsouer, Kathy; Key, Timothy J; Kolonel, Laurence N; Liao, Linda M; Männistö, Satu; McCullough, Marjorie L; Milne, Roger L; Neuhouser, Marian L; Park, Yikyung; Platz, Elizabeth A; Riboli, Elio; Sawada, Norie; Schenk, Jeannette M; Tsugane, Shoichiro; Verhage, Bas; Wang, Ying; Wilkens, Lynne R; Wolk, Alicja; Ziegler, Regina G; Smith-Warner, Stephanie A

2017-08-01

Background: Relationships between fruit, vegetable, and mature bean consumption and prostate cancer risk are unclear. Methods: We examined associations between fruit and vegetable groups, specific fruits and vegetables, and mature bean consumption and prostate cancer risk overall, by stage and grade, and for prostate cancer mortality in a pooled analysis of 15 prospective cohorts, including 52,680 total cases and 3,205 prostate cancer-related deaths among 842,149 men. Diet was measured by a food frequency questionnaire or similar instrument at baseline. We calculated study-specific relative risks using Cox proportional hazards regression, and then pooled these estimates using a random effects model. Results: We did not observe any statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group (including total fruits and vegetables, total fruits, total vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato products), nor specific fruit and vegetables. In addition, we observed few statistically significant results for other prostate cancer outcomes. Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09. There was no evidence of effect modification for any association by age or body mass index. Conclusions: Results from this large, international, pooled analysis do not support a strong role of collective groupings of fruits, vegetables, or mature beans in prostate cancer. Impact: Further investigation of other dietary exposures, especially indicators of bioavailable nutrient intake or specific phytochemicals, should be considered for prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(8); 1276-87. ©2017 AACR . ©2017 American Association for Cancer Research.

Predictive value of different prostate-specific antigen-based markers in men with baseline total prostate-specific antigen <2.0 ng/mL.

PubMed

Fujizuka, Yuji; Ito, Kazuto; Oki, Ryo; Suzuki, Rie; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Suzuki, Kazuhiro

2017-08-01

To investigate the predictive value of various molecular forms of prostate-specific antigen in men with baseline prostate-specific antigen <2.0 ng/mL. The case cohort comprised 150 men with a baseline prostate-specific antigen level <2.0 ng/mL, and who developed prostate cancer within 10 years. The control cohort was 300 baseline prostate-specific antigen- and age-adjusted men who did not develop prostate cancer. Serum prostate-specific antigen, free prostate-specific antigen, and [-2] proenzyme prostate-specific antigen were measured at baseline and last screening visit. The predictive impact of baseline prostate-specific antigen- and [-2] proenzyme prostate-specific antigen-related indices on developing prostate cancer was investigated. The predictive impact of those indices at last screening visit and velocities from baseline to final screening on tumor aggressiveness were also investigated. The baseline free to total prostate-specific antigen ratio was a significant predictor of prostate cancer development. The odds ratio was 6.08 in the lowest quintile baseline free to total prostate-specific antigen ratio subgroup. No serum indices at diagnosis were associated with tumor aggressiveness. The Prostate Health Index velocity and [-2] proenzyme prostate-specific antigen/free prostate-specific antigen velocity significantly increased in patients with higher risk D'Amico risk groups and higher Gleason scores. Free to total prostate-specific antigen ratio in men with low baseline prostate-specific antigen levels seems to predict the risk of developing prostate cancer, and it could be useful for a more effective individualized screening system. Longitudinal changes in [-2] proenzyme prostate-specific antigen-related indices seem to correlate with tumor aggressiveness, and they could be used as prognostic tool before treatment and during active surveillance. © 2017 The Japanese Urological Association.

Understanding Prostate Changes

Cancer.gov

Prostate changes and symptoms that are not cancer. Learn about symptoms, risk factors, and treatment for prostatitis, enlarged prostate (BPH), prostate cancer. Talk with doctor about prostate cancer screening tests (DRE, PSA), biopsy, and Gleason score.

Glandular differentiation in dedifferentiated chondrosarcoma: molecular evidence of a rare phenomenon.

PubMed

Jour, George; Liu, Yajuan; Ricciotti, Robert; Pritchard, Colin; Hoch, Benjamin L

2015-09-01

Epithelial glandular differentiation in dedifferentiated chondrosarcoma has not been described. Our patient was a 64-year-old man with a history of prostate cancer status post-radiation and hormonal therapy. On screening bone scan, he was found to have increased uptake in his right femoral shaft. Biopsy revealed intermediate-grade conventional chondrosarcoma. Subsequent femoral resection was remarkable for an intermediate-grade chondrosarcomatous component juxtaposed to an area composed of anastomosing nests and cords of malignant epithelial cells showing nuclear atypia and increased mitotic activity. A fibroblastic-appearing spindle cell population was intimately associated with the epithelial cells. The epithelial cells labeled with 34bE12, AE1/AE3, EMA, and Vimentin (both spindled and epithelial components) while being negative for prostate-specific antigen, prostate specific acid phosphatase, cytokeratin 20, thyroid transcription factor-1, and CDX2. The patient developed local recurrence 9 months after the initial resection but has had no metastatic disease and consistently undetectable prostate-specific antigen levels. Deep parallel sequencing of the dedifferentiated component showed a nonsynonymous mutation at exon 4 of IDH1 gene at codon R132 leading to a substitution of arginine, with serine confirming glandular differentiation in dedifferentiated chondrosarcoma. Copyright © 2015 Elsevier Inc. All rights reserved.

Implementation of High-Dose-Rate Brachytherapy and Androgen Deprivation in Patients With Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lilleby, Wolfgang, E-mail: wolfgang.lilleby@ous-hf.no; Tafjord, Gunnar; Raabe, Nils K.

2012-07-01

Purpose: To evaluate outcome (overall survival [OS], the actuarial 5-year cancer-specific survival [CSS], disease-free survival [DFS], biochemical failure-free survival [BFS]), complications and morbidity in patients treated with high-dose-rate brachytherapy (HDR-BT) boost and hormonal treatment with curative aims. Methods: Between 2004 and 2009, 275 prospectively followed pN0/N0M0 patients were included: 19 patients (7%) with T2, Gleason score 7 and prostate-specific antigen (PSA) <10 and 256 patients (93%) with T3 or Gleason score 8-10 or PSA >20 received multimodal treatment with conformal four-field radiotherapy (prostate/vesiculae 2 Gy Multiplication-Sign 25) combined with HDR-BT (iridium 192; prostate 10 Gy Multiplication-Sign 2) with long-term androgenmore » deprivation therapy (ADT). Results: After a median observation time of 44.2 months (range, 10.4-90.5 months) 12 patients had relapsed clinically and/or biochemically and 10 patients were dead, of which 2 patients died from prostate cancer. Five-year estimates of BFS, CSS, DFS, and OS rates were 98.5%, 99.3%, 95.6%, and 96.3%, respectively. None of the patients with either Gleason score <8 or with intermediate risk profile had relapsed. The number of HDR-BT treatments was not related to outcome. Despite of age (median, 65.7 years; range, 45.7-77 years) and considerable pretreatment comorbidity in 39 of 275 patients, Genitourinary treatment-related morbidity was moderate with long-lasting Radiation Therapy Oncology Group Grade 2 voiding problems in 26 patients (9.5%) and occasionally mucous discharge in 20 patients (7%), none with Grade >2 for gastrointestinal at follow-up. Complications during implantations were related to pubic arch interference (4 patients) and lithotomy time, causing 2 patients to develop compartment syndrome. Conclusion: Despite still preliminary observations, our 5-year outcome estimates favor the implementation of high-dose-rate brachytherapy in high-risk patients combined with conformal external radiotherapy and long-term ADT. High-quality implants can be achieved by a trained specialized team at a high-turnover center using transrectal ultrasound-based treatment plans with acceptable morbidity and complication rates.« less

External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, Eunpi; Fred Hutchinson Cancer Research Center, Seattle, Washington; Mostaghel, Elahe A.

Purpose: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and Materials: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at themore » discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression. Preliminary analysis of the clinical data is also promising, with excellent PSA nadir and no relapse to date in this high-risk population.« less

Transrectal real-time elastography of the prostate: Normal patterns

PubMed Central

Goddi, A.; Sacchi, A.; Magistretti, G.; Almolla, J.

2011-01-01

Introduction Given the growing importance in clinical practice of transrectal real-time sonoelastography of the prostate, it is important to define normal patterns correlated to volume growth and reconsider the technical problems. Materials and methods We selected a sample of 100 men aged 30 to 87 with prostate volumes ranging from 20 to 100 cc. Strain images were obtained using an end-fire convex probe. The elasticity patterns of the various anatomical zones of the prostate were compared with the volume. Results The peripheral zone showed intermediate elasticity in 100% of cases regardless of the volume. We found some rare small areas of more limited elasticity in 23% of cases, among patients over 40. The posterior side of the central zone exhibited intermediate elasticity, and relative inelasticity was observed on the lateral side and at the base in 79% of cases. The entire central zone appeared compliant in 15% of cases and inelastic in 6%. The transition zone findings were stratified according to gland volume. When the volume was less than 45 cc, the transition zone was elastic in 67% of cases, inhomogeneously inelastic in 22%, and uniformly inelastic in 11%. In glands larger than 45 cc, the appearance was mainly elastic in 31% of cases, inhomogeneously inelastic in 57%, and uniformly inelastic in 12%. Conclusions Real-time elastography can distinguish the elastic properties of the prostate and define the normal patterns associated with increases in gland volume. PMID:23396618

Patient-reported outcomes following stereotactic body radiation therapy for clinically localized prostate cancer

PubMed Central

2014-01-01

Background Stereotactic body radiation therapy (SBRT) delivers high doses of radiation to the prostate while minimizing radiation to adjacent normal tissues. Large fraction sizes may increase the risk of functional decrements. Treatment-related bother may be more important to a patient than treatment-related dysfunction. This study reports on patient-reported outcomes following SBRT for clinically localized prostate cancer. Methods Between August 2007 and July 2011, 228 consecutive hormone-naïve patients with clinically localized prostate cancer were treated with 35–36.25 Gy SBRT delivered using the CyberKnife Radiosurgical System (Accuray) in 5 fractions. Quality of life was assessed using the American Urological Association Symptom Score (AUA) and the Expanded Prostate Cancer Index Composite (EPIC)-26. Urinary symptom flare was defined as an AUA score 15 or more with an increase of 5 or more points above baseline 6 months after treatment. Results 228 patients (88 low-, 126 intermediate- and 14 high-risk) at a median age of 69 (44–90) years received SBRT with a minimum follow-up of 24 months. EPIC urinary and bowel summary scores declined transiently at 1 month and experienced a second, more protracted decline between 9 months and 18 months before returning to near baseline 2 years post-SBRT. 14.5% of patients experienced late urinary symptom flare following treatment. Patients who experienced urinary symptom flare had poorer bowel quality of life following SBRT. EPIC scores for urinary bother declined transiently, first at 1 month and again at 12 months, before approaching pre-treatment scores by 2 years. Bowel bother showed a similar pattern, but the second decline was smaller and lasted 9 months to 18 months. EPIC sexual summary and bother scores progressively declined over the 2 years following SBRT without recovery. Conclusions In the first 2 years, the impact of SBRT on urination and defecation was minimal. Transient late increases in urinary and bowel dysfunction and bother were observed. However, urinary and bowel function and bother recovered to near baseline by 2 years post-SBRT. Sexual dysfunction and bother steadily increased following treatment without recovery. SBRT for clinically localized prostate cancer was well tolerated with treatment-related dysfunction and bother comparable to conventionally fractionated radiation therapy or brachytherapy. PMID:24512837

Green and black tea intake in relation to prostate cancer risk among Singapore Chinese

PubMed Central

Montague, Julia A.; Wu, Anna H.; Genkinger, Jeanine M.; Koh, Woon-Puay; Wong, Alvin S.; Wang, Renwei; Yuan, Jian-Min; Yu, Mimi C.

2013-01-01

Purpose Tea is one of the most commonly consumed beverages worldwide. To date, observational data from prospective cohort studies investigating the relationship between green and black tea intake and prostate cancer risk are sparse and equivocal. In a population-based, prospective cohort study of Chinese men in Singapore, we investigated the relationship between green and black tea intake and prostate cancer risk. Methods Tea consumption data for 27,293 men were collected at baseline (between 1993 and 1998) using a validated food frequency questionnaire. After an average of 11.2 years of follow-up, 298 men had developed prostate cancer. Proportional hazards regression methods were used to assess the associations between tea intake and prostate cancer risk. Results There was no association between daily green tea intake and prostate cancer risk, compared with no green tea intake [hazard ratio (HR) = 1.08; 95 % confidence interval (CI) 0.79, 1.47]. For black tea, a statistically significant positive association and trend were observed for daily intake compared with no black tea intake (HR = 1.41, 95 % CI 1.03, 1.92; p for trend <0.01) Conclusions Few prospective data are available from populations that have both a high level and wide range of black and green tea intake; this study represents a unique opportunity to evaluate their individual effects on prostate cancer risk. Our findings support the notion that green tea intake does not protect against prostate cancer and that black tea intake may increase prostate cancer risk. PMID:22864870

Green and black tea intake in relation to prostate cancer risk among Singapore Chinese.

PubMed

Montague, Julia A; Butler, Lesley M; Wu, Anna H; Genkinger, Jeanine M; Koh, Woon-Puay; Wong, Alvin S; Wang, Renwei; Yuan, Jian-Min; Yu, Mimi C

2012-10-01

Tea is one of the most commonly consumed beverages worldwide. To date, observational data from prospective cohort studies investigating the relationship between green and black tea intake and prostate cancer risk are sparse and equivocal. In a population-based, prospective cohort study of Chinese men in Singapore, we investigated the relationship between green and black tea intake and prostate cancer risk. Tea consumption data for 27,293 men were collected at baseline (between 1993 and 1998) using a validated food frequency questionnaire. After an average of 11.2 years of follow-up, 298 men had developed prostate cancer. Proportional hazards regression methods were used to assess the associations between tea intake and prostate cancer risk. There was no association between daily green tea intake and prostate cancer risk, compared with no green tea intake [hazard ratio (HR) = 1.08; 95 % confidence interval (CI) 0.79, 1.47]. For black tea, a statistically significant positive association and trend were observed for daily intake compared with no black tea intake (HR = 1.41, 95 % CI 1.03, 1.92; p for trend <0.01) Few prospective data are available from populations that have both a high level and wide range of black and green tea intake; this study represents a unique opportunity to evaluate their individual effects on prostate cancer risk. Our findings support the notion that green tea intake does not protect against prostate cancer and that black tea intake may increase prostate cancer risk.

Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer

DTIC Science & Technology

2017-10-01

SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer (PCA) is a clinically and genetically heterogeneous and the development of a molecular classification is...AWARD NUMBER: W81XWH-16-1-0739 TITLE: Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer PRINCIPAL...AND SUBTITLE 5a. CONTRACT NUMBER Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer 5b. GRANT NUMBER W81XWH

Selenium- or vitamin E-related gene variants, interaction with supplementation, and risk of high-grade prostate cancer in SELECT

PubMed Central

Chan, June M.; Darke, Amy K.; Penney, Kathryn L.; Tangen, Catherine M.; Goodman, Phyllis J.; Lee, Gwo-Shu Mary; Sun, Tong; Peisch, Sam; Tinianow, Alex M.; Rae, James M.; Klein, Eric A.; Thompson, Ian M.

2016-01-01

Background Epidemiological studies and secondary analyses of randomized trials supported the hypothesis that selenium and vitamin E lower prostate cancer risk. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no benefit of either supplement. Genetic variants involved in selenium or vitamin E metabolism or transport may underlie the complex associations of selenium and vitamin E. Methods We undertook a case-cohort study of SELECT participants randomized to placebo, selenium or vitamin E. The subcohort included 1,434 men; our primary outcome was high-grade prostate cancer (N=278 cases, Gleason 7 or higher cancer). We used weighted Cox regression to examine the association between SNPs and high-grade prostate cancer risk. To assess effect modification, we created interaction terms between randomization arm and genotype and calculated log likelihood statistics. Results We noted statistically significant (p<0.05) interactions between selenium assignment, SNPs in CAT, SOD2, PRDX6, SOD3, and TXNRD2 and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included SEC14L2, SOD1, and TTPA. In the placebo arm, several SNPs, hypothesized to interact with supplement assignment and risk of high-grade prostate cancer, were also directly associated with outcome. Conclusion Variants in selenium and vitamin E metabolism/transport genes may influence risk of overall and high-grade prostate cancer, and may modify an individual man’s response to vitamin E or selenium supplementation with regards to these risks. Impact The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. PMID:27197287

Perinatal and childhood factors and risk of prostate cancer in adulthood: MCC-Spain case-control study.

PubMed

Lope, Virginia; García-Esquinas, Esther; Ruiz-Dominguez, José Manuel; LLorca, Javier; Jiménez-Moleón, José Juan; Ruiz-Cerdá, José L; Alguacil, Juan; Tardón, Adonina; Dierssen-Sotos, Trinidad; Tabernero, Ángel; Mengual, Lourdes; Kogevinas, Manolis; Aragonés, Nuria; Castaño-Vinyals, Gemma; Pollán, Marina; Pérez-Gómez, Beatriz

2016-08-01

In utero and early-life exposures are suspected to modulate the risk of prostate cancer. This study examines the influence of certain perinatal and childhood-related factors on prostate cancer risk overall and by Gleason score at biopsy. MCC-Spain is a multicase-control study where 1088 histologically-confirmed incident prostate cancer cases (aged 42-85years) and 1345 population-based controls (aged 38-85years), frequency matched by age and province of recruitment, were recruited in 7 Spanish provinces. Self-reported perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with prostate cancer risk, globally and according to Gleason score at biopsy, was evaluated using logistic and multinomial regression mixed models, adjusting for age, family history of prostate cancer, educational level and body mass index one year before the interview, and including the province as a random effect term. Most perinatal factors were not related to prostate cancer risk, with the exception of middle-high socioeconomic level at birth (OR for high grade tumors=1.36; 95%CI=1.09-1.68). Regarding puberty, risk rose by 6% for each year of delayed onset (OR=1.06; 95%CI=1.01-1.10; p trend=0.016), with a clear excess of risk in men who reached puberty after age 15 (OR:1.35; 95%CI=1.08-1.68). A borderline significant positive association with prepubertal height was also observed (p trend=0.094). Some exposures experienced in utero and during adolescence, when the prostate is still maturing, might be relevant for prostate cancer risk in adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Incorporating Known Genetic Variants Does Not Improve the Accuracy of PSA Testing to Identify High Risk Prostate Cancer on Biopsy

PubMed Central

Gilbert, Rebecca; Martin, Richard M.; Evans, David M.; Tilling, Kate; Davey Smith, George; Kemp, John P.; Lane, J. Athene; Hamdy, Freddie C.; Neal, David E.; Donovan, Jenny L.; Metcalfe, Chris

2015-01-01

Introduction Prostate-specific antigen (PSA) testing is a widely accepted screening method for prostate cancer, but with low specificity at thresholds giving good sensitivity. Previous research identified four single nucleotide polymorphisms (SNPs) principally associated with circulating PSA levels rather than with prostate cancer risk (TERT rs2736098, FGFR2 rs10788160, TBX3 rs11067228, KLK3 rs17632542). Removing the genetic contribution to PSA levels may improve the ability of the remaining biologically-determined variation in PSA to discriminate between high and low risk of progression within men with identified prostate cancer. We investigate whether incorporating information on the PSA-SNPs improves the discrimination achieved by a single PSA threshold in men with raised PSA levels. Materials and Methods Men with PSA between 3-10ng/mL and histologically-confirmed prostate cancer were categorised as high or low risk of progression (Low risk: Gleason score≤6 and stage T1-T2a; High risk: Gleason score 7–10 or stage T2C). We used the combined genetic effect of the four PSA-SNPs to calculate a genetically corrected PSA risk score. We calculated the Area under the Curve (AUC) to determine how well genetically corrected PSA risk scores distinguished men at high risk of progression from low risk men. Results The analysis includes 868 men with prostate cancer (Low risk: 684 (78.8%); High risk: 184 (21.2%)). Receiver operating characteristic (ROC) curves indicate that including the 4 PSA-SNPs does not improve the performance of measured PSA as a screening tool for high/low risk prostate cancer (measured PSA level AU C = 59.5% (95% CI: 54.7,64.2) vs additionally including information from the 4 PSA-SNPs AUC = 59.8% (95% CI: 55.2,64.5) (p-value = 0.40)). Conclusion We demonstrate that genetically correcting PSA for the combined genetic effect of four PSA-SNPs, did not improve discrimination between high and low risk prostate cancer in men with raised PSA levels (3-10ng/mL). Replication and gaining more accurate estimates of the effects of the 4 PSA-SNPs and additional variants associated with PSA levels and not prostate cancer could be obtained from subsequent GWAS from larger prospective studies. PMID:26431041

Polymorphisms of Estrogen Metabolism-Related Genes and Prostate Cancer Risk in Two Populations of African Ancestry

PubMed Central

Emeville, Elise; Ferdinand, Séverine; Punga, Augustin; Lufuma, Simon; Blanchet, Pascal; Romana, Marc; Multigner, Luc

2016-01-01

Background Estrogens are thought to play a critical role in prostate carcinogenesis. It has been suggested that polymorphisms of genes encoding enzymes involved in estrogen metabolism are risk factors for prostate cancer. However, few studies have been performed on populations of African ancestry, which are known to have a high risk of prostate cancer. Objective We investigated whether functional polymorphisms of CYP17, CYP19, CYP1B1, COMT and UGT1A1 affected the risk of prostate cancer in two different populations of African ancestry. Methods In Guadeloupe (French West Indies), we compared 498 prostate cancer patients and 565 control subjects. In Kinshasa (Democratic Republic of Congo), 162 prostate cancer patients were compared with 144 controls. Gene polymorphisms were determined by the SNaPshot technique or short tandem repeat PCR analysis. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results The AA genotype and the A allele of rs4680 (COMT) appeared to be inversely associated with the risk of prostate cancer in adjusted models for both Afro-Caribbean and native African men. For the A allele, a significant inverse association was observed among cases with low-grade Gleason scores and localized clinical stage, in both populations. Conclusions These preliminary results support the hypothesis that polymorphisms of genes encoding enzymes involved in estrogen metabolism may modulate the risk of prostate cancer in populations of African ancestry. PMID:27074016

Use of advanced treatment technologies among men at low risk of dying from prostate cancer.

PubMed

Jacobs, Bruce L; Zhang, Yun; Schroeck, Florian R; Skolarus, Ted A; Wei, John T; Montie, James E; Gilbert, Scott M; Strope, Seth A; Dunn, Rodney L; Miller, David C; Hollenbeck, Brent K

2013-06-26

The use of advanced treatment technologies (ie, intensity-modulated radiotherapy [IMRT] and robotic prostatectomy) for prostate cancer is increasing. The extent to which these advanced treatment technologies have disseminated among patients at low risk of dying from prostate cancer is uncertain. To assess the use of advanced treatment technologies, compared with prior standards (ie, traditional external beam radiation treatment [EBRT] and open radical prostatectomy) and observation, among men with a low risk of dying from prostate cancer. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified a retrospective cohort of men diagnosed with prostate cancer between 2004 and 2009 who underwent IMRT (n = 23,633), EBRT (n = 3926), robotic prostatectomy (n = 5881), open radical prostatectomy (n = 6123), or observation (n = 16,384). Follow-up data were available through December 31, 2010. The use of advanced treatment technologies among men unlikely to die from prostate cancer, as assessed by low-risk disease (clinical stage ≤T2a, biopsy Gleason score ≤6, and prostate-specific antigen level ≤10 ng/mL), high risk of noncancer mortality (based on the predicted probability of death within 10 years in the absence of a cancer diagnosis), or both. In our cohort, the use of advanced treatment technologies increased from 32% (95% CI, 30%-33%) to 44% (95% CI, 43%-46%) among men with low-risk disease (P < .001) and from 36% (95% CI, 35%-38%) to 57% (95% CI, 55%-59%) among men with high risk of noncancer mortality (P < .001). The use of these advanced treatment technologies among men with both low-risk disease and high risk of noncancer mortality increased from 25% (95% CI, 23%-28%) to 34% (95% CI, 31%-37%) (P < .001). Among all patients diagnosed in SEER, the use of advanced treatment technologies for men unlikely to die from prostate cancer increased from 13% (95% CI, 12%-14%), or 129.2 per 1000 patients diagnosed with prostate cancer, to 24% (95% CI, 24%-25%), or 244.2 per 1000 patients diagnosed with prostate cancer (P < .001). Among men diagnosed with prostate cancer between 2004 and 2009 who had low-risk disease, high risk of noncancer mortality, or both, the use of advanced treatment technologies has increased.

Investigative clinical study on prostate cancer part VI: Follicle-stimulating hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population.

PubMed

Porcaro, Antonio B; Migliorini, Filippo; Petrozziello, Aldo; Sava, Teodoro; Romano, Mario; Caruso, Beatrice; Cocco, Claudio; Ghimenton, Claudio; Zecchinini Antoniolli, Stefano; Lacola, Vincenzo; Rubilotta, Emanuele; Monaco, Carmelo; Comunale, Luigi

2012-01-01

To evaluate the physiopathology of follicle-stimulating hormone (FSH) along the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population. The study included 98 patients who were diagnosed with prostate cancer. Age, percentages of positive cores (P+) at transrectal ultrasound scan biopsy, biopsy Gleason score (bGS), luteinizing hormone (LH), FSH, total testosterone, free testosterone (FT) and prostate-specific antigen (PSA) were the continuous clinical variables. All patients had not previously received hormonal manipulations. FSH correlation and multiple linear analyses were computed in the population. The FSH/PSA ratio was computed and then ranked for clustering the population as groups A (0.13≤FSH/PSA≤0.57), B (0.57

Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

PubMed Central

Lecarpentier, Julie; Silvestri, Valentina; Kuchenbaecker, Karoline B.; Barrowdale, Daniel; Dennis, Joe; McGuffog, Lesley; Soucy, Penny; Leslie, Goska; Rizzolo, Piera; Navazio, Anna Sara; Valentini, Virginia; Zelli, Veronica; Lee, Andrew; Amin Al Olama, Ali; Tyrer, Jonathan P.; Southey, Melissa; John, Esther M.; Conner, Thomas A.; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Steele, Linda; Ding, Yuan Chun; Neuhausen, Susan L.; Hansen, Thomas V.O.; Osorio, Ana; Weitzel, Jeffrey N.; Toss, Angela; Medici, Veronica; Cortesi, Laura; Zanna, Ines; Palli, Domenico; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Azzollini, Jacopo; Viel, Alessandra; Cini, Giulia; Damante, Giuseppe; Tommasi, Stefania; Peterlongo, Paolo; Fostira, Florentia; Hamann, Ute; Evans, D. Gareth; Henderson, Alex; Brewer, Carole; Eccles, Diana; Cook, Jackie; Ong, Kai-ren; Walker, Lisa; Side, Lucy E.; Porteous, Mary E.; Davidson, Rosemarie; Hodgson, Shirley; Frost, Debra; Adlard, Julian; Izatt, Louise; Eeles, Ros; Ellis, Steve; Tischkowitz, Marc; Godwin, Andrew K.; Meindl, Alfons; Gehrig, Andrea; Dworniczak, Bernd; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Hahnen, Eric; Hauke, Jan; Rhiem, Kerstin; Kast, Karin; Arnold, Norbert; Ditsch, Nina; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Wand, Dorothea; Lasset, Christine; Stoppa-Lyonnet, Dominique; Belotti, Muriel; Damiola, Francesca; Barjhoux, Laure; Mazoyer, Sylvie; Van Heetvelde, Mattias; Poppe, Bruce; De Leeneer, Kim; Claes, Kathleen B.M.; de la Hoya, Miguel; Garcia-Barberan, Vanesa; Caldes, Trinidad; Perez Segura, Pedro; Kiiski, Johanna I.; Aittomäki, Kristiina; Khan, Sofia; Nevanlinna, Heli; van Asperen, Christi J.; Vaszko, Tibor; Kasler, Miklos; Olah, Edith; Balmaña, Judith; Gutiérrez-Enríquez, Sara; Diez, Orland; Teulé, Alex; Izquierdo, Angel; Darder, Esther; Brunet, Joan; Del Valle, Jesús; Feliubadalo, Lidia; Pujana, Miquel Angel; Lazaro, Conxi; Arason, Adalgeir; Agnarsson, Bjarni A.; Johannsson, Oskar Th.; Barkardottir, Rosa B.; Alducci, Elisa; Tognazzo, Silvia; Montagna, Marco; Teixeira, Manuel R.; Pinto, Pedro; Spurdle, Amanda B.; Holland, Helene; Lee, Jong Won; Lee, Min Hyuk; Lee, Jihyoun; Kim, Sung-Won; Kang, Eunyoung; Kim, Zisun; Sharma, Priyanka; Rebbeck, Timothy R.; Vijai, Joseph; Robson, Mark; Lincoln, Anne; Musinsky, Jacob; Gaddam, Pragna; Tan, Yen Y.; Berger, Andreas; Singer, Christian F.; Loud, Jennifer T.; Greene, Mark H.; Mulligan, Anna Marie; Glendon, Gord; Andrulis, Irene L.; Toland, Amanda Ewart; Senter, Leigha; Bojesen, Anders; Nielsen, Henriette Roed; Skytte, Anne-Bine; Sunde, Lone; Jensen, Uffe Birk; Pedersen, Inge Sokilde; Krogh, Lotte; Kruse, Torben A.; Caligo, Maria A.; Yoon, Sook-Yee; Teo, Soo-Hwang; von Wachenfeldt, Anna; Huo, Dezheng; Nielsen, Sarah M.; Olopade, Olufunmilayo I.; Nathanson, Katherine L.; Domchek, Susan M.; Lorenchick, Christa; Jankowitz, Rachel C.; Campbell, Ian; James, Paul; Mitchell, Gillian; Orr, Nick; Park, Sue Kyung; Thomassen, Mads; Offit, Kenneth; Couch, Fergus J.; Simard, Jacques; Easton, Douglas F.; Chenevix-Trench, Georgia; Schmutzler, Rita K.; Antoniou, Antonis C.; Ottini, Laura

2017-01-01

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated—for the first time to our knowledge—associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10−6). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10−9). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management. PMID:28448241

Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores.

PubMed

Lecarpentier, Julie; Silvestri, Valentina; Kuchenbaecker, Karoline B; Barrowdale, Daniel; Dennis, Joe; McGuffog, Lesley; Soucy, Penny; Leslie, Goska; Rizzolo, Piera; Navazio, Anna Sara; Valentini, Virginia; Zelli, Veronica; Lee, Andrew; Amin Al Olama, Ali; Tyrer, Jonathan P; Southey, Melissa; John, Esther M; Conner, Thomas A; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Steele, Linda; Ding, Yuan Chun; Neuhausen, Susan L; Hansen, Thomas V O; Osorio, Ana; Weitzel, Jeffrey N; Toss, Angela; Medici, Veronica; Cortesi, Laura; Zanna, Ines; Palli, Domenico; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Azzollini, Jacopo; Viel, Alessandra; Cini, Giulia; Damante, Giuseppe; Tommasi, Stefania; Peterlongo, Paolo; Fostira, Florentia; Hamann, Ute; Evans, D Gareth; Henderson, Alex; Brewer, Carole; Eccles, Diana; Cook, Jackie; Ong, Kai-Ren; Walker, Lisa; Side, Lucy E; Porteous, Mary E; Davidson, Rosemarie; Hodgson, Shirley; Frost, Debra; Adlard, Julian; Izatt, Louise; Eeles, Ros; Ellis, Steve; Tischkowitz, Marc; Godwin, Andrew K; Meindl, Alfons; Gehrig, Andrea; Dworniczak, Bernd; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Hahnen, Eric; Hauke, Jan; Rhiem, Kerstin; Kast, Karin; Arnold, Norbert; Ditsch, Nina; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Wand, Dorothea; Lasset, Christine; Stoppa-Lyonnet, Dominique; Belotti, Muriel; Damiola, Francesca; Barjhoux, Laure; Mazoyer, Sylvie; Van Heetvelde, Mattias; Poppe, Bruce; De Leeneer, Kim; Claes, Kathleen B M; de la Hoya, Miguel; Garcia-Barberan, Vanesa; Caldes, Trinidad; Perez Segura, Pedro; Kiiski, Johanna I; Aittomäki, Kristiina; Khan, Sofia; Nevanlinna, Heli; van Asperen, Christi J; Vaszko, Tibor; Kasler, Miklos; Olah, Edith; Balmaña, Judith; Gutiérrez-Enríquez, Sara; Diez, Orland; Teulé, Alex; Izquierdo, Angel; Darder, Esther; Brunet, Joan; Del Valle, Jesús; Feliubadalo, Lidia; Pujana, Miquel Angel; Lazaro, Conxi; Arason, Adalgeir; Agnarsson, Bjarni A; Johannsson, Oskar Th; Barkardottir, Rosa B; Alducci, Elisa; Tognazzo, Silvia; Montagna, Marco; Teixeira, Manuel R; Pinto, Pedro; Spurdle, Amanda B; Holland, Helene; Lee, Jong Won; Lee, Min Hyuk; Lee, Jihyoun; Kim, Sung-Won; Kang, Eunyoung; Kim, Zisun; Sharma, Priyanka; Rebbeck, Timothy R; Vijai, Joseph; Robson, Mark; Lincoln, Anne; Musinsky, Jacob; Gaddam, Pragna; Tan, Yen Y; Berger, Andreas; Singer, Christian F; Loud, Jennifer T; Greene, Mark H; Mulligan, Anna Marie; Glendon, Gord; Andrulis, Irene L; Toland, Amanda Ewart; Senter, Leigha; Bojesen, Anders; Nielsen, Henriette Roed; Skytte, Anne-Bine; Sunde, Lone; Jensen, Uffe Birk; Pedersen, Inge Sokilde; Krogh, Lotte; Kruse, Torben A; Caligo, Maria A; Yoon, Sook-Yee; Teo, Soo-Hwang; von Wachenfeldt, Anna; Huo, Dezheng; Nielsen, Sarah M; Olopade, Olufunmilayo I; Nathanson, Katherine L; Domchek, Susan M; Lorenchick, Christa; Jankowitz, Rachel C; Campbell, Ian; James, Paul; Mitchell, Gillian; Orr, Nick; Park, Sue Kyung; Thomassen, Mads; Offit, Kenneth; Couch, Fergus J; Simard, Jacques; Easton, Douglas F; Chenevix-Trench, Georgia; Schmutzler, Rita K; Antoniou, Antonis C; Ottini, Laura

2017-07-10

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10 -6 ). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10 -9 ). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

African American men with low-grade prostate cancer have increased disease recurrence after prostatectomy compared with Caucasian men.

PubMed

Yamoah, Kosj; Deville, Curtiland; Vapiwala, Neha; Spangler, Elaine; Zeigler-Johnson, Charnita M; Malkowicz, Bruce; Lee, David I; Kattan, Michael; Dicker, Adam P; Rebbeck, Timothy R

2015-02-01

To explore whether disparities in outcomes exist between African American (AA) and Caucasian (CS) men with low-grade prostate cancer and similar cancer of the prostate risk assessment-postsurgery (CAPRA-S) features following prostatectomy (RP). The overall cohort consisted of 1,265 men (234 AA and 1,031 CS) who met the National comprehensive cancer network criteria for low- to intermediate-risk prostate cancer and underwent RP between 1990 and 2012. We first evaluated whether clinical factors were associated with adverse pathologic outcomes and freedom from biochemical failure (FFbF) using the entire cohort. Next, we studied a subset of 705 men (112 AA and 593 CS) who had pathologic Gleason score≤6 (low-grade disease). Using this cohort, we determined whether race affected FFbF in men with RP-proven low-grade disease and similar CAPRA-S scores. With a median follow-up time of 27 months, the overall 7-year FFbF rate was 86% vs. 79% in CS and AA men, respectively (P = 0.035). There was no significant difference in one or more adverse pathologic features between CS vs. AA men (27% vs. 31%; P = 0.35) or CAPRA-S score (P = 0.28). In the subset analysis of patients with low-grade disease, AA race was associated with worse FFbF outcomes (P = 0.002). Furthermore, AA race was a significant predictor of FFbF in men with low-grade disease (hazard ratio = 2.01, 95% CI: 1.08-3.72; P = 0.029). AA race is a predictor of worse FFbF outcomes in men with low-grade disease after RP. These results suggest that a subset of AA men with low-grade disease may benefit from more aggressive treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men.

PubMed

Sjoberg, Daniel D; Vickers, Andrew J; Assel, Melissa; Dahlin, Anders; Poon, Bing Ying; Ulmert, David; Lilja, Hans

2018-06-01

Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Prostate cancer death (n=317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of <7.5%, translating into 1.7% risk of prostate cancer death at 15 yr-a similar estimate to that of a man with a PSA of 1.6ng/ml. Men with a four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Non-dietary environmental risk factors in prostate cancer

PubMed Central

Ferrís-i-Tortajada, J; Berbel-Tornero, O; Garcia-i-Castell, J; López-Andreu, J.A.; Sobrino-Najul, E; Ortega-García, J.A.

2016-01-01

Introduction The aim is to update and disclose the main environmental risk factors, excluding dietary factors, involved in the etiopathology of prostate cancer. Materials and methods Bibliographic review of the last 25 years of non-dietary environmental risk factors associated with prostate cancer between 1985 and 2010, obtained from MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Environmental Risk Factors/Tobacco/Infectious-Inflammatory Factors/Pesticides/Vasectomy/Occupational Exposures/ Chemoprevention Agents/Radiation and Prostate Cancer. Results While some non-dietary environmental risk factors increase the risk of acquiring the disease, others decrease it. Of the former, it is worth mentioning exposal to tobacco smoke, chronic infectious-inflammatory prostatic processes and occupational exposure to cadmium, herbicides and pesticides. The first factors that reduce the risk are the use of chemopreventive drugs (Finasterida, Dutasteride) and exposure to ultraviolet solar radiation. With the current data, a vasectomy does not influence the risk of developing the disease. Conclusions The slow process of prostate carcinogenesis is the final result of the interaction of constitutional risk and environmental factors. Non-dietary environmental factors play an important role in the etiopathology of this disease. To appropriately assess the risk factors, extensive case studies that include all the possible variables must be analyzed. PMID:21439685

Estimating preferences for treatments in patients with localized prostate cancer.

PubMed

Ávila, Mónica; Becerra, Virginia; Guedea, Ferran; Suárez, José Francisco; Fernandez, Pablo; Macías, Víctor; Mariño, Alfonso; Hervás, Asunción; Herruzo, Ismael; Ortiz, María José; Ponce de León, Javier; Sancho, Gemma; Cunillera, Oriol; Pardo, Yolanda; Cots, Francesc; Ferrer, Montse

2015-02-01

Studies of patients' preferences for localized prostate cancer treatments have assessed radical prostatectomy and external radiation therapy, but none of them has evaluated brachytherapy. The aim of our study was to assess the preferences and willingness to pay of patients with localized prostate cancer who had been treated with radical prostatectomy, external radiation therapy, or brachytherapy, and their related urinary, sexual, and bowel side effects. This was an observational, prospective cohort study with follow-up until 5 years after treatment. A total of 704 patients with low or intermediate risk localized prostate cancer were consecutively recruited from 2003 to 2005. The estimation of preferences was conducted using time trade-off, standard gamble, and willingness-to-pay methods. Side effects were measured with the Expanded Prostate Index Composite (EPIC), a prostate cancer-specific questionnaire. Tobit models were constructed to assess the impact of treatment and side effects on patients' preferences. Propensity score was applied to adjust for treatment selection bias. Of the 580 patients reporting preferences, 165 were treated with radical prostatectomy, 152 with external radiation therapy, and 263 with brachytherapy. Both time trade-off and standard gamble results indicated that the preferences of patients treated with brachytherapy were 0.06 utilities higher than those treated with radical prostatectomy (P=.01). Similarly, willingness-to-pay responses showed a difference of €57/month (P=.004) between these 2 treatments. Severe urinary incontinence presented an independent impact on the preferences elicited (P<.05), whereas no significant differences were found by bowel and sexual side effects. Our findings indicate that urinary incontinence is the side effect with the highest impact on preferences and that brachytherapy and external radiation therapy are more valued than radical prostatectomy. These time trade-off and standard gamble preference assessments as well as the willingness-to-pay estimation could be useful to perform respectively cost-utility or cost-benefit analyses, which can guide health policy decisions. Copyright © 2015 Elsevier Inc. All rights reserved.

Estimating Preferences for Treatments in Patients With Localized Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ávila, Mónica; CIBER en Epidemiología y Salud Pública; Universitat Pompeu Fabra, Barcelona

Purpose: Studies of patients' preferences for localized prostate cancer treatments have assessed radical prostatectomy and external radiation therapy, but none of them has evaluated brachytherapy. The aim of our study was to assess the preferences and willingness to pay of patients with localized prostate cancer who had been treated with radical prostatectomy, external radiation therapy, or brachytherapy, and their related urinary, sexual, and bowel side effects. Methods and Materials: This was an observational, prospective cohort study with follow-up until 5 years after treatment. A total of 704 patients with low or intermediate risk localized prostate cancer were consecutively recruited from 2003more » to 2005. The estimation of preferences was conducted using time trade-off, standard gamble, and willingness-to-pay methods. Side effects were measured with the Expanded Prostate Index Composite (EPIC), a prostate cancer-specific questionnaire. Tobit models were constructed to assess the impact of treatment and side effects on patients' preferences. Propensity score was applied to adjust for treatment selection bias. Results: Of the 580 patients reporting preferences, 165 were treated with radical prostatectomy, 152 with external radiation therapy, and 263 with brachytherapy. Both time trade-off and standard gamble results indicated that the preferences of patients treated with brachytherapy were 0.06 utilities higher than those treated with radical prostatectomy (P=.01). Similarly, willingness-to-pay responses showed a difference of €57/month (P=.004) between these 2 treatments. Severe urinary incontinence presented an independent impact on the preferences elicited (P<.05), whereas no significant differences were found by bowel and sexual side effects. Conclusions: Our findings indicate that urinary incontinence is the side effect with the highest impact on preferences and that brachytherapy and external radiation therapy are more valued than radical prostatectomy. These time trade-off and standard gamble preference assessments as well as the willingness-to-pay estimation could be useful to perform respectively cost-utility or cost-benefit analyses, which can guide health policy decisions.« less

A functional variant in NKX3.1 associated with prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

PubMed Central

Martinez, Erin E.; Darke, Amy K.; Tangen, Catherine M.; Goodman, Phyllis J.; Fowke, Jay H.; Klein, Eric A.; Abdulkadir, Sarki A.

2014-01-01

NKX3.1 is an androgen-regulated prostate tumor suppressor protein. We previously found that antioxidant administration (N-acetylcysteine) in the Nkx3.1 knock-out mouse model promoted prostate epithelial proliferation, suggesting that NKX3.1 activity modifies the effect of antioxidant administration on prostate carcinogenesis. Interestingly, administration of the antioxidant vitamin E significantly increased prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), suggesting our animal experiments may be relevant to humans. To determine whether NKX3.1 played a role in increased human prostate cancer risk associated with antioxidant administration in SELECT, we investigated the joint risk of antioxidant administration and NKX3.1 genotypes previously found to be associated with decreased NKX3.1 mRNA expression (rs11781886) or DNA-binding activity in vitro (rs2228013) in the SELECT biomarker case-cohort sub-study (1,866 cases; 3135 non-cases). Multivariable COX regression models were developed to determine the joint association of NKX3.1 genotypes with administration of vitamin E, selenium, or the combination, compared to placebo. The CC genotype at rs11781886 combined with selenium administration was associated with increased overall prostate cancer risk (HR 1.676, 95% CI 1.011-2.777, p=0.045) and low grade prostate cancer risk (HR 1.811, 95% CI 1.016-3.228, p=0.0441). Similarly, the rs11781886 minor allele (CC+CT) combined with vitamin E administration was significantly associated with increased prostate cancer risk (HR 1.450, 95% CI 1.117-1.882, p=0.0052). Our results indicate that variation in NKX3.1 expression combined with selenium or vitamin E treatment modifies the risk of prostate cancer. Genetic background may modulate the effects of antioxidant supplementation thought to act as chemoprevention agents. PMID:24894197

Trichomonas vaginalis infection and risk of advanced prostate cancer.

PubMed

Shui, Irene M; Kolb, Suzanne; Hanson, Christi; Sutcliffe, Siobhan; Rider, Jennifer R; Stanford, Janet L

2016-05-01

The epidemiologic evidence for an association of Trichomonas vaginalis (Tv) with overall prostate cancer is mixed, but some studies suggest Tv may increase risk of more aggressive disease. The aim of this study was to assess whether Tv serostatus is associated with advanced or fatal prostate cancer. A total of 146 men with advanced (metastatic or fatal) prostate cancer and 181 age-matched controls were selected from two prior population-based, case-control studies. Tv serostatus was determined with the same laboratory methods used in previous epidemiologic studies. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression to compare Tv serostatus in prostate cancer cases and controls adjusted for potential confounders. The seroprevalence of Tv in controls was 23%. Tv serostatus was not associated with an increased risk of metastatic or fatal prostate cancer (ORs < 1). Our study does not support an increased risk of advanced or fatal prostate cancer in men seropositive for Tv. © 2016 Wiley Periodicals, Inc.

Whole-Pelvic Nodal Radiation Therapy in the Context of Hypofractionation for High-Risk Prostate Cancer Patients: A Step Forward

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaidar-Person, Orit; Roach, Mack; Créhange, Gilles, E-mail: gcrehange@cgfl.fr

2013-07-15

Given the low α/β ratio of prostate cancer, prostate hypofractionation has been tested through numerous clinical studies. There is a growing body of literature suggesting that with high conformal radiation therapy and even with more sophisticated radiation techniques, such as high-dose-rate brachytherapy or image-guided intensity modulated radiation therapy, morbidity associated with shortening overall treatment time with higher doses per fraction remains low when compared with protracted conventional radiation therapy to the prostate only. In high-risk prostate cancer patients, there is accumulating evidence that either dose escalation to the prostate or hypofractionation may improve outcome. Nevertheless, selected patients who have amore » high risk of lymph node involvement may benefit from whole-pelvic radiation therapy (WPRT). Although combining WPRT with hypofractionated prostate radiation therapy is feasible, it remains investigational. By combining modern advances in radiation oncology (high-dose-rate prostate brachytherapy, intensity modulated radiation therapy with an improved image guidance for soft-tissue sparing), it is hypothesized that WPRT could take advantage of recent results from hypofractionation trials. Moreover, the results from hypofractionation trials raise questions as to whether hypofractionation to pelvic lymph nodes with a high risk of occult involvement might improve the outcomes in WPRT. Although investigational, this review discusses the challenging idea of WPRT in the context of hypofractionation for patients with high-risk prostate cancer.« less

Analysis of recently identified prostate cancer susceptibility loci in a population-based study: Associations with family history and clinical features

PubMed Central

FitzGerald, Liesel M.; Kwon, Erika M.; Koopmeiners, Joseph S.; Salinas, Claudia A.; Stanford, Janet L.; Ostrander, Elaine A.

2009-01-01

Purpose Two recent genome-wide association studies have highlighted several SNPs purported to be associated with prostate cancer risk. We investigated the significance of these SNPs in a population-based study of Caucasian men, testing the effects of each SNP in relation to family history of prostate cancer and clinicopathological features of disease. Experimental Design We genotyped 13 SNPs in 1,308 prostate cancer patients and 1,267 unaffected controls frequency matched to cases by five-year age groups. The association of each SNP with disease risk and stratified by family history of prostate cancer and clinicopathological features of disease was calculated using logistic and polytomous regression. Results These results confirm the importance of multiple previously reported SNPs in relation to prostate cancer susceptibility; 11 of the 13 SNPs were significantly associated with risk of developing prostate cancer. However, none of the SNP associations were of comparable magnitude to that associated with having a first-degree family history of the disease. Risk estimates associated with SNPs rs4242382 and rs2735839 varied by family history, while risk estimates for rs10993994 and rs5945619 varied by Gleason score. Conclusions Our results confirm that several recently identified SNPs are associated with prostate cancer risk; however the variant alleles only confer a low to moderate relative risk of disease and are generally not associated with more aggressive disease features. PMID:19366831

Is there still a role for computed tomography and bone scintigraphy in prostate cancer staging? An analysis from the EUREKA-1 database.

PubMed

Gabriele, D; Collura, D; Oderda, M; Stura, I; Fiorito, C; Porpiglia, F; Terrone, C; Zacchero, M; Guiot, C; Gabriele, P

2016-04-01

According to the current guidelines, computed tomography (CT) and bone scintigraphy (BS) are optional in intermediate-risk and recommended in high-risk prostate cancer (PCa). We wonder whether it is time for these examinations to be dismissed, evaluating their staging accuracy in a large cohort of radical prostatectomy (RP) patients. To evaluate the ability of CT to predict lymph node involvement (LNI), we included 1091 patients treated with RP and pelvic lymph node dissection, previously staged with abdomino-pelvic CT. As for bone metastases, we included 1145 PCa patients deemed fit for surgery, previously staged with Tc-99m methylene diphosphonate planar BS. CT scan showed a sensitivity and specificity in predicting LNI of 8.8 and 98 %; subgroup analysis disclosed a significant association only for the high-risk subgroup of 334 patients (P 0.009) with a sensitivity of 11.8 % and positive predictive value (PPV) of 44.4 %. However, logistic multivariate regression analysis including preoperative risk factors excluded any additional predictive ability of CT even in the high-risk group (P 0.40). These data are confirmed by ROC curve analysis, showing a low AUC of 54 % for CT, compared with 69 % for Partin tables and 80 % for Briganti nomogram. BS showed some positivity in 74 cases, only four of whom progressed, while 49 patients with negative BS progressed during their follow-up, six of them immediately after surgery. According to our opinion, the role of CT and BS should be restricted to selected high-risk patients, while clinical predictive nomograms should be adopted for the surgical planning.

Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes.

PubMed

Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M; Aleixandre, Rosa N; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

2016-01-01

New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic.

Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes

PubMed Central

Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M.; Aleixandre, Rosa N.; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

2016-01-01

New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic. PMID:27279911

Prostate cancer and inflammation: the evidence

PubMed Central

Sfanos, Karen S; De Marzo, Angelo M

2014-01-01

Chronic inflammation is now known to contribute to several forms of human cancer, with an estimated 20% of adult cancers attributable to chronic inflammatory conditions caused by infectious agents, chronic noninfectious inflammatory diseases and / or other environmental factors. Indeed, chronic inflammation is now regarded as an ‘enabling characteristic’ of human cancer. The aim of this review is to summarize the current literature on the evidence for a role for chronic inflammation in prostate cancer aetiology, with a specific focus on recent advances regarding the following: (i) potential stimuli for prostatic inflammation; (ii) prostate cancer immunobiology; (iii) inflammatory pathways and cytokines in prostate cancer risk and development; (iv) proliferative inflammatory atrophy (PIA) as a risk factor lesion to prostate cancer development; and (v) the role of nutritional or other antiinflammatory compounds in reducing prostate cancer risk. PMID:22212087

Prostate specific antigen velocity does not aid prostate cancer detection in men with prior negative biopsy.

PubMed

Vickers, Andrew J; Wolters, Tineke; Savage, Caroline J; Cronin, Angel M; O'Brien, M Frank; Roobol, Monique J; Aus, Gunnar; Scardino, Peter T; Hugosson, Jonas; Schröder, Fritz H; Lilja, Hans

2010-09-01

Prostate specific antigen velocity has been proposed as a marker to aid in prostate cancer detection. We determined whether prostate specific antigen velocity could predict repeat biopsy results in men with persistently increased prostate specific antigen after initial negative biopsy. We identified 1,837 men who participated in the Göteborg or Rotterdam section of the European Randomized Screening study of Prostate Cancer and who underwent 1 or more subsequent prostate biopsies after an initial negative finding. We evaluated whether prostate specific antigen velocity improved predictive accuracy beyond that of prostate specific antigen alone. Of the 2,579 repeat biopsies 363 (14%) were positive for prostate cancer, of which 44 (1.7%) were high grade (Gleason score 7 or greater). Prostate specific antigen velocity was statistically associated with cancer risk but had low predictive accuracy (AUC 0.55, p <0.001). There was some evidence that prostate specific antigen velocity improved AUC compared to prostate specific antigen for high grade cancer. However, the small increase in risk associated with high prostate specific antigen velocity (from 1.7% to 2.8% as velocity increased from 0 to 1 ng/ml per year) had questionable clinical relevance. Men with prior negative biopsy are at lower risk for prostate cancer at subsequent biopsies with high grade disease particularly rare. We found little evidence to support prostate specific antigen velocity to aid in decisions about repeat biopsy for prostate cancer. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Modifiable Prostate Cancer Risk Reduction and Early Detection Behaviors in Black Men

ERIC Educational Resources Information Center

Odedina, Folakemi T.; Scrivens, John J., Jr.; Larose-Pierre, Margareth; Emanuel, Frank; Adams, Angela Denise; Dagne, Getachew A.; Pressey, Shannon Alexis; Odedina, Oladapo

2011-01-01

Objective: To explore the personal factors related to modifiable prostate cancer risk-reduction and detection behaviors among black men. Methods: Three thousand four hundred thirty (3430) black men were surveyed and structural equation modeling employed to test study hypotheses. Results: Modifiable prostate cancer risk-reduction behavior was found…

Sedentary behavior and prostate cancer risk in the NIH-AARP Diet and Health Study.

PubMed

Lynch, Brigid M; Friedenreich, Christine M; Kopciuk, Karen A; Hollenbeck, Albert R; Moore, Steven C; Matthews, Charles E

2014-05-01

Sedentary behavior (sitting time) has been proposed as an independent risk factor for some cancers; however, its role in the development of prostate cancer has not been determined. We examined the prospective associations of self-reported daily sitting time and daily television/video viewing time with the risk of developing or dying from prostate cancer among 170,481 men in the NIH-AARP Diet and Health Study. We estimated HRs and 95% confidence intervals (CI) using Cox proportional hazards regression. Between 1996 and 2006, there were 13,751 incident (including 1,365 advanced) prostate cancer cases identified; prostate cancer mortality (through 2008) was 669. No strong or significant association with prostate cancer risk was seen in fully adjusted models for either daily sitting or television/video time. There were some suggestions of effect modification by body mass index (BMI; interaction for television/video time and BMI, P = 0.02). For total prostate cancer risk, television/video time was associated with a slightly elevated, but nonsignificant, increase amongst obese men (HR = 1.28; 95% CI, 0.98-1.69); a null association was observed amongst overweight men (HR = 1.04; 0.89-1.22); and, for men with a normal BMI, television/video time was associated with a nonsignificant risk decrease (HR = 0.82; 95% CI, 0.66-1.01). Similar patterns were observed for total daily sitting and television/video time in advanced prostate cancer and prostate cancer mortality. Sedentary behavior seems to play a limited role in the development of prostate cancer; however, we cannot rule out potential effect modification by BMI or the impact of measurement error on results. ©2014 AACR.

Pretreatment Nomogram to Predict the Risk of Acute Urinary Retention After I-125 Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roeloffzen, Ellen M., E-mail: e.m.a.roeloffzen@umcutrecht.nl; Vulpen, Marco van; Battermann, Jan J.

Purpose: Acute urinary retention (AUR) after iodine-125 (I-125) prostate brachytherapy negatively influences long-term quality of life and therefore should be prevented. We aimed to develop a nomogram to preoperatively predict the risk of AUR. Methods: Using the preoperative data of 714 consecutive patients who underwent I-125 prostate brachytherapy between 2005 and 2008 at our department, we modeled the probability of AUR. Multivariate logistic regression analysis was used to assess the predictive ability of a set of pretreatment predictors and the additional value of a new risk factor (the extent of prostate protrusion into the bladder). The performance of the finalmore » model was assessed with calibration and discrimination measures. Results: Of the 714 patients, 57 patients (8.0%) developed AUR after implantation. Multivariate analysis showed that the combination of prostate volume, IPSS score, neoadjuvant hormonal treatment and the extent of prostate protrusion contribute to the prediction of AUR. The discriminative value (receiver operator characteristic area, ROC) of the basic model (including prostate volume, International Prostate Symptom Score, and neoadjuvant hormonal treatment) to predict the development of AUR was 0.70. The addition of prostate protrusion significantly increased the discriminative power of the model (ROC 0.82). Calibration of this final model was good. The nomogram showed that among patients with a low sum score (<18 points), the risk of AUR was only 0%-5%. However, in patients with a high sum score (>35 points), the risk of AUR was more than 20%. Conclusion: This nomogram is a useful tool for physicians to predict the risk of AUR after I-125 prostate brachytherapy. The nomogram can aid in individualized treatment decision-making and patient counseling.« less

Sedentary behavior and prostate cancer risk in the NIH-AARP Diet and Health Study

PubMed Central

Lynch, Brigid M.; Friedenreich, Christine M.; Kopciuk, Karen A.; Hollenbeck, Albert R.; Moore, Steven C.; Matthews, Charles E.

2014-01-01

Sedentary behavior (sitting time) has been proposed as an independent risk factor for some cancers; however, its role in the development of prostate cancer has not been determined. We examined the prospective associations of self-reported daily sitting time and daily television/video viewing time with risk of developing or dying from prostate cancer among 170,481 men in the NIH-AARP Diet and Health Study. We estimated hazard ratios and 95% confidence intervals using Cox Proportional Hazards regression. Between 1996 and 2006 there were 13,751 incident (including 1,365 advanced) prostate cancer cases identified; prostate cancer mortality (through 2008) was 669. No strong or significant association with prostate cancer risk was seen in fully adjusted models for either daily sitting or television/video time. There was some suggestion of effect modification by body mass index (interaction for television/video time and body mass index, p = 0.02). For total prostate cancer risk, television/video time was associated with a slightly elevated, but non-significant increased amongst obese men (HR=1.28, 95%CI: 0.98, 1.69); a null association was observed amongst overweight men (HR=1.04, 0.89, 1.22); and, for men with a normal body mass index, television/video time was associated with a non-significant risk decrease (HR=0.82, 95%CI: 0.66, 1.01). Similar patterns were observed for total daily sitting and television/video time in advanced prostate cancer and prostate cancer mortality. Sedentary behavior appears to play a limited role in the development of prostate cancer, however we cannot rule out potential effect modification by body mass index or the impact of measurement error on results. PMID:24526287

Prospective multi-institutional study evaluating the performance of prostate cancer risk calculators.

PubMed

Nam, Robert K; Kattan, Michael W; Chin, Joseph L; Trachtenberg, John; Singal, Rajiv; Rendon, Ricardo; Klotz, Laurence H; Sugar, Linda; Sherman, Christopher; Izawa, Jonathan; Bell, David; Stanimirovic, Aleksandra; Venkateswaran, Vasundara; Diamandis, Eleftherios P; Yu, Changhong; Loblaw, D Andrew; Narod, Steven A

2011-08-01

Prostate cancer risk calculators incorporate many factors to evaluate an individual's risk for prostate cancer. We validated two common North American-based, prostate cancer risk calculators. We conducted a prospective, multi-institutional study of 2,130 patients who underwent a prostate biopsy for prostate cancer detection from five centers. We evaluated the performance of the Sunnybrook nomogram-based prostate cancer risk calculator (SRC) and the Prostate Cancer Prevention Trial (PCPT) -based risk calculator (PRC) to predict the presence of any cancer and high-grade cancer. We examined discrimination, calibration, and decision curve analysis techniques to evaluate the prediction models. Of the 2,130 patients, 867 men (40.7%) were found to have cancer, and 1,263 (59.3%) did not have cancer. Of the patients with cancer, 403 (46.5%) had a Gleason score of 7 or more. The area under the [concentration-time] curve (AUC) for the SRC was 0.67 (95% CI, 0.65 to 0.69); the AUC for the PRC was 0.61 (95% CI, 0.59 to 0.64). The AUC was higher for predicting aggressive disease from the SRC (0.72; 95% CI, 0.70 to 0.75) compared with that from the PRC (0.67; 95% CI, 0.64 to 0.70). Decision curve analyses showed that the SRC performed better than the PRC for risk thresholds of more than 30% for any cancer and more than 15% for aggressive cancer. The SRC performed better than the PRC, but neither one added clinical benefit for risk thresholds of less than 30%. Further research is needed to improve the AUCs of the risk calculators, particularly for higher-grade cancer.

Prostate Stereotactic Ablative Radiation Therapy Using Volumetric Modulated Arc Therapy to Dominant Intraprostatic Lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murray, Louise J.; University of Leeds, Leeds; Lilley, John

2014-06-01

Purpose: To investigate boosting dominant intraprostatic lesions (DILs) in the context of stereotactic ablative radiation therapy (SABR) and to examine the impact on tumor control probability (TCP) and normal tissue complication probability (NTCP). Methods and Materials: Ten prostate datasets were selected. DILs were defined using T2-weighted, dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. Four plans were produced for each dataset: (1) no boost to DILs; (2) boost to DILs, no seminal vesicles in prescription; (3) boost to DILs, proximal seminal vesicles (proxSV) prescribed intermediate dose; and (4) boost to DILs, proxSV prescribed higher dose. The prostate planning target volume (PTV)more » prescription was 42.7 Gy in 7 fractions. DILs were initially prescribed 115% of the PTV{sub Prostate} prescription, and PTV{sub DIL} prescriptions were increased in 5% increments until organ-at-risk constraints were reached. TCP and NTCP calculations used the LQ-Poisson Marsden, and Lyman-Kutcher-Burman models respectively. Results: When treating the prostate alone, the median PTV{sub DIL} prescription was 125% (range: 110%-140%) of the PTV{sub Prostate} prescription. Median PTV{sub DIL} D50% was 55.1 Gy (range: 49.6-62.6 Gy). The same PTV{sub DIL} prescriptions and similar PTV{sub DIL} median doses were possible when including the proxSV within the prescription. TCP depended on prostate α/β ratio and was highest with an α/β ratio = 1.5 Gy, where the additional TCP benefit of DIL boosting was least. Rectal NTCP increased with DIL boosting and was considered unacceptably high in 5 cases, which, when replanned with an emphasis on reducing maximum dose to 0.5 cm{sup 3} of rectum (Dmax{sub 0.5cc}), as well as meeting existing constraints, resulted in considerable rectal NTCP reductions. Conclusions: Boosting DILs in the context of SABR is technically feasible but should be approached with caution. If this therapy is adopted, strict rectal constraints are required including Dmax{sub 0.5cc}. If the α/β ratio of prostate cancer is 1.5 Gy or less, then high TCP and low NTCP can be achieved by prescribing SABR to the whole prostate, without the need for DIL boosting.« less

Effect of androgen deprivation therapy on intraprostatic tumour volume identified on 18F choline PET/CT for prostate dose painting radiotherapy.

PubMed

Chan, Joachim; Carver, Antony; Brunt, John N H; Vinjamuri, Sobhan; Syndikus, Isabel

2017-03-01

Prostate dose painting radiotherapy requires the accurate identification of dominant intraprostatic lesions (DILs) to be used as boost volumes; these can be identified on multiparametric MRI (mpMRI) or choline positron emission tomography (PET)/CT. Planning scans are usually performed after 2-3 months of androgen deprivation therapy (ADT). We examine the effect of ADT on choline tracer uptake and boost volumes identified on choline PET/CT. Fluoroethylcholine ( 18 F choline) PET/CT was performed for dose painting radiotherapy planning in patients with intermediate- to high-risk prostate cancer. Initially, they were performed at planning. Owing to low visual tracer uptake, PET/CT for subsequent patients was performed at staging. We compared these two approaches on intraprostatic lesions obtained on PET using both visual and automatic threshold methods [prostate maximum standardized uptake value (SUV max ) 60%] when compared with mpMRI. PET/CT was performed during ADT in 11 patients (median duration of 85 days) and before ADT in 29 patients. ADT significantly reduced overall prostate volume by 17%. During ADT, prostate SUV max was lower although it did not reach statistical significance (4.2 vs 6.6, p = 0.06); three patients had no visually identifiable PET DIL; and visually defined PET DILs were significantly smaller than corresponding mpMRI DILs (p = 0.03). However, all patients scanned before ADT had at least one visually identifiable PET DIL, with no significant size difference between MRI and visually defined PET DILs. In both groups, threshold PET produced larger DILs than visual PET. Both PET methods have moderate sensitivity (0.50-0.68) and high specificity (0.85-0.98) for identifying MRI-defined disease. For visual contouring of boost volumes in prostate dose painting radiotherapy, 18 F choline PET/CT should be performed before ADT. For threshold contouring of boost volumes using our PET/CT scanning protocol, threshold levels of above 60% prostate SUV max may be more suitable. Additional use of PET with MRI for radiotherapy planning can significantly change the overall boost volumes compared with using MRI alone. Advances in knowledge: For prostate dose painting radiotherapy, the additional use of 18 F choline PET with MRI can significantly change the overall boost volumes, and PET should be performed before hormone therapy, especially if boost volumes are visually identified.

Prostate Cancer Screening

MedlinePlus

... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... or routine screening test for prostate cancer. Screening tests for prostate cancer are under study, and there are screening clinical trials taking place ...

Impact of Primary Gleason Grade on Risk Stratification for Gleason Score 7 Prostate Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koontz, Bridget F., E-mail: bridget.koontz@duke.edu; Tsivian, Matvey; Mouraviev, Vladimir

Purpose: To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. Methods: One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Results: Nine hundred seventy-nine patientsmore » had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Conclusions: Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities.« less

Impact of primary Gleason grade on risk stratification for Gleason score 7 prostate cancers.

PubMed

Koontz, Bridget F; Tsivian, Matvey; Mouraviev, Vladimir; Sun, Leon; Vujaskovic, Zeljko; Moul, Judd; Lee, W Robert

2012-01-01

To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Nine hundred seventy-nine patients had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities. Copyright © 2012 Elsevier Inc. All rights reserved.

A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.

PubMed

Al Olama, Ali Amin; Kote-Jarai, Zsofia; Berndt, Sonja I; Conti, David V; Schumacher, Fredrick; Han, Ying; Benlloch, Sara; Hazelett, Dennis J; Wang, Zhaoming; Saunders, Ed; Leongamornlert, Daniel; Lindstrom, Sara; Jugurnauth-Little, Sara; Dadaev, Tokhir; Tymrakiewicz, Malgorzata; Stram, Daniel O; Rand, Kristin; Wan, Peggy; Stram, Alex; Sheng, Xin; Pooler, Loreall C; Park, Karen; Xia, Lucy; Tyrer, Jonathan; Kolonel, Laurence N; Le Marchand, Loic; Hoover, Robert N; Machiela, Mitchell J; Yeager, Merideth; Burdette, Laurie; Chung, Charles C; Hutchinson, Amy; Yu, Kai; Goh, Chee; Ahmed, Mahbubl; Govindasami, Koveela; Guy, Michelle; Tammela, Teuvo L J; Auvinen, Anssi; Wahlfors, Tiina; Schleutker, Johanna; Visakorpi, Tapio; Leinonen, Katri A; Xu, Jianfeng; Aly, Markus; Donovan, Jenny; Travis, Ruth C; Key, Tim J; Siddiq, Afshan; Canzian, Federico; Khaw, Kay-Tee; Takahashi, Atsushi; Kubo, Michiaki; Pharoah, Paul; Pashayan, Nora; Weischer, Maren; Nordestgaard, Borge G; Nielsen, Sune F; Klarskov, Peter; Røder, Martin Andreas; Iversen, Peter; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; Stanford, Janet L; Kolb, Suzanne; Holt, Sarah; Knudsen, Beatrice; Coll, Antonio Hurtado; Gapstur, Susan M; Diver, W Ryan; Stevens, Victoria L; Maier, Christiane; Luedeke, Manuel; Herkommer, Kathleen; Rinckleb, Antje E; Strom, Sara S; Pettaway, Curtis; Yeboah, Edward D; Tettey, Yao; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P; Cannon-Albright, Lisa; Cybulski, Cezary; Wokołorczyk, Dominika; Kluźniak, Wojciech; Park, Jong; Sellers, Thomas; Lin, Hui-Yi; Isaacs, William B; Partin, Alan W; Brenner, Hermann; Dieffenbach, Aida Karina; Stegmaier, Christa; Chen, Constance; Giovannucci, Edward L; Ma, Jing; Stampfer, Meir; Penney, Kathryn L; Mucci, Lorelei; John, Esther M; Ingles, Sue A; Kittles, Rick A; Murphy, Adam B; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej M; Blot, William; Signorello, Lisa B; Zheng, Wei; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Nemesure, Barbara; Carpten, John; Leske, Cristina; Wu, Suh-Yuh; Hennis, Anselm; Kibel, Adam S; Rybicki, Benjamin A; Neslund-Dudas, Christine; Hsing, Ann W; Chu, Lisa; Goodman, Phyllis J; Klein, Eric A; Zheng, S Lilly; Batra, Jyotsna; Clements, Judith; Spurdle, Amanda; Teixeira, Manuel R; Paulo, Paula; Maia, Sofia; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Witte, John S; Casey, Graham; Gillanders, Elizabeth M; Seminara, Daniella; Riboli, Elio; Hamdy, Freddie C; Coetzee, Gerhard A; Li, Qiyuan; Freedman, Matthew L; Hunter, David J; Muir, Kenneth; Gronberg, Henrik; Neal, David E; Southey, Melissa; Giles, Graham G; Severi, Gianluca; Cook, Michael B; Nakagawa, Hidewaki; Wiklund, Fredrik; Kraft, Peter; Chanock, Stephen J; Henderson, Brian E; Easton, Douglas F; Eeles, Rosalind A; Haiman, Christopher A

2014-10-01

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

Fried food and prostate cancer risk: systematic review and meta-analysis.

PubMed

Lippi, Giuseppe; Mattiuzzi, Camilla

2015-01-01

We performed systematic review and meta-analysis of published studies that investigated the potential association between fried food consumption and prostate cancer risk. Four case-control studies were finally selected for this systematic literature review, totaling 2579 cancer patients and 2277 matched controls. In two of these studies, the larger intake of fried food was associated with a 1.3- to 2.3-fold increased risk of prostate cancer, no significant association was found in another, whereas an inverse relationship was observed in the remaining. The meta-analysis of published data showed that larger intake of fried food was associated with a 35% (95% CI 17-57%) increased risk of prostate cancer. The results of this systematic literature review support the notion that larger intake of fried foods may have a role in increasing the risk of prostate cancer.

Investigating the possible causal role of coffee consumption with prostate cancer risk and progression using Mendelian randomization analysis

PubMed Central

Martin, Richard M.; Geybels, Milan S.; Stanford, Janet L.; Shui, Irene; Eeles, Rosalind; Easton, Doug; Kote‐Jarai, Zsofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C; Neal, David; Pashayan, Nora; Khaw, Kay‐Tee; Blot, William; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon‐Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Donovan, Jenny; Munafò, Marcus R.

2016-01-01

Coffee consumption has been shown in some studies to be associated with lower risk of prostate cancer. However, it is unclear if this association is causal or due to confounding or reverse causality. We conducted a Mendelian randomisation analysis to investigate the causal effects of coffee consumption on prostate cancer risk and progression. We used two genetic variants robustly associated with caffeine intake (rs4410790 and rs2472297) as proxies for coffee consumption in a sample of 46,687 men of European ancestry from 25 studies in the PRACTICAL consortium. Associations between genetic variants and prostate cancer case status, stage and grade were assessed by logistic regression and with all‐cause and prostate cancer‐specific mortality using Cox proportional hazards regression. There was no clear evidence that a genetic risk score combining rs4410790 and rs2472297 was associated with prostate cancer risk (OR per additional coffee increasing allele: 1.01, 95% CI: 0.98,1.03) or having high‐grade compared to low‐grade disease (OR: 1.01, 95% CI: 0.97,1.04). There was some evidence that the genetic risk score was associated with higher odds of having nonlocalised compared to localised stage disease (OR: 1.03, 95% CI: 1.01, 1.06). Amongst men with prostate cancer, there was no clear association between the genetic risk score and all‐cause mortality (HR: 1.00, 95% CI: 0.97,1.04) or prostate cancer‐specific mortality (HR: 1.03, 95% CI: 0.98,1.08). These results, which should have less bias from confounding than observational estimates, are not consistent with a substantial effect of coffee consumption on reducing prostate cancer incidence or progression. PMID:27741566

Merging digital rectal exam, family history, age and prostate-specific antigen to create a decision-making tool.

PubMed

Ankerst, Donna Pauler; Thompson, Ian M

2006-12-01

In this paper, we report on risk factors for prostate cancer detection on biopsy as found in the Prostate Cancer Prevention Trial (PCPT), with special emphasis on the independent contribution of prostate-specific antigen (PSA) velocity to prostate cancer risk over that provided by PSA. For this study, we used a subset of PCPT placebo arm participants who had had at least one prostate biopsy and a digital rectal examination (DRE) and PSA measured within 1 year prior to biopsy. In order to evaluate PSA velocity, we also required an additional PSA measurement within 3 years prior to biopsy, yielding 5,519 PCPT placebo arm participants for inclusion in the analysis. The risk of prostate cancer rose from 11.1% for PSA values less than 1 ng/mL to 43.3% for PSA values greater than 6 ng/mL and the risk of high-grade disease rose from 1.0% to 22.0% across these two PSA intervals. It was in fact no longer statistically significant as soon as the single predictor PSA was added to the risk equation, whereas PSA remained statistically significant even when velocity was in the risk equation. Furthermore, in a head-to-head comparison of predictive strength as a single predictor in a model, assessed by maximized log likelihood, PSA was more predictive than PSA velocity. These findings occurred for every definition of velocity that was considered and hence we concluded that velocity did not add independent prognostic information to prostate cancer risk over that provided by PSA. Similarly, age, which is also a predictor of prostate cancer in the absence of other factors, did not add independent prognostic information to PSA, DRE, family history, and prior biopsy.

Impact of a robotic surgical system on treatment choice for men with clinically organ-confined prostate cancer.

PubMed

Kobayashi, Takashi; Kanao, Kent; Araki, Motoo; Terada, Naoki; Kobayashi, Yasuyuki; Sawada, Atsuro; Inoue, Takahiro; Ebara, Shin; Watanabe, Toyohiko; Kamba, Tomomi; Sumitomo, Makoto; Nasu, Yasutomo; Ogawa, Osamu

2018-04-01

Introducing a new surgical technology may affect behaviors and attitudes of patients and surgeons about clinical practice. Robot-assisted laparoscopic radical prostatectomy (RALP) was approved in 2012 in Japan. We investigated whether the introduction of this system affected the treatment of organ-confined prostate cancer (PCa) and the use of radical prostatectomy (RP). We conducted a retrospective multicenter study on 718 patients with clinically determined organ-confined PCa treated at one of three Japanese academic institutions in 2011 (n = 338) or 2013 (n = 380). Two patient groups formed according to the treatment year were compared regarding the clinical characteristics of PCa, whether referred or screened at our hospital, comorbidities and surgical risk, and choice of primary treatment. Distribution of PCa risk was not changed by the introduction of RALP. Use of RP increased by 70% (from 127 to 221 cases, p < 0.0001), whereas the number of those undergoing radiotherapy or androgen deprivation therapy decreased irrespective of the disease risk of PCa. Increased use of RP (from 34 to 100 cases) for intermediate- or high-risk PCa patients with mild perioperative risk (American Society of Anesthesiologists score 2) accounted for 70% of the total RP increase, whereas the number of low- or very low-risk PCa patients with high comorbidity scores (Charlson Index ≥ 4) increased from 8 to 25 cases, accounting for 18%. Use of expectant management (active surveillance, watchful waiting) in very low-risk PCa patients was 15% in 2011 and 12% in 2013 (p = 0.791). Introduction of a robotic surgical system had little effect on the risk distribution of PCa. Use of RP increased, apparently due to increased indications in patients who are candidates for RP but have mild perioperative risk. Although small, there was an increase in the number of RPs performed on patients with severe comorbidities but with low-risk or very low-risk PCa.

Levels of beta-microseminoprotein in blood and risk of prostate cancer in multiple populations.

PubMed

Haiman, Christopher A; Stram, Daniel O; Vickers, Andrew J; Wilkens, Lynne R; Braun, Katharina; Valtonen-André, Camilla; Peltola, Mari; Pettersson, Kim; Waters, Kevin M; Marchand, Loic Le; Kolonel, Laurence N; Henderson, Brian E; Lilja, Hans

2013-02-06

A common genetic variant (rs10993994) in the 5' region of the gene encoding β-microseminoprotein (MSP) is associated with circulating levels of MSP and prostate cancer risk. Whether MSP levels are predictive of prostate cancer risk has not been evaluated. We investigated the prospective relationship between circulating plasma levels of MSP and prostate cancer risk in a nested case-control study of 1503 case subjects and 1503 control subjects among black, Latino, Japanese, Native Hawaiian, and white men from the Multiethnic Cohort study. We also examined the ability of MSP to serve as a biomarker for discriminating prostate cancer case subjects from control subjects. All statistical tests are two-sided. In all racial and ethnic groups, men with lower MSP levels were at greater risk of developing prostate cancer (odds ratio = 1.02 per one unit decrease in MSP, P < .001 in the prostate-specific antigen [PSA]-adjusted analysis). Compared with men in the highest decile of MSP, the multivariable PSA-adjusted odds ratio was 3.64 (95% confidence interval = 2.41 to 5.49) for men in the lowest decile. The positive association with lower MSP levels was observed consistently across racial and ethnic populations, by disease stage and Gleason score, for men with both high and low levels of PSA and across all genotype classes of rs10993994. However, we did not detect strong evidence of MSP levels in improving prostate cancer prediction beyond that of PSA. Regardless of race and ethnicity or rs10993994 genotype, men with low blood levels of MSP have increased risk of prostate cancer.

HIFU therapy for patients with high risk prostate cancer

NASA Astrophysics Data System (ADS)

Solovov, V. A.; Vozdvizhenskiy, M. O.; Matysh, Y. S.

2017-03-01

Objectives. Patients with high-risk prostate cancer undergoing radical prostatectomy, external beam radiation therapy (EBRT) combined with androgen deprivation therapy (ADT) or ADT alone. The widely accepted definition of high-risk prostate was first proposed by D'Amico based on a pretreatment Gleason score of ≥8, clinical stage T3, PSA level ≥20 ng/mL. There is no trial that compares traditional methods of treatment of such patients with HIFU therapy. Here we explored the effectiveness of the HIFU in multimodal treatment for patients with high risk prostate cancer. Materials & Methods. 701 patients with high risk prostate cancer were treated in our center between September 2007 and December 2013. Gleason score were 8-10, stage T3N0M0, age 69 (58-86) years, mean PSA before treatment 43.3 (22.1-92.9) ng/ml, mean prostate volume - 59.3 (38-123) cc. 248 patients were treated by HIFU. We compare this group of patients with patients who undertook EBRT: number 196, and ADT: number 257. Mean follow-up time 58 months (6-72). Results. The 5-year overall survival rates in patients after HIFU were 73.8 %, after EBRT - 63.0 % and after ADT - 18.1%. Conclusions. Our experience showed that HIFU therapy in combined treatment were successful for high risk prostate cancer.

Prostate Cancer Prevention (PDQ®)—Health Professional Version

Cancer.gov

Prostate cancer prevention strategies include avoiding risk factors, increasing protective factors, and considering chemoprevention when appropriate. Get detailed information about factors that influence the risk of prostate cancer and research aimed at preventing it in this clinician summary.

Hypofractionated Radiation Therapy in Treating Participants With Prostate Cancer High-Risk Features Following Radical Prostatectomy

ClinicalTrials.gov

2018-06-25

Prostate Adenocarcinoma; PSA Level Less Than Two; Stage IIB Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8

Overcoming difficulties with equipoise to enable recruitment to a randomised controlled trial of partial ablation versus radical prostatectomy for unilateral localised prostate cancer.

PubMed

Elliott, Daisy; Hamdy, Freddie C; Leslie, Tom A; Rosario, Derek; Dudderidge, Tim; Hindley, Richard; Emberton, Mark; Brewster, Simon; Sooriakumaran, Prasanna; Catto, James W F; Emara, Amr; Ahmed, Hashim; Whybrow, Paul; le Conte, Steffi; Donovan, Jenny L

2018-06-11

To describe how clinicians conceptualised equipoise in the PART (Partial prostate Ablation versus Radical prosTatectomy in intermediate risk, unilateral clinically localised prostate cancer) feasibility study and how this affected recruitment. PART included a QuinteT Recruitment Intervention (QRI) to optimise recruitment. Phase I aimed to understand recruitment, and included scrutinising recruitment data, interviewing the Trial Management Group and recruiters (n=13), and audio-recording recruitment consultations (n=64). Data were analysed using qualitative content and thematic analysis methods. In Phase II, strategies to improve recruitment were developed and delivered. Initially many recruiters found it difficult to maintain a position of equipoise and held preconceptions about which treatment was best for particular patients. They did not feel comfortable about approaching all eligible patients, and when the study was discussed, biases were conveyed through the use of terminology, poorly balanced information and direct treatment recommendations. Individual and group feedback led to presentations to patients becoming clearer and enabled recruiters to reconsider their sense of equipoise. Although the precise impact of the QRI alone cannot be determined, recruitment increased (from mean 1.4 (range=0-4) to 4.5 (range=0-12) patients per month) and the feasibility study reached its recruitment target. Although clinicians find it challenging to recruit participants to a trial comparing different contemporary treatments for prostate cancer, training and support can enable recruiters to become more comfortable with conveying equipoise and providing clearer information to patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Association of Reported Prostate Cancer Risk Alleles With PSA Levels Among Men Without a Diagnosis of Prostate Cancer

PubMed Central

Wiklund, Fredrik; Zheng, S. Lilly; Sun, Jielin; Adami, Hans-Olov; Lilja, Hans; Hsu, Fang-Chi; Stattin, Pär; Adolfsson, Jan; Cramer, Scott D.; Duggan, David; Carpten, John D.; Chang, Bao-Li; Isaacs, William B.; Grönberg, Henrik; Xu, Jianfeng

2012-01-01

BACKGROUND Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels. METHODS We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer. RESULTS Of the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P≤0.05) were found for six SNPs. These six SNPs had a cumulative effect on PSA levels; the mean PSA levels in men were almost twofold increased across increasing quintile of number of PSA associated alleles, P-trend=3.4×10−14. In this Swedish study population risk allele frequencies were similar among T1c case patients (cancer detected by elevated PSA levels alone) as compared to T2 and above prostate cancer case patients. CONCLUSIONS Results from this study may have two important clinical implications. The cumulative effect of six SNPs on PSA levels suggests genetic-specific PSA cutoff values may be used to improve the discriminatory performance of this test for prostate cancer; and the dual associations of these SNPs with PSA levels and prostate cancer risk raise a concern that some of reported prostate cancer risk-associated SNPs may be confounded by the prevalent use of PSA screening. PMID:19116992

Association of prostate cancer risk variants with clinicopathologic characteristics of the disease

PubMed Central

Xu, Jianfeng; Isaacs, Sarah D.; Sun, Jielin; Li, Ge; Wiley, Kathleen E.; Zhu, Yi; Hsu, Fang-Chi; Wiklund, Fredrik; Turner, Aubrey R.; Adams, Tamara S.; Liu, Wennuan; Trock, Bruce J.; Partin, Alan W.; Chang, Baoli; Walsh, Patrick C.; Grönberg, Henrik; Isaacs, William; Zheng, Siqun

2009-01-01

Purpose Fifteen independent genetic variants have been implicated in prostate cancer risk by recent genome-wide association studies. However, their association with clinicopathologic features of prostate cancer is uncertain. Experimental Design We systematically evaluated these 15 variants in 1,563 prostate cancer patients undergoing radical prostatectomy, taking advantage of the uniform tumor stage and grade information available for each of these cases. Associations of these variants with aggressiveness, pathologic Gleason scores, pathologic stage, age at diagnosis, or serum PSA levels were tested. Results After adjusting for multiple testing, none of the SNPs was individually or cumulatively associated with aggressiveness or individual clinicopathologic variables of prostate cancer such as Gleason scores, pathologic stage, or age at diagnosis of prostate cancer. The reported risk allele (G) for SNP rs2735839 in the KLK3 gene at 19q13 was more frequent in less aggressive prostate cancer patients (0.89) than in more aggressive prostate cancer patients (0.86), nominal P = 0.03, or in controls (0.86), nominal P = 0.04. Considering that this allele was also significantly associated with higher serum PSA levels among controls (nominal P = 0.003), the observed trend of higher frequency of this risk allele between less and more aggressive prostate cancer, or between less aggressive and controls may be due to detection bias of PSA screening. Conclusions Prostate cancer risk variants recently discovered from genome-wide case-control association studies are not associated with clinicopathologic variables in this population. Case-case studies are urgently needed in order to discover genetic variants that predict tumor aggressiveness. PMID:18794092

Does Prostate Size Predict the Development of Incident Lower Urinary Tract Symptoms in Men with Mild to No Current Symptoms? Results from the REDUCE Trial.

PubMed

Simon, Ross M; Howard, Lauren E; Moreira, Daniel M; Roehrborn, Claus; Vidal, Adriana C; Castro-Santamaria, Ramiro; Freedland, Stephen J

2016-05-01

It has been shown that increased prostate size is a risk factor for lower urinary tract symptom (LUTS) progression in men who currently have LUTS presumed due to benign prostatic hyperplasia (BPH). To determine if prostate size is a risk factor for incident LUTS in men with mild to no symptoms. We conducted a post hoc analysis of the REDUCE study, which contained a substantial number of men (n=3090) with mild to no LUTS (International Prostate Symptom Score [IPSS] <8). Our primary outcome was determination of the effect of prostate size on incident LUTS presumed due to BPH defined as two consecutive IPSS values >14, or receiving any medical (α-blockers) or surgical treatment for BPH throughout the study course. To determine the risk of developing incident LUTS, we used univariable and multivariable Cox models, as well as Kaplan-Meier curves and the log-rank test. Among men treated with placebo during the REDUCE study, those with a prostate size of 40.1-80ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23-2.26, p=0.001) of developing incident LUTS compared to men with a prostate size 40.0ml or smaller. There was no association between prostate size and risk of incident LUTS in men treated with 0.5mg of dutasteride. The post hoc nature of our study design is a potential limitation. Men with mild to no LUTS but increased prostate size are at higher risk of incident LUTS presumed due to BPH. This association was negated by dutasteride treatment. Benign prostatic hyperplasia (BPH) is a very common problem among older men, which often manifests as lower urinary tract symptoms (LUTS), and can lead to potentially serious side effects. In our study we determined that men with mild to no current LUTS but increased prostate size are much more likely to develop LUTS presumed due to BPH in the future. This association was not seen in men treated with dutasteride, a drug approved for treatment of BPH. Our study reveals that men with a prostate size of 40.1-80ml are potential candidates for closer follow-up. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

A Contemporary Prostate Biopsy Risk Calculator Based on Multiple Heterogeneous Cohorts.

PubMed

Ankerst, Donna P; Straubinger, Johanna; Selig, Katharina; Guerrios, Lourdes; De Hoedt, Amanda; Hernandez, Javier; Liss, Michael A; Leach, Robin J; Freedland, Stephen J; Kattan, Michael W; Nam, Robert; Haese, Alexander; Montorsi, Francesco; Boorjian, Stephen A; Cooperberg, Matthew R; Poyet, Cedric; Vertosick, Emily; Vickers, Andrew J

2018-05-16

Prostate cancer prediction tools provide quantitative guidance for doctor-patient decision-making regarding biopsy. The widely used online Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) utilized data from the 1990s based on six-core biopsies and outdated grading systems. We prospectively gathered data from men undergoing prostate biopsy in multiple diverse North American and European institutions participating in the Prostate Biopsy Collaborative Group (PBCG) in order to build a state-of-the-art risk prediction tool. We obtained data from 15 611 men undergoing 16 369 prostate biopsies during 2006-2017 at eight North American institutions for model-building and three European institutions for validation. We used multinomial logistic regression to estimate the risks of high-grade prostate cancer (Gleason score ≥7) on biopsy based on clinical characteristics, including age, prostate-specific antigen, digital rectal exam, African ancestry, first-degree family history, and prior negative biopsy. We compared the PBCG model to the PCPTRC using internal cross-validation and external validation on the European cohorts. Cross-validation on the North American cohorts (5992 biopsies) yielded the PBCG model area under the receiver operating characteristic curve (AUC) as 75.5% (95% confidence interval: 74.2-76.8), a small improvement over the AUC of 72.3% (70.9-73.7) for the PCPTRC (p<0.0001). However, calibration and clinical net benefit were far superior for the PBCG model. Using a risk threshold of 10%, clinical use of the PBCG model would lead to the equivalent of 25 fewer biopsies per 1000 patients without missing any high-grade cancers. Results were similar on external validation on 10 377 European biopsies. The PBCG model should be used in place of the PCPTRC for prediction of prostate biopsy outcome. A contemporary risk tool for outcomes on prostate biopsy based on the routine clinical risk factors is now available for informed decision-making. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Interest in genomic SNP testing for prostate cancer risk: a pilot survey.

PubMed

Hall, Michael J; Ruth, Karen J; Chen, David Yt; Gross, Laura M; Giri, Veda N

2015-01-01

Advancements in genomic testing have led to the identification of single nucleotide polymorphisms (SNPs) associated with prostate cancer. The clinical utility of SNP tests to evaluate prostate cancer risk is unclear. Studies have not examined predictors of interest in novel genomic SNP tests for prostate cancer risk in a diverse population. Consecutive participants in the Fox Chase Prostate Cancer Risk Assessment Program (PRAP) (n = 40) and unselected men from surgical urology clinics (n = 40) completed a one-time survey. Items examined interest in genomic SNP testing for prostate cancer risk, knowledge, impact of unsolicited findings, and psychosocial factors including health literacy. Knowledge of genomic SNP tests was low in both groups, but interest was higher among PRAP men (p < 0.001). The prospect of receiving unsolicited results about ancestral genomic markers increased interest in testing in both groups. Multivariable modeling identified several predictors of higher interest in a genomic SNP test including higher perceived risk (p = 0.025), indicating zero reasons for not wanting testing (vs ≥1 reason) (p = 0.013), and higher health literacy (p = 0.016). Knowledge of genomic SNP testing was low in this sample, but higher among high-risk men. High-risk status may increase interest in novel genomic tests, while low literacy may lessen interest.

DNA Ploidy Measured on Archived Pretreatment Biopsy Material May Correlate With Prostate-Specific Antigen Recurrence After Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keyes, Mira, E-mail: mkeyes@bccancer.bc.ca; MacAulay, Calum; Hayes, Malcolm

Purpose: To explore whether DNA ploidy of prostate cancer cells determined from archived transrectal ultrasound-guided biopsy specimens correlates with disease-free survival. Methods and Materials: Forty-seven failures and 47 controls were selected from 1006 consecutive low- and intermediate-risk patients treated with prostate {sup 125}I brachytherapy (July 1998-October 2003). Median follow-up was 7.5 years. Ten-year actuarial disease-free survival was 94.1%. Controls were matched using age, initial prostate-specific antigen level, clinical stage, Gleason score, use of hormone therapy, and follow-up (all P nonsignificant). Seventy-eight specimens were successfully processed; 27 control and 20 failure specimens contained more than 100 tumor cells were used formore » the final analysis. The Feulgen-Thionin stained cytology samples from archived paraffin blocks were used to determine the DNA ploidy of each tumor by measuring integrated optical densities. Results: The samples were divided into diploid and aneuploid tumors. Aneuploid tumors were found in 16 of 20 of the failures (80%) and 8 of 27 controls (30%). Diploid DNA patients had a significantly lower rate of disease recurrence (P=.0086) (hazard ratio [HR] 0.256). On multivariable analysis, patients with aneuploid tumors had a higher prostate-specific antigen failure rate (HR 5.13). Additionally, those with “excellent” dosimetry (V100 >90%; D90 >144 Gy) had a significantly lower recurrence rate (HR 0.25). All patients with aneuploid tumors and dosimetry classified as “nonexcellent” (V100 <90%; D90 <144 Gy) (5 of 5) had disease recurrence, compared with 40% of patients with aneuploid tumors and “excellent” dosimetry (8 of 15). In contrast, dosimetry did not affect the outcome for diploid patients. Conclusions: Using core biopsy material from archived paraffin blocks, DNA ploidy correctly classified the majority of failures and nonfailures in this study. The results suggest that DNA ploidy can be used as a useful marker for aggressiveness of localized prostate cancer. A larger study will be necessary to further confirm our hypothesis.« less

The Association between Statin Use and the Diagnosis of Prostate Cancer in a Population-Based Cohort

PubMed Central

Breau, Rodney H.; Karnes, R. Jeffrey; Jacobson, Debra J.; McGree, Michaela E.; Jacobsen, Steven J.; Nehra, Ajay; Lieber, Michael M.; St. Sauver, Jennifer L.

2011-01-01

Purpose The effect of statin medication use on risk of prostate cancer is unknown. Materials and Methods We examined data from a longitudinal, population-based cohort of 2447 men between the ages of 40 and 79 that were followed from 1990 to 2007. Information on statin use was self-reported and obtained by biennial questionnaires. A randomly selected subset of men (634; 26%) completed biennial urologic examinations that included serum PSA measurements. Information on prostate biopsy and prostate cancer was obtained through review of community medical records. Results Of 634 statin users, 38 (6%) were diagnosed with prostate cancer compared to 186 (10%) of 1813 non-statin users. Statin use was associated with a decreased risk of receiving a prostate biopsy (HR: 0.31; 95% CI: 0.24, 0.40), prostate cancer diagnosis (HR: 0.36; 95% CI: 0.25, 0.53) and high-grade (Gleason ≥7) prostate cancer diagnosis (HR: 0.25; 95% CI: 0.11, 0.58). Statin use was also associated with a non-significant decreased risk of exceeding a PSA threshold of 4.0 ng/mL (HR: 0.63; 95% CI: 0.35, 1.13). In addition, longer duration of statin use was associated with lower risk of these outcomes (all tests for trend p<0.05). Conclusions Statin use is associated with a decreased risk of prostate cancer diagnosis. This association may be explained by decreased detection or cancer prevention. PMID:20620405

Insufficient Sleep and Risk of Prostate Cancer in a Large Swedish Cohort.

PubMed

Markt, Sarah C; Grotta, Alessandra; Nyren, Olof; Adami, Hans-Olov; Mucci, Lorelei A; Valdimarsdottir, Unnur A; Stattin, Pär; Bellocco, Rino; Lagerros, Ylva Trolle

2015-09-01

There are some data to suggest that insufficient sleep, including short sleep duration and sleep disruption, may be associated with an increased risk of cancer. We investigated the association between sleep duration and sleep disruption and risk of prostate cancer. Prospective cohort study. Sweden. A total of 14,041 men in the Swedish National March Cohort. None. Habitual sleep duration and sleep disruption were self-reported in 1997. Prostate cancer diagnoses, including lethal (metastases at diagnosis or death from prostate cancer) and advanced (stage T4, N1, or M1 at diagnosis or death from prostate cancer), were determined from linkage to nationwide cancer registries through 2010. We conducted Cox proportional hazards regression adjusted for potential confounding variables. During 13 years of follow-up, we identified 785 cases of incident prostate cancer, including 118 lethal and 127 advanced cases. Four percent of men reported sleeping 5 h or less a night, and 2% reported sleeping 9 h or more per night. We found no association between sleep duration and risk of prostate cancer overall or for advanced/lethal disease. We also did not find an association between prostate cancer and sleep disruption, as defined by difficulty falling asleep, difficulty maintaining sleep, sleep quality, and restorative power of sleep. In this large prospective study from Sweden, we found no association between habitual sleep duration or sleep disruption and risk of prostate cancer. © 2015 Associated Professional Sleep Societies, LLC.

Potential role of gastrointestinal microbiota composition in prostate cancer risk

PubMed Central

2013-01-01

Background Among men in the U.S., prostate cancer is the most common cancer and the second leading cause of cancer death. Despite its prevalence, there are few established risk factors for prostate cancer. Some studies have found that intake of certain foods/nutrients may be associated with prostate cancer risk, but few have accounted for how intake and metabolic factors may interact to influence bioavailable nutrient levels and subsequent disease risk. Presentation of the hypothesis The composition of the gastrointestinal (GI) microbiome may influence metabolism of dietary compounds and nutrients (e.g., plant phenols, calcium, choline) that may be relevant to prostate cancer risk. We, therefore, propose the hypothesis that GI microbiota may have a markedly different composition among individuals with higher prostate cancer risk. These individuals could have microbial profiles that are conducive to intestinal inflammation and/or are less favorable for the metabolism and uptake of chemopreventive agents. Testing the hypothesis Because very little preliminary data exist on this potential association, a case–control study may provide valuable information on this topic. Such a study could evaluate whether the GI microbial profile is markedly different between three groups of individuals: healthy men, those with latent prostate cancer, and those with invasive prostate cancer. Any findings could then be validated in a larger study, designed to collect a series of specimens over time. Implications of the hypothesis Given the plethora of information emerging from the Human Microbiome Project, this is an opportune time to explore associations between the microbiome and complex human diseases. Identification of profiles that alter the host’s risk for disease may clarify inconsistencies in the literature on dietary factors and cancer risk, and could provide valuable targets for novel cancer prevention strategies. PMID:24180596

Genetic polymorphisms of xeroderma pigmentosum group D gene Asp312Asn and Lys751Gln and susceptibility to prostate cancer: a systematic review and meta-analysis.

PubMed

Ma, Qingtong; Qi, Can; Tie, Chong; Guo, Zhanjun

2013-11-10

Many studies have reported the role of xeroderma pigmentosum group D (XPD) with prostate cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. A total of 8 studies including 2620 cases and 3225 controls described Asp312Asn genotypes, among which 10 articles involving 3230 cases and 3582 controls described Lys751Gln genotypes and were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, a significant association between prostate cancer risk and XPD Asp312Asn polymorphism was found. For Asp312Asn polymorphism, in the stratified analysis by ethnicity and source of controls, prostate cancer risk was observed in co-dominant, dominant and recessive models, while no evidence of any associations of XPD Lys751Gln polymorphism with prostate cancer was found in the overall or subgroup analyses. Our meta-analysis supports that the XPD Asp312Asn polymorphism contributed to the risk of prostate cancer from currently available evidence. However, a study with a larger sample size is needed to further evaluate gene-environment interaction on XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. © 2013.

The prevalence of and risk factors for prostatitis-like symptoms and its relation to erectile dysfunction in Chinese men.

PubMed

Zhang, Z; Li, Z; Yu, Q; Wu, C; Lu, Z; Zhu, F; Zhang, H; Liao, M; Li, T; Chen, W; Xian, X; Tan, A; Mo, Z

2015-11-01

The aim of this study was to describe the prevalence of and risk factors for prostatitis-like symptoms and its relation to erectile dysfunction (ED) among southern Chinese men. Data were collected from 2790 men attending the Fangchenggang Area Male Healthy and Examination Survey from September 2009 to December 2009. The prostatitis-like symptoms were assessed by the NIH Chronic Prostatitis Symptom Index and ED was assessed using the 5-item International Index of Erectile Function. Lifestyle and demographic characteristics were obtained through a questionnaire. Prevalence of prostatitis-like symptoms was 12.4% among 2790 Chinese men aged 20-84 years. In smokers who smoked ≥20 cigarettes per day (age-adjusted OR = 1.29; 95% CI = 1.00-1.66; p = 0.04), physical inactivity (age-adjusted OR = 1.31; 95% CI = 1.03-1.66; p = 0.02) was a significant risk factor for prostatitis-like symptoms. Alcohol consumption (daily drinking) also was a risk factor for prostatitis-like symptoms, although the differences were not statistically significant (age-adjusted OR = 1.36; 95% CI = 0.96-1.92; p = 0.07). Those with diabetes may also be at higher risk for prostatitis-like symptoms (age-adjusted OR = 1.37; 95% CI = 0.85-2.21; p = 0.19). In addition, men with ED were more likely to have had prostatitis-like symptoms (age-adjusted OR = 1.86; 95% CI = 0.47-2.36; p < 0.0001), and the ORs increased with increasing severity of ED status (mild ED, mild to moderate ED, and moderate to severe ED were 1.57, 2.62, and 3.24, respectively. Test for trend, p = 0.0001). Our results show that prostatitis-like symptoms are prevalent in Southern China affecting men of all ages. Smoking, drinking, lack of physical activity, and elevated plasma glucose level were associated with an increased risk of prostatitis-like symptoms. In addition, our results reveal that ED accounted for a large proportion (61.5%) among men with prostatitis-like symptoms; we also confirm the magnitude of ED associated with prostatitis-like symptoms. Thus, interventions to evaluate and improve ED might help ameliorate prostatitis-like symptoms and vice versa. © 2015 American Society of Andrology and European Academy of Andrology.

Repeat prostate-specific antigen (PSA) test before prostate biopsy: a 20% decrease in PSA values is associated with a reduced risk of cancer and particularly of high-grade cancer.

PubMed

De Nunzio, Cosimo; Lombardo, Riccardo; Nacchia, Antonio; Tema, Giorgia; Tubaro, Andrea

2018-07-01

To analyse the impact of repeating a prostate-specific antigen (PSA) level assessment on prostate biopsy decision in a cohort of men undergoing prostate biopsy. From 2015 onwards, we consecutively enrolled, at a single institution in Italy, men undergoing 12-core transrectal ultrasonography-guided prostate needle biopsy. Indication for prostate biopsy was a PSA level of ≥4 ng/mL. Demographic, clinical, and histopathological data were collected. The PSA level was tested at enrolment (PSA 1 ) and 4 weeks later on the day before biopsy (PSA 2 ). Variations in PSA level were defined as: stable PSA 2 within a 10% variation, stable PSA 2 within a 20% variation, PSA 2 decreased by ≥10%, PSA 2 decreased by ≥20%, PSA 2 increased by ≥10%, PSA 2 increased by ≥20%, and PSA 2 <4 ng/mL. Percentages and multinomial logistic regression were used to analyse biopsy outcomes. High-grade cancer was defined as Grade group ≥3. Overall, 331 patients were enrolled. Prostate cancer was diagnosed in 153/331 (46%) patients and of them 80/153 (52%) had high-grade disease. When compared to the rest of the population, patients with a stable PSA within 20% variation had a higher risk of prostate cancer (odds ratio [OR] 1.80, P < 0.05) and high grade disease (OR 2.56, P < 0.05), patients with a PSA2 decreased by ≥20% had a lower risk of prostate cancer (OR 0.37, P < 0.05) and high grade disease (OR 0.13, P < 0.05), whilst patients with a PSA2 increased by ≥10% had an increased risk of high-grade prostate cancer (OR 1.93, P < 0.05). When PSA returned to normal values (<4 ng/mL) both risks of prostate cancer and high-grade disease were reduced (OR 0.33 and 0.01, respectively, P = 0.001). In a cohort of Italian men undergoing prostate biopsy, a reduction of ≥20% in PSA levels significantly reduced the risk of high-grade prostate cancer. Further multicentre studies should validate our present results. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Macroscopic Hematuria After Conventional or Hypofractionated Radiation Therapy: Results From a Prospective Phase 3 Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanguineti, Giuseppe, E-mail: sanguineti@ifo.it; Arcidiacono, Fabio; Landoni, Valeria

2016-10-01

Purpose: To assess the macroscopic hematuria rates within a single-institution randomized phase 3 trial comparing dose-escalated, conventionally fractionated radiation therapy (CFRT) and moderately hypofractionated radiation therapy (MHRT) for localized prostate cancer. Methods and Materials: Patients with intermediate- to high-risk localized prostate cancer were treated with conformal RT and short-course androgen deprivation. Both the prostate and the entire seminal vesicles were treated to 80 Gy in 40 fractions over 8 weeks (CFRT) or 62 Gy in 20 fractions over 5 weeks (MHRT). The endpoint of the present study was the development of any episode or grade of macroscopic hematuria. The median follow-up period was 93 monthsmore » (range 6-143). Results: Macroscopic hematuria was reported by 25 of 168 patients (14.9%). The actuarial estimate of hematuria at 8 years was 17.0% (95% confidence interval [CI] 10.7%-23.3%). The number of patients with hematuria was 6 and 19 in the CFRT and MHRT arms, respectively, for an actuarial 8-year estimate of 9.7% and 24.3%, respectively (hazard ratio 3.468, 95% CI 1.385-8.684; P=.008). Overall, 8 of 25 patients were found to have biopsy-proven urothelial carcinoma (3 in the CFRT arm and 5 in the MHRT arm; P=.27). Thus, the 8-year actuarial incidence of macroscopic hematuria (after censoring urothelial cancer–related episodes) was 4.1% and 18.2% after CFRT and MHRT, respectively (hazard ratio 4.961, 95% CI 1.426-17.263; P=.012). The results were confirmed by multivariate analysis after accounting for several patient-, treatment-, and tumor-related covariates. Conclusions: MHRT was associated with a statistically significant increased risk of macroscopic hematuria compared with CFRT.« less

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2011-09-01

placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer. In Year 3 of the...risk. Our study is nested within the Prostate Cancer Prevention Trial (PCPT), a randomized placebo-controlled clinical trial to determine if finasteride

Lifestyle and Risk of Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Cohort of United States Male Health Professionals

PubMed Central

Zhang, Ran; Sutcliffe, Siobhan; Giovannucci, Edward; Willett, Walter C.; Platz, Elizabeth A.; Rosner, Bernard A.; Dimitrakoff, Jordan D.; Wu, Kana

2015-01-01

Purpose Although chronic prostatitis/chronic pelvic pain syndrome is a prevalent urological disorder among men of all ages, its etiology remains unknown. Only a few previous studies have examined associations between lifestyle factors and chronic prostatitis/chronic pelvic pain syndrome, of which most were limited by the cross-sectional study design and lack of control for possible confounders. To address these limitations we performed a cohort study of major lifestyle factors (obesity, smoking and hypertension) and chronic prostatitis/chronic pelvic pain syndrome risk in the HPFS (Health Professionals Follow-up Study), a large ongoing cohort of United States based male health professionals. Materials and Methods The HPFS includes 51,529 men who were 40 to 75 years old at baseline in 1986. At enrollment and every 2 years thereafter participants have completed questionnaires on lifestyle and health conditions. In 2008 participants completed an additional set of questions on recent chronic prostatitis/chronic pelvic pain syndrome pain symptoms modified from the NIH (National Institutes of Health)-CPSI (Chronic Prostatitis Symptom Index) as well as questions on approximate date of symptom onset. The 653 participants with NIH-CPSI pain scores 8 or greater who first experienced symptoms after 1986 were considered incident chronic prostatitis/chronic pelvic pain syndrome cases and the 19,138 who completed chronic prostatitis/chronic pelvic pain syndrome questions but did not report chronic prostatitis/chronic pelvic pain syndrome related pain were considered noncases. Results No associations were observed for baseline body mass index, waist circumference, waist-to-hip ratio, cigarette smoking and hypertension with chronic prostatitis/chronic pelvic pain syndrome risk (each OR ≤1.34). Conclusions In this large cohort study none of the lifestyle factors examined was associated with chronic prostatitis/chronic pelvic pain syndrome risk. As the etiology of chronic prostatitis/chronic pelvic pain syndrome remains unknown, additional prospective studies are needed to elucidate modifiable risk factors for this common condition. PMID:26070893

Associations between fruit, vegetable and legume intakes and prostate cancer risk: results from the prospective Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort.

PubMed

Diallo, Abou; Deschasaux, Mélanie; Galan, Pilar; Hercberg, Serge; Zelek, Laurent; Latino-Martel, Paule; Touvier, Mathilde

2016-05-01

Although experimental studies suggest that fruits, vegetables and legumes may exert protective effects against prostate carcinogenesis through various bioactive compounds such as dietary fibre and antioxidants, epidemiological evidence is lacking. Notably, very few prospective studies have investigated the relationship between legume intake and prostate cancer risk. Our objective was to prospectively investigate the association between fruit, vegetable, tomato products, potatoes and legume intakes and prostate cancer risk. This study included 3313 male participants to the SUpplémentation en VItamines et Minéraux AntioXydants cohort (follow-up: 1994-2007) who completed at least three 24-h dietary records during the first 2 years of follow-up. Associations between tertiles of intake and prostate cancer risk were assessed by multivariate Cox proportional hazards models. After a median follow-up of 12·6 years, 139 incident prostate cancers were diagnosed. An inverse association was observed between prostate cancer risk and tertiles of legume intake (hazard ratio (HR)T3v.T1=0·53; 95 % CI 0·34, 0·85; P trend=0·009). This association was maintained after excluding soya and soya products from the legume group (HRT3 v.T1=0·56; 95 % CI 0·35, 0·89; P trend=0·02). No association was observed between prostate cancer risk and tertiles of intakes of fruits (P trend=0·25), vegetables (P trend=0·91), potatoes (P trend=0·77) and tomato products (P trend=0·09). This prospective study confirms the null association between fruit and non-starchy vegetable intakes and prostate cancer risk observed in most previous cohorts. In contrast, although very few prospective studies have been published on the topic, our results suggest an inverse association between legume intake and prostate cancer risk, supported by mechanistic plausibility. These results should be confirmed by large-scale observational and intervention studies.

Long-term allopurinol use decreases the risk of prostate cancer in patients with gout: a population-based study.

PubMed

Shih, H-J; Kao, M-C; Tsai, P-S; Fan, Y-C; Huang, C-J

2017-09-01

Clinical observations indicated an increased risk of developing prostate cancer in gout patients. Chronic inflammation is postulated to be one crucial mechanism for prostate carcinogenesis. Allopurinol, a widely used antigout agent, possesses potent anti-inflammation capacity. We elucidated whether allopurinol decreases the risk of prostate cancer in gout patients. We analyzed data retrieved from Taiwan National Health Insurance Database between January 2000 and December 2012. Patients diagnosed with gout during the study period with no history of prostate cancer and who had never used allopurinol were selected. Four allopurinol use cohorts (that is, allopurinol use (>365 days), allopurinol use (181-365 days), allopurinol use (91-180 days) and allopurinol use (31-90 days)) and one cohort without using allopurinol (that is, allopurinol use (No)) were included. The study end point was the diagnosis of new-onset prostate cancer. Multivariable Cox proportional hazards regression and propensity score-adjusted Cox regression models were used to estimate the association between the risk of prostate cancer and allopurinol treatment in gout patients after adjusting for potential confounders. A total of 25 770 gout patients (aged between 40 and 100 years) were included. Multivariable Cox regression analyses revealed that the risk of developing prostate cancer in the allopurinol use (>365 days) cohort was significantly lower than the allopurinol use (No) cohort (adjusted hazard ratio (HR)=0.64, 95% confidence interval (CI)=0.45-0.9, P=0.011). After propensity score adjustment, the trend remained the same (adjusted HR=0.66, 95% CI=0.46-0.93, P=0.019). Long-term (more than 1 year) allopurinol use may associate with a decreased risk of prostate cancer in gout patients.

Can the Mediterranean diet prevent prostate cancer?

PubMed

Itsiopoulos, Catherine; Hodge, Allison; Kaimakamis, Mary

2009-02-01

Prostate cancer is the second most common cancer in men worldwide. Despite the global importance of this cancer, until recently little was known about risk factors apart from the well-established factors: age, family history and country of birth. The large worldwide variation in prostate cancer risk and increased risk in migrants moving from low to high risk countries provides strong support for modifiable environmental factors. We have based our review on the findings of a systematic review undertaken by an expert panel on behalf of the World Cancer Research Fund and the American Institute for Cancer Research, and new data since then, linking identified foods and nutrients with prostate cancer. Evidence indicates that foods containing lycopene, as well as selenium and foods containing it, probably protect against prostate cancer, and excess consumption of foods or supplements containing calcium are a probable cause of this cancer. The expert panel also concluded that it is unlikely that beta-carotene (whether from foods or supplements) has a substantial effect on the risk of this cancer. A recent review on environmental factors in human prostate cancer also found that there were protective effects of vitamin E, pulses, soy foods and high plasma 1,25-dihydroxyvitamin D levels. The Mediterranean diet is abundant in foods that may protect against prostate cancer and is associated with longevity and reduced cardiovascular and cancer mortality. Compared with many Western countries Greece has lower prostate cancer mortality and Greek migrant men in Australia have retained their low risk for prostate cancer. Consumption of a traditional Mediterranean diet, rich in bioactive nutrients, may confer protection to Greek migrant men, and this dietary pattern offers a palatable alternative for prevention of this disease.

Prostate Cancer Mortality in Puerto Rican Men: The Effect of Body Habitus and Physical Activity

DTIC Science & Technology

2005-02-01

2001 ;23(1):3-13. 3. Chan, J. M. and Giovannucci, E. L. Vegetables, Fruits, Associated Micronutrients , and Risk of Prostate Cancer. Epidemiol.Rev...2001;23(1):82-6. 4. Chan, J. M. and Giovannucci, E. L. Dairy Products, Calcium, and Vitamin D and Risk of Prostate Cancer. Epidemiol.Rev. 2001 ;23( 1): 87...92. 5. Chan, J. M., Stampfer, M. J., Ma, J., Gann, P. H., Gaziano, J. M., and Giovannucci, E. L. Dairy Products, Calcium, and Prostate Cancer Risk in

Cholesterol and Prostate Cancer

PubMed Central

Pelton, Kristine; Freeman, Michael R.; Solomon, Keith R.

2012-01-01

Summary Prostate cancer risk can be modified by environmental factors, however the molecular mechanisms affecting susceptibility to this disease are not well understood. As a result of a series of recently published studies, the steroidal lipid, cholesterol, has emerged as a clinically relevant therapeutic target in prostate cancer. This review summarizes the findings from human studies as well as animal and cell biology models which suggest that high circulating cholesterol increases risk of aggressive prostate cancer, while cholesterol lowering strategies may confer protective benefit. Relevant molecular processes that have been experimentally tested and might explain these associations are described. We suggest that these promising results now could be applied prospectively to attempt to lower risk of prostate cancer in select populations. PMID:22824430

Prostate cancer family history and eligibility for active surveillance: a systematic review of the literature.

PubMed

Telang, Jaya M; Lane, Brian R; Cher, Michael L; Miller, David C; Dupree, James M

2017-10-01

Active surveillance (AS) is an increasingly prevalent treatment choice for low grade prostate cancer. Eligibility criteria for AS are varied and it is unclear if family history of prostate cancer should be used as an exclusion criterion when considering men for AS. To determine whether family history plays a significant role in the progression of prostate cancer for men undergoing active surveillance, PubMed searches of 'family history and prostate cancer', 'family history and prostate cancer progression' and 'factors of prostate cancer progression' were used to identify research publications about the relationship between family history and prostate cancer progression. These searches generated 536 papers that were screened and reviewed. Six publications were ultimately included in this analysis. Review of the six publications suggests that family history does not increase the risk of prostate cancer progression, whilst a subgroup analysis in one study found that family history increases the risk of prostate cancer progression only in African-Americans. A family history of prostate cancer does not appear to increase a patient's risk of having more aggressive prostate cancer and is therefore unlikely to be an important factor in determining eligibility for AS. Further studies are needed to better understand the relationship between race, family history, and eligibility for AS. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

The relationship between total testosterone levels and prostate cancer: a review of the continuing controversy.

PubMed

Klap, Julia; Schmid, Marianne; Loughlin, Kevin R

2015-02-01

For many years it was believed that higher total testosterone contributed to prostate cancer and caused rapid cancer growth. International guidelines consider that adequate data are not available to determine whether there is additional risk of prostate cancer from testosterone replacement. Numerous studies with multiple designs and contradictory conclusions have investigated the relationship between total testosterone and prostate cancer development. To establish current knowledge in this field we reviewed the literature on total testosterone and the subsequent risk of prostate cancer as well as the safety of exogenous testosterone administration in patients with a history of prostate cancer. We searched the literature to identify articles from 1994 to 2014 related to the relationship between total testosterone and prostate cancer. Emphasis was given to prospective studies, series with observational data and randomized, controlled trials. Case reports were excluded. Articles on testosterone replacement safety were selected by patient population (under active surveillance or with a prostate cancer history). We organized our results according to the relationship between total testosterone and prostate cancer, including 1) the possible link between low total testosterone and prostate cancer, 2) the effect of high levels and 3) the absence of any link. Finally, we summarized studies of the risk of exogenous testosterone administration in patients already diagnosed with prostate cancer, treated or on active surveillance. We selected 45 articles of the relationship between total testosterone and prostate cancer, of which 18 and 17 showed a relationship to low and high total testosterone, respectively, and 10 showed no relation. Total testosterone was defined according to the definition in each article. Contradictory findings have been reported, largely due to the disparate methodologies used in many studies. Most studies did not adhere to professional society guidelines on total testosterone measurements. One of 18 series of low total testosterone and prostate cancer adhered to published guidelines while none of 17 showing a relationship of high total testosterone to prostate cancer and only 1 of 10 that identified no relationship between total testosterone and prostate cancer adhered to measurements recommended in the guidelines. In 11 studies the risk of exogenous testosterone was examined in patients with a prostate cancer history. Many studies were limited by small cohort size and brief followup. However, overall this literature suggests that the risk of exogenous testosterone replacement in patients with prostate cancer appears to be small. The relationship between total testosterone and prostate cancer has been an area of interest among physicians for decades. Conflicting results have been reported on the relationship between total testosterone and subsequent prostate cancer. Much of this controversy appears to be based on conflicting study designs, definitions and methodologies. To date no prospective study with sufficient power has been published to unequivocally resolve the issue. The preponderance of studies of the safety of exogenous testosterone in men with a prostate cancer history suggests that there is little if any risk. However, because the risk has not proved to be zero, the most prudent course is to follow such men with regular prostate specific antigen measurements and digital rectal examinations. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Repeat polymorphisms in estrogen metabolism genes and prostate cancer risk: results from the Prostate Cancer Prevention Trial

PubMed Central

Tang, Li; Yao, Song; Till, Cathee; Goodman, Phyllis J.; Tangen, Catherine M.; Wu, Yue; Kristal, Alan R.; Platz, Elizabeth A.; Neuhouser, Marian L.; Stanczyk, Frank Z.; Reichardt, Juergen K.V.; Santella, Regina M.; Hsing, Ann; Hoque, Ashraful; Lippman, Scott M.; Thompson, Ian M.; Ambrosone, Christine B.

2011-01-01

The etiology of prostate cancer remains elusive, although steroid hormones probably play a role. Considering the carcinogenic potential of estrogen metabolites as well as altered intraprostatic estrogen biosynthesis during the development of prostate cancer, we investigated associations between repeat polymorphisms of three key estrogen-related genes (CYP11A1, CYP19A1, UGT1A1) and risk of prostate cancer in the Prostate Cancer Prevention Trial (PCPT), designed to test finasteride versus placebo as a chemoprevention agent. Using data and specimens from 1154 cases and 1351 controls who were frequency matched on age, family history of prostate cancer and PCPT treatment arm, we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) separately in the placebo and finasteride arms. Among men in the placebo arm, CYP19A1 7/8 genotype carriers had a significantly higher risk of prostate cancer compared with those with the 7/7 genotype (OR = 1.70, 95% CI = 1.16–2.5), regardless of Gleason grade. This genotype was also associated with elevated serum estrogen levels. For the (TA)n repeat polymorphism in UGT1A1, the heterozygous short (<7 repeats)/long (≥7 repeats) genotype was significantly associated with the risk of low-grade prostate cancer (OR = 1.34, 95% CI = 1.05–1.70) compared with the short/short genotype. No significant association was found with CYP11A1. These associations were not observed among men in the finasteride arm. The results indicate that repeat polymorphisms in genes involved in estrogen biosynthesis and metabolism may influence risk of prostate cancer but that their effects may be modified by factors altering hormone metabolism, such as finasteride treatment. PMID:21771722

Fruit and vegetable intake and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

PubMed Central

Travis, Ruth C.; Appleby, Paul N.; Tsilidis, Konstantinos K.; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Katzke, Verena; Kühn, Tilman; Trichopoulou, Antonia; Peppa, Eleni; Kritikou, Maria; Sieri, Sabina; Palli, Domenico; Sacerdote, Carlotta; Tumino, Rosario; Bueno‐de‐Mesquita, H. B(as); Agudo, Antonio; Larrañaga, Nerea; Molina‐Portillo, Elena; Ardanaz, Eva; Chirlaque, Maria‐Dolores; Lasheras, Cristina; Stattin, Pär; Wennberg, Maria; Drake, Isabel; Malm, Johan; Schmidt, Julie A.; Khaw, Kay‐Tee; Gunter, Marc; Freisling, Heinz; Huybrechts, Inge; Aune, Dagfinn; Cross, Amanda J; Riboli, Elio; Key, Timothy J.

2017-01-01

Several dietary factors have been studied in relation to prostate cancer; however, most studies have not reported on subtypes of fruit and vegetables or tumor characteristics, and results obtained so far are inconclusive. This study aimed to examine the prospective association of total and subtypes of fruit and vegetable intake with the incidence of prostate cancer overall, by grade and stage of disease, and prostate cancer death. Lifestyle information for 142,239 men participating in the European Prospective Investigation into Cancer and Nutrition from 8 European countries was collected at baseline. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow‐up time of 13.9 years, 7,036 prostate cancer cases were identified. Compared with the lowest fifth, those in the highest fifth of total fruit intake had a significantly reduced prostate cancer risk (HR = 0.91; 95% CI = 0.83–0.99; p‐trend = 0.01). No associations between fruit subtypes and prostate cancer risk were observed, except for citrus fruits, where a significant trend was found (HR = 0.94; 95% CI = 0.86–1.02; p‐trend = 0.01). No associations between total and subtypes of vegetables and prostate cancer risk were observed. We found no evidence of heterogeneity in these associations by tumor grade and stage, with the exception of significant heterogeneity by tumor grade (p heterogeneity<0.001) for leafy vegetables. No significant associations with prostate cancer death were observed. The main finding of this prospective study was that a higher fruit intake was associated with a small reduction in prostate cancer risk. Whether this association is causal remains unclear. PMID:28419475

Risk assessment models to evaluate the necessity of prostate biopsies in North Chinese patients with 4-50 ng/mL PSA.

PubMed

Zhao, Jing; Liu, Shuai; Gao, Dexuan; Ding, Sentai; Niu, Zhihong; Zhang, Hui; Huang, Zhilong; Qiu, Juhui; Li, Qing; Li, Ning; Xie, Fang; Cui, Jilei; Lu, Jiaju

2017-02-07

Prostate-specific antigen (PSA) is widely used for prostate cancer screening, but low specificity results in high false positive rates of prostate biopsies. To develop new risk assessment models to overcome the diagnostic limitation of PSA and reduce unnecessary prostate biopsies in North Chinese patients with 4-50 ng/mL PSA. A total of 702 patients in seven hospitals with 4-10 and 10-50 ng/mL PSA, respectively, who had undergone transrectal ultrasound-guided prostate biopsies, were assessed. Analysis-modeling stage for several clinical indexes related to prostate cancer and renal function was carried out. Multiple logistic regression analyses were used to develop new risk assessment models of prostate cancer for both PSA level ranges 4-10 and 10-50 ng/mL. External validation stage of the new models was performed to assess the necessity of biopsy. The new models for both PSA ranges performed significantly better than PSA for detecting prostate cancers. Both models showed higher areas under the curves (0.937 and 0.873, respectively) compared with PSA alone (0.624 and 0.595), at pre-determined cut-off values of 0.1067 and 0.6183, respectively. Patients above the cut-off values were recommended for immediate biopsy, while the others were actively observed. External validation of the models showed significantly increased detection rates for prostate cancer (4-10 ng/mL group, 39.29% vs 17.79%, p=0.006; 10-50 ng/mL group, 71.83% vs 50.0%, p=0.015). We developed risk assessment models for North Chinese patients with 4-50 ng/mL PSA to reduce unnecessary prostate biopsies and increase the detection rate of prostate cancer.

Use of Aspirin and Other Nonsteroidal Antiinflammatory Medications in Relation to Prostate Cancer Risk

PubMed Central

Salinas, Claudia A.; Kwon, Erika M.; FitzGerald, Liesel M.; Feng, Ziding; Nelson, Peter S.; Ostrander, Elaine A.; Peters, Ulrike; Stanford, Janet L.

2010-01-01

Recent interest has focused on the role that inflammation may play in the development of prostate cancer and whether use of aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs) affects risk. In a population-based case-control study designed to investigate the relation between these medications and prostate cancer risk, detailed exposure data were analyzed from 1,001 cases diagnosed with prostate cancer between January 1, 2002, and December 31, 2005, and 942 age-matched controls from King County, Washington. A significant 21% reduction in the risk of prostate cancer was observed among current users of aspirin compared with nonusers (95% confidence interval (CI): 0.65, 0.96). Long-term use of aspirin (>5 years: odds ratio = 0.76, 95% CI: 0.61, 0.96) and daily use of low-dose aspirin (odds ratio = 0.71, 95% CI: 0.56, 0.90) were also associated with decreased risk. There was no evidence that the association with aspirin use varied by disease aggressiveness, but there was effect modification (Pinteraction = 0.02) with a genetic variant in prostaglandin-endoperoxide synthase 2 (PTGS2) (rs12042763). Prostate cancer risk was not related to use of either nonaspirin NSAIDs or acetaminophen. These results contribute further evidence that aspirin may have chemopreventive activity against prostate cancer and highlight the need for additional research. PMID:20688905

A large scale analysis of genetic variants within putative miRNA binding sites in prostate cancer

PubMed Central

Stegeman, Shane; Amankwah, Ernest; Klein, Kerenaftali; O’Mara, Tracy A.; Kim, Donghwa; Lin, Hui-Yi; Permuth-Wey, Jennifer; Sellers, Thomas A.; Srinivasan, Srilakshmi; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Olama, Ali Amin Al; Benlloch, Sara; Muir, Kenneth; Giles, Graham G.; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A.; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C.; Neal, David; Pharoah, Paul; Khaw, Kay-Tee; Stanford, Janet L.; Blot, William J.; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S.; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Kaneva, Radka; Teixeira, Manuel R.; Consortium, PRACTICAL; Spurdle, Amanda B.; Clements, Judith A.; Park, Jong Y.; Batra, Jyotsna

2015-01-01

Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies (GWAS) have identified 100 risk variants for prostate cancer, which can explain ~33% of the familial risk of the disease. We hypothesized that a comprehensive analysis of genetic variations found within the 3′ UTR of genes predicted to affect miRNA binding (miRSNPs) can identify additional prostate cancer risk variants. We investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 cases and 22,320 controls of European ancestry from 23 participating studies. Twenty-two miRSNPs were associated (p<2.3×10−5) with risk of prostate cancer, 10 of which were within the 7 genes previously not mapped by GWASs. Further, using miRNA mimics and reporter gene assays, we showed that miR-3162-5p has specific affinity for the KLK3 rs1058205 miRSNP T-allele whilst miR-370 has greater affinity for the VAMP8 rs1010 miRSNP A-allele, validating their functional role. Significance Findings from this large association study suggest that a focus on miRSNPs, including functional evaluation, can identify candidate risk loci below currently accepted statistical levels of genome-wide significance. Studies of miRNAs and their interactions with SNPs could provide further insights into the mechanisms of prostate cancer risk. PMID:25691096

Outcomes Associated With 3 Treatment Schedules of High-Dose-Rate Brachytherapy Monotherapy for Favorable-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jawad, Maha Saada; Dilworth, Joshua T.; Gustafson, Gary S.

Purpose: We report the outcomes associated with 3 high-dose-rate (HDR) brachytherapy regimens used as monotherapy for favorable-risk prostate cancer. Methods and Materials: Four hundred ninety-four patients with stage ≤T2b prostate cancer, Gleason score ≤7, and prostate-specific antigen levels ≤15 ng/mL underwent HDR brachytherapy as monotherapy. Of those, 319 received 38 Gy in 4 fractions, 79 received 24 Gy in 2 fractions, and 96 received 27 Gy in 2 fractions. Acute and chronic genitourinary (GU) and gastrointestinal (GI) toxicities were defined as side effects occurring ≤6 and >6 months, respectively, after radiation therapy (RT) and were graded according to the Common Terminology Criteria for Adverse Events version 3.0.more » The time to toxicity was calculated from the date of RT completion. Variables were analyzed with χ{sup 2} test. P values <.05 were considered significant. Results: The median overall follow-up time was 4 years (range, 5.5, 3.5, and 2.5 years for 38 Gy, 24 Gy, and 27 Gy, respectively, P<.001). Acute and chronic grade ≥2 GU and GI toxicity profiles were similar among groups. Acceptable rates of grade 2 GU toxicities were seen with overall acute/chronic frequency/urgency, dysuria, retention, incontinence, and hematuria rates of 14%/20%, 6%/7%, 7%/4%, 1.5%/2%, and 1.5%/7%, respectively. Minimal grade 3 and no grade 4 or 5 toxicities were seen. Grade 1, 2, and 3 chronic urethral stricture rates were 0.3%, 2%, and 1%, respectively. All GI toxicities were similar between groups, with overall rates of acute/chronic grade 2 diarrhea, rectal pain/tenesmus, rectal bleeding, and proctitis of 1%/1%, <1%/0.5%, 0%/2%, and <1%/1%, respectively. No grade 3, 4, or 5 toxicities were seen. All comparisons were similar for hormone-naïve patients. The median time to maximal GU/GI toxicity was similar between groups, ranging from 1 to 1.6 to 0.9 to 1.2 years, respectively. There were no differences in clinical outcomes between the 3 groups at 5 years. Conclusions: The acute and chronic toxicity profiles associated with these 3 HDR brachytherapy schedules were similar and were well tolerated. Acceptable grade 2, minimal grade 3, and no grade 4 or 5 toxicities were seen. This, combined with the fact that the clinical outcomes were similar, leads to the conclusion that all 3 regimens may be acceptable options for the management of low-risk to intermediate-risk prostate cancer.« less

Estrogen receptor alpha polymorphisms and the risk of prostate cancer development.

PubMed

Jurečeková, Jana; Babušíková, Eva; Kmeťová, Monika; Kliment, Ján; Dobrota, Dušan

2015-11-01

The main purpose of the study was to evaluate the effect of two polymorphisms in the estrogen receptor alpha, rs2077647 and rs3798577, on the development of prostate cancer, their correlation with selected clinical characteristics, as well as consideration of potential interactions between four estrogen receptor alpha polymorphisms (rs2077647, rs3798577, PvuII, XbaI). The study was performed using 395 patients with histologically verified prostate cancer and 253 healthy male controls. The CC genotype of rs2077647 was significantly associated with prostate cancer (OR = 1.61). No association was found between rs3798577 polymorphism and prostate cancer. After stratification of patients according to the age at diagnosis and Gleason score, we observed significant correlation between rs2077647 polymorphism and prostate cancer risk in patients diagnosed before the age of 60 as well as patients with Gleason score <7, while rs3798577 was significantly associated with prostate cancer risk development in patients older than 60 and with Gleason score ≥7. Double analysis of each combination of four studied polymorphisms showed that presence of at least three variant alleles was associated with prostate cancer risk in all combinations, while each containing rs3798577 was significantly associated with development of high-grade carcinomas. The present study suggests that rs2077647 polymorphism may be a risk factor for prostate cancer especially in patients diagnosed before the age of 60, while rs3798577 polymorphism could probably serve rather as promoting factor in combination with other polymorphisms in estrogen receptor alpha contributing preferably to development of high-grade carcinomas.

Human Papilloma Virus Detection by INNOLiPA HPV in Prostate Tissue from Men of Northeast Mexico

PubMed

Dávila-Rodríguez, Martha I; Ignacio Morales, Cesar V; Aragón Tovar, Anel R; Olache Jimenez, Delia; Castelán Maldonado, Edmundo; Lara Miranda, Sandra; Cortés Gutiérrez, Elva I

2016-11-01

Background: Prostatic adenocarcinoma by Prosate cancer (PCa) is the most prevalent cancer and the second cause of cancer-related death among men in the Western world. Human papilloma virus (HPV) may be considered as a preventable risk factor. In this study, we assessed the frequencies of HPV infection in prostatic adenocarcinoma and benign prostatic hyperplasia (BPH) cases in Northeast Mexico. Materials and Methods: A total of 87 paraffin-embedded blocks (from 25 and 62 patients with definite diagnoses of BPH and adenocarcinoma, respectively) were selected and subjected to INNOLiPA HPV Genotyping to detect 28 high- and low-risk HPV types. The rates of infection were compared in the two studied groups. Results: INNOLiPA HPV demonstrated great sensitivity for HPV detection on paraffin-embedded tissue. Global prevalence was 14.9% (13/87). HPV infection was positive in 19.4% (12/62) of patients with adenocarcinoma and 4.0% (1/25) of patients with BPH. HPV-11, which is considered to be low risk, was more prevalent. Interestingly, one patient with BPH and six with prostate cancer showed examples considered to be high risk (HPV-18, -51, -52, and -66). Conclusion: A higher rate of HPV infection among Mexican patients with prostatic carcinoma than among those with BPH was observed. HPV infections may thus contribute to the risk of prostate cancer. Further studies are required to elucidate any roles of HPV infection in prostate disease in Mexico and the effect of prevention and treatment of HPV infection on prostatic adenocarcinoma. Creative Commons Attribution License

Human Papilloma Virus Detection by INNOLiPA HPV in Prostate Tissue from Men of Northeast Mexico

PubMed Central

Rodriguez, Martha I Dávila; Morales, Cesar V Ignacio; Tovar, Anel R Aragón; Jimenez, Delia Olache; Maldonado, Edmundo Castelán; Miranda, Sandra Lara; Gutiérrez, Elva I Cortés

2016-01-01

Background: Prostatic adenocarcinoma by Prosate cancer (PCa) is the most prevalent cancer and the second cause of cancer-related death among men in the Western world. Human papilloma virus (HPV) may be considered as a preventable risk factor. In this study, we assessed the frequencies of HPV infection in prostatic adenocarcinoma and benign prostatic hyperplasia (BPH) cases in Northeast Mexico. Materials and Methods: A total of 87 paraffin-embedded blocks (from 25 and 62 patients with definite diagnoses of BPH and adenocarcinoma, respectively) were selected and subjected to INNOLiPA HPV Genotyping to detect 28 high- and low-risk HPV types. The rates of infection were compared in the two studied groups. Results: INNOLiPA HPV demonstrated great sensitivity for HPV detection on paraffin-embedded tissue. Global prevalence was 14.9% (13/87). HPV infection was positive in 19.4% (12/62) of patients with adenocarcinoma and 4.0% (1/25) of patients with BPH. HPV-11, which is considered to be low risk, was more prevalent. Interestingly, one patient with BPH and six with prostate cancer showed examples considered to be high risk (HPV-18, -51, -52, and -66). Conclusion: A higher rate of HPV infection among Mexican patients with prostatic carcinoma than among those with BPH was observed. HPV infections may thus contribute to the risk of prostate cancer. Further studies are required to elucidate any roles of HPV infection in prostate disease in Mexico and the effect of prevention and treatment of HPV infection on prostatic adenocarcinoma. PMID:28030912

Prostate cancer: The main risk and protective factors-Epigenetic modifications.

PubMed

Adjakly, Mawussi; Ngollo, Marjolaine; Dagdemir, Aslihan; Judes, Gaëlle; Pajon, Amaury; Karsli-Ceppioglu, Seher; Penault-Llorca, Frédérique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

2015-02-01

With 13 million new cases worldwide every year, prostate cancer is as a very real public health concern. Prostate cancer is common in over-50s men and the sixth-leading cause of cancer-related death in men worldwide. Like all cancers, prostate cancer is multifactorial - there are non-modifiable risk factors like heredity, ethnicity and geographic location, but also modifiable risk factors such as diet. Diet-cancer linkages have risen to prominence in the last few years, with accruing epidemiological data pointing to between-population incidence differentials in numerous cancers. Indeed, there are correlations between fat-rich diet and risk of hormone-dependent cancers like prostate cancer and breast cancer. Diet is a risk factor for prostate cancer, but certain micronutrients in specific diets are considered protective factors against prostate cancer. Examples include tomato lycopene, green tea epigallocatechin gallate, and soy phytoestrogens. These micronutrients are thought to exert cancer-protective effects via anti-oxidant pathways and inhibition of cell proliferation. Here, we focus in on the effects of phytoestrogens, and chiefly genistein and daidzein, which are the best-researched to date. Soy phytoestrogens are nonsteroid molecules whose structural similarity lends them the ability to mimic the effects of 17ß-estradiol. On top of anti-oxidant effects, there is evidence that soy phytoestrogens can modulate the epigenetic modifications found in prostate cancer. We also studied the impact of phytoestrogens on epigenetic modifications in prostate cancer, with special focus on DNA methylation, miRNA-mediated regulation and histone modifications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Benign Prostatic Hyperplasia and the Risk of Prostate Cancer and Bladder Cancer

PubMed Central

Dai, Xiaoyu; Fang, Xiangming; Ma, Ying; Xianyu, Jianbo

2016-01-01

Abstract Benign prostatic hyperplasia (BPH) has been suggested to be a risk factor for certain urologic cancers, but the current evidence is inconsistent. The aim of this study was to investigate the association between BPH and urologic cancers. MEDLINE, EMBASE, Cochrane Library, and Web of Science were searched for potential eligible studies. We included case-control studies or cohort studies, which evaluated the association between BPH and urologic cancers (including prostate cancer, bladder cancer, kidney cancer, testicular cancer, or penile cancer). Overall effect estimates were calculated using the DerSimonian–Laird method for a random-effects model. Summary effect-size was calculated as risk ratio (RR), together with the 95% confidence interval (CI). This systematic review included 16 case-control studies and 10 cohort studies evaluating the association of BPH and prostate or bladder cancer; we did not identify any study about other urologic cancers. Meta-analyses demonstrated that BPH was associated with an increased incidence of prostate cancer (case-control study: RR = 3.93, 95% CI = 2.18–7.08; cohort-study: RR = 1.41, 95% CI = 1.00–1.99) and bladder cancer (case-control study: RR = 2.50, 95% CI = 1.63–3.84; cohort-study: RR = 1.58, 95% CI = 1.28–1.95). Subgroup analysis by ethnicity suggested that the association between BPH and prostate cancer was much stronger in Asians (RR = 6.09, 95% CI = 2.96–12.54) than in Caucasians (RR = 1.54, 95% CI = 1.19–2.01). Egger's tests indicated low risk of publication bias (prostate cancer: P = 0.11; bladder cancer: P = 0.95). BPH is associated with an increased risk of prostate cancer and bladder cancer. The risk of prostate cancer is particularly high in Asian BPH patients. Given the limitations of included studies, additional prospective studies with strict design are needed to confirm our findings. PMID:27149447

Association of Androgen Metabolism Gene Polymorphisms with Prostate Cancer Risk and Androgen Concentrations: Results from the Prostate Cancer Prevention Trial

PubMed Central

Price, Douglas K.; Chau, Cindy H.; Till, Cathee; Goodman, Phyllis J.; Leach, Robin J.; Johnson-Pais, Teresa L.; Hsing, Ann W.; Hoque, Ashraful; Parnes, Howard L.; Schenk, Jeannette M.; Tangen, Catherine M.; Thompson, Ian M.; Reichardt, Juergen K.V.; Figg, William D.

2016-01-01

Background Prostate cancer is highly influenced by androgens and genes. We investigated whether genetic polymorphisms along the androgen biosynthesis and metabolism pathways are associated with androgen concentrations or risk of prostate cancer or high-grade disease from finasteride treatment. Methods A nested case-control study from the Prostate Cancer Prevention Trial using cases drawn from men with biopsy-proven prostate cancer and biopsy-negative, frequency-matched controls was conducted to investigate the association of 51 single nucleotide polymorphisms (SNPs) in 12 genes of the androgen pathway with total, low-grade, and high-grade prostate cancer incidence and serum hormone concentrations. Results There were significant associations of genetic polymorphisms in SRD5A1 (rs3736316, rs3822430, rs1560149, rs248797, and rs472402) and SRD5A2 (rs2300700) with risk of high-grade prostate cancer in the placebo arm of the PCPT; two SNPs were significantly associated with increased risk (SRD5A1 rs472402 [OR, 1.70; 95% CI, 1.05-2.75, Ptrend=0.03]; SRD5A2 rs2300700 [OR, 1.94; 95% CI, 1.19-3.18, Ptrend=0.01]). Eleven SNPs in SRD5A1, SRD5A2, CYP1B1, and CYP3A4 were found to be associated with modifying mean serum androgen and sex hormone-binding globulin concentrations; two SNPs (SRD5A1 rs824811 and CYP1B1 rs10012, Ptrend<0.05) consistently and significantly altered all androgen concentrations. Several SNPs (rs3822430, rs2300700; CYP3A43 rs800672; CYP19 rs700519; Ptrend<0.05) were significantly associated with both circulating hormone levels and prostate cancer risk. Conclusion Germline genetic variations of androgen-related pathway genes are associated with serum androgen concentrations and risk of prostate cancer. Further studies to examine the functional consequence of novel causal variants are warranted. PMID:27164191

Body mass index in relation to serum prostate-specific antigen levels and prostate cancer risk.

PubMed

Bonn, Stephanie E; Sjölander, Arvid; Tillander, Annika; Wiklund, Fredrik; Grönberg, Henrik; Bälter, Katarina

2016-07-01

High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate-specific antigen (PSA). To study the association between BMI and serum PSA as well as prostate cancer risk, a large cohort of men without prostate cancer at baseline was followed prospectively for prostate cancer diagnoses until 2015. Serum PSA and BMI were assessed among 15,827 men at baseline in 2010-2012. During follow-up, 735 men were diagnosed with prostate cancer with 282 (38.4%) classified as high-grade cancers. Multivariable linear regression models and natural cubic linear regression splines were fitted for analyses of BMI and log-PSA. For risk analysis, Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) and natural cubic Cox regression splines producing standardized cancer-free probabilities were fitted. Results showed that baseline Serum PSA decreased by 1.6% (95% CI: -2.1 to -1.1) with every one unit increase in BMI. Statistically significant decreases of 3.7, 11.7 and 32.3% were seen for increasing BMI-categories of 25 < 30, 30 < 35 and ≥35 kg/m(2), respectively, compared to the reference (18.5 < 25 kg/m(2)). No statistically significant associations were seen between BMI and prostate cancer risk although results were indicative of a positive association to incidence rates of high-grade disease and an inverse association to incidence of low-grade disease. However, findings regarding risk are limited by the short follow-up time. In conclusion, BMI was inversely associated to PSA-levels. BMI should be taken into consideration when referring men to a prostate biopsy based on serum PSA-levels. © 2016 UICC.

SU-E-T-620: Dosimetric Compliance Study for a New Prostate Protocol of Combined High Dose Rate Brachytherapy and Stereotactic Body Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, C; Giaddui, T; Den, R

2014-06-15

Purpose: To investigate the adherence of treatment plans of prostate cancer patients with the dosimetric compliance criteria of the new in house phase I trial of high dose rate (HDR) brachytherapy combined with stereotactic body radiotherapy (SBRT) for intermediate risk prostate cancer patients. Methods: Ten prostate cancer patients were treated using this trial. They received one fraction of HDR to 15Gy, followed by external beam(EB) boost of 3.2Gy(Level 1, five patients) or 3.94Gy(level 2, five patients) per fraction for 10 or 7 fractions, respectively, both equivalent to EB treatments of 113.5Gy in 2Gy fractions. The EB plans were either IMRTmore » or VMAT plans. DVH analysis was performed to verify the adherence of treatment plans to the dosimetric criteria of the trial. Results: For Level 1 patients, target coverage were adequate, with CTV V32Gy(%) of 99.0±1.0 (mean ± 1 standard deviation), and PTV V31Gy(%) of 99.6±0.3. PTV V32.9Gy(%) is 1.4±3.1 and PTVmax is 32.9±0.2Gy. Rectum, bladder and femoral heads sparing were well within protocol criteria. For Level 2 patients, CTV V27.6Gy(%) is 98.7±1.8; PTV V26.7Gy(%) is 99.0±1.4. PTV V28.4Gy(%) is 1.3±1.4, with three patients having minor deviation from protocol. Again critical structures were spared compliant to the protocol. The analysis of HDR plans show similar results, with adequate dose coverage to the prostate and sparing of critical structures including urethra and rectum. V100(%) and V90(%) of prostate are 96.0±1.1 and 98.9±0.5. Urethra D10(%) is 113.1±2.9. Rectum V80(cc) is 1.4±0.5. Hotspot in prostate is substantially higher than what the protocol specifies. But the criteria for hotspot are only guidelines, serving to lower the dose to urethra . Conclusion: This new high biological equivalent dose prostate trial has been carried out successfully for ten patients. Based on dosimetric analysis, all HDR and external plans were compliant to the protocol criteria, with only minor deviations.« less

Synergistic interaction of benign prostatic hyperplasia and prostatitis on prostate cancer risk

PubMed Central

Hung, S-C; Lai, S-W; Tsai, P-Y; Chen, P-C; Wu, H-C; Lin, W-H; Sung, F-C

2013-01-01

Background: The incidence of prostate cancer is much lower in Asian men than in Western men. This study investigated whether prostate cancer is associated with prostatitis, benign prostatic hyperplasia (BPH), and other medical conditions in the low-incidence population. Methods: From the claims data obtained from the universal National Health Insurance of Taiwan, we identified 1184 patients with prostate cancer diagnosed from 1997 to 2008. Controls comprised 4736 men randomly selected from a cancer-free population. Both groups were 50 years of age or above. Medical histories between the two groups were compared. Results: Multivariate logistic regression analysis showed that prostatitis and BPH had stronger association with prostate cancer than the other medical conditions tested. Compared with men without prostatitis and BPH, a higher odds ratio (OR) for prostate cancer was associated with BPH (26.2, 95% confidence interval (CI) 20.8–33.0) than with prostatitis (10.5, 95% CI=3.36–32.7). Men with both conditions had an OR of 49.2 (95% CI=34.7–69.9). Conclusion: Men with prostate cancer have strong association with prostatitis and/or BPH. Prostatitis interacts with BPH, resulting in higher estimated relative risk of prostate cancer in men suffering from both conditions. PMID:23612451

CHEK2 (∗) 1100delC Mutation and Risk of Prostate Cancer.

PubMed

Hale, Victoria; Weischer, Maren; Park, Jong Y

2014-01-01

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer. CHEK2 plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, of CHEK2 on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussed CHEK2 (∗)1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23-3.18) for unselected cases and 3.39 (1.78-6.47) for familial cases, indicating that CHEK2 (∗)1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2(∗)1100delC should be considered in men with a familial history of prostate cancer.

CHEK2 ∗1100delC Mutation and Risk of Prostate Cancer

PubMed Central

Park, Jong Y.

2014-01-01

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer. CHEK2 plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, of CHEK2 on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussed CHEK2 ∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18) for unselected cases and 3.39 (1.78–6.47) for familial cases, indicating that CHEK2 ∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer. PMID:25431674

Vitamin E and selenium supplementation and risk of prostate cancer in the Vitamins and lifestyle (VITAL) study cohort.

PubMed

Peters, Ulrike; Littman, Alyson J; Kristal, Alan R; Patterson, Ruth E; Potter, John D; White, Emily

2008-02-01

Vitamin E and selenium are promising nutrients for the prevention of prostate cancer, and both are currently being tested in a large randomized trial for prostate cancer. However, results are not expected for at least 6 years. We aimed to investigate the association of vitamin E and selenium supplementation with prostate cancer in the VITamins And Lifestyle (VITAL) study, a cohort study specifically designed to examine supplement use and future cancer risk. In a prospective design, 35,242 men recruited between 2000 and 2002 from western Washington State completed a questionnaire, including detailed questions about vitamin E and selenium supplement intake during the past 10 years from brand-specific multivitamins and single supplements. Using linkage to the western Washington SEER cancer registry, we documented 830 new cases of prostate cancer from baseline through December 2004. A 10-year average intake of supplemental vitamin E was not associated with a reduced prostate cancer risk overall [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.65-1.1 for > or =400 IU/day vs. non-use, p for trend 0.36]; however, risk for advanced prostate cancer (regionally invasive or distant metastatic, n = 123) decreased significantly with greater intake of supplemental vitamin E (HR 0.43, 95% CI 0.19-1.0 for 10-year average intake > or =400 IU/day vs. non-use, p for trend 0.03). There was no association between selenium supplementation and prostate cancer risk (HR 0.90, 95% CI 0.62-1.3 for 10-year average intake >50 microg/day vs. non-use, p for trend 0.97). In this prospective cohort, long-term supplemental intake of vitamin E and selenium were not associated with prostate cancer risk overall; however, risk of clinically relevant advanced disease was reduced with greater long-term vitamin E supplementation.

Investigating the possible causal role of coffee consumption with prostate cancer risk and progression using Mendelian randomization analysis.

PubMed

Taylor, Amy E; Martin, Richard M; Geybels, Milan S; Stanford, Janet L; Shui, Irene; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Neal, David; Pashayan, Nora; Khaw, Kay-Tee; Blot, William; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Donovan, Jenny; Munafò, Marcus R

2017-01-15

Coffee consumption has been shown in some studies to be associated with lower risk of prostate cancer. However, it is unclear if this association is causal or due to confounding or reverse causality. We conducted a Mendelian randomisation analysis to investigate the causal effects of coffee consumption on prostate cancer risk and progression. We used two genetic variants robustly associated with caffeine intake (rs4410790 and rs2472297) as proxies for coffee consumption in a sample of 46,687 men of European ancestry from 25 studies in the PRACTICAL consortium. Associations between genetic variants and prostate cancer case status, stage and grade were assessed by logistic regression and with all-cause and prostate cancer-specific mortality using Cox proportional hazards regression. There was no clear evidence that a genetic risk score combining rs4410790 and rs2472297 was associated with prostate cancer risk (OR per additional coffee increasing allele: 1.01, 95% CI: 0.98,1.03) or having high-grade compared to low-grade disease (OR: 1.01, 95% CI: 0.97,1.04). There was some evidence that the genetic risk score was associated with higher odds of having nonlocalised compared to localised stage disease (OR: 1.03, 95% CI: 1.01, 1.06). Amongst men with prostate cancer, there was no clear association between the genetic risk score and all-cause mortality (HR: 1.00, 95% CI: 0.97,1.04) or prostate cancer-specific mortality (HR: 1.03, 95% CI: 0.98,1.08). These results, which should have less bias from confounding than observational estimates, are not consistent with a substantial effect of coffee consumption on reducing prostate cancer incidence or progression. © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Prevalence of and Risk Factors for Asymptomatic Inflammatory (NIH-IV) Prostatitis in Chinese Men

PubMed Central

Wu, Chunlei; Zhang, Zhifu; Lu, Zheng; Liao, Ming; Zhang, Youjie; Xie, Yuanliang; Guo, Xuefeng; Yu, Xiaoxiang; Yang, Xiaobo; Gao, Yong; Tan, Aihua; Mo, Zengnan

2013-01-01

Background While many investigators have studied symptomatic prostatitis, little research has been done with regard to asymptomatic (NIH-IV) prostatitis. Purpose To describe the prevalence of and risk factors for NIH-IV prostatitis among a large male population. Methods The study population was comprised of 1,868 men at the second phase recruitment of a population-based cohort in China. Asymptomatic and symptomatic men were defined by the National Institutes of Health Chronic Prostatitis (CP) Symptom Index. Meanwhile, EPS specimens and their leukocyte count were collected. Lifestyle and demographic characteristics were obtained through a questionnaire. Results Prevalence of NIH-IV prostatitis was 21.1% among 1,868 asymptomatic men aged 19–78 years and increased with age. After adjusteing for potential confounding variables (age, smoking habits, alcohol drinking habits, education, physical activity, hypertension, dyslipidemia, obesity and diabetes), age remained a significant factor for NIH-IV prostatitis (OR = 1.35; 95% CI = 1.06–1.71; P = 0.01) and the risk of NIH-IV prostatitis was significantly higher in smokers≧15 pack/years than non-smokers (OR = 1.33; 95% CI = 1.01–1.75; P = 0.03). In addition, compared with non-drinkers, the OR of NIH-IV prostatitis in drinkers ≧1 drinks/week was 1.35 (95% CI = 1.03, 1.77, p = 0.02) after adjusting for the other variables above. In addition, having less than a college education may be a risk factor for NIH-IV prostatitis, although a statistically significant difference did not exist in our data (OR = 1.22; 95% CI = 0.97–1.52; P = 0.08). Conclusions Our findings suggest that NIH-IV prostatitis is prevalent in China. Age, smoking, drinking and lower education levels were associated with an increased risk of NIH-IV prostatitis. The prevalence of NIH-IV prostatitis should be taken into account when estimating the total prevalence of CP in future studies. PMID:23967188

Larger men have larger prostates: Detection bias in epidemiologic studies of obesity and prostate cancer risk

PubMed Central

Rundle, Andrew; Wang, Yun; Sadasivan, Sudha; Chitale, Dhananjay A.; Gupta, Nilesh S.; Tang, Deliang; Rybicki, Benjamin A.

2017-01-01

BACKGROUND Obesity is associated with risk of aggressive prostate cancer (PCa), but not with over-all PCa risk. However, obese men have larger prostates which may lower biopsy accuracy and cause a systematic bias towards the null in epidemiologic studies of over-all risk. METHODS Within a cohort of 6,692 men followed-up after a biopsy or transurethral resection of the prostate (TURP) with benign findings, a nested case-control study was conducted of 495 prostate cancer cases and controls matched on age, race, follow-up duration, biopsy versus TURP and procedure date. Data on body mass index and prostate volume at the time of the initial procedure were abstracted from medical records. RESULTS Prior to consideration of differences in prostate volume, overweight (OR = 1.41; 95% CI 1.01, 1.97) and obese status (OR = 1.59; 95% CI 1.09, 2.33) at the time of the original benign biopsy or TURP were associated with PCa incidence during follow-up. Prostate volume did not significantly moderate the association between body-size and PCa, however it did act as an inverse confounder; adjustment for prostate volume increased the effect size for overweight by 22% (adjusted OR = 1.52; 95% CI 1.08, 2.14) and for obese status by 23% (adjusted OR = 1.77; 95% CI 1.20, 2.62). Larger prostate volume at the time of the original benign biopsy or TURP was inversely associated with PCa incidence during follow-up (OR = 0.92 per 10 cc difference in volume; 95% CI 0.88, 0.97). In analyses that stratified case-control pairs by tumor aggressiveness of the case, prostate volume acted as an inverse confounder in analyses of non-aggressive PCa but not in analyses of aggressive PCa. CONCLUSIONS In studies of obesity and PCa, differences in prostate volume cause a bias towards the null, particularly in analyses of non-aggressive PCa. A pervasive underestimation of the association between obesity and overall PCa risk may exist in the literature. PMID:28349547

Larger men have larger prostates: Detection bias in epidemiologic studies of obesity and prostate cancer risk.

PubMed

Rundle, Andrew; Wang, Yun; Sadasivan, Sudha; Chitale, Dhananjay A; Gupta, Nilesh S; Tang, Deliang; Rybicki, Benjamin A

2017-06-01

Obesity is associated with risk of aggressive prostate cancer (PCa), but not with over-all PCa risk. However, obese men have larger prostates which may lower biopsy accuracy and cause a systematic bias toward the null in epidemiologic studies of over-all risk. Within a cohort of 6692 men followed-up after a biopsy or transurethral resection of the prostate (TURP) with benign findings, a nested case-control study was conducted of 495 prostate cancer cases and controls matched on age, race, follow-up duration, biopsy versus TURP, and procedure date. Data on body mass index and prostate volume at the time of the initial procedure were abstracted from medical records. Prior to consideration of differences in prostate volume, overweight (OR = 1.41; 95%CI 1.01, 1.97), and obese status (OR = 1.59; 95%CI 1.09, 2.33) at the time of the original benign biopsy or TURP were associated with PCa incidence during follow-up. Prostate volume did not significantly moderate the association between body-size and PCa, however it did act as an inverse confounder; adjustment for prostate volume increased the effect size for overweight by 22% (adjusted OR = 1.52; 95%CI 1.08, 2.14) and for obese status by 23% (adjusted OR = 1.77; 95%CI 1.20, 2.62). Larger prostate volume at the time of the original benign biopsy or TURP was inversely associated with PCa incidence during follow-up (OR = 0.92 per 10 cc difference in volume; 95%CI 0.88, 0.97). In analyses that stratified case-control pairs by tumor aggressiveness of the case, prostate volume acted as an inverse confounder in analyses of non-aggressive PCa but not in analyses of aggressive PCa. In studies of obesity and PCa, differences in prostate volume cause a bias toward the null, particularly in analyses of non-aggressive PCa. A pervasive underestimation of the association between obesity and overall PCa risk may exist in the literature. © 2017 Wiley Periodicals, Inc.

Use of Digital Rectal Examination as an Adjunct to Prostate Specific Antigen in the Detection of Clinically Significant Prostate Cancer.

PubMed

Halpern, Joshua A; Oromendia, Clara; Shoag, Jonathan E; Mittal, Sameer; Cosiano, Michael F; Ballman, Karla V; Vickers, Andrew J; Hu, Jim C

2018-04-01

Guidelines from the NCCN ® (National Comprehensive Cancer Network®) advocate digital rectal examination screening only in men with elevated prostate specific antigen. We investigated the effect of prostate specific antigen on the association of digital rectal examination and clinically significant prostate cancer in a large American cohort. We evaluated the records of the 35,350 men who underwent digital rectal examination in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial for the development of clinically significant prostate cancer (Gleason 7 or greater). Followup was 343,273 person-years. The primary outcome was the rate of clinically significant prostate cancer among men with vs without suspicious digital rectal examination. We performed competing risks regression to evaluate the interaction between time varying suspicious digital rectal examination and prostate specific antigen. A total of 1,713 clinically significant prostate cancers were detected with a 10-year cumulative incidence of 5.9% (95% CI 5.6-6.2). Higher risk was seen for suspicious vs nonsuspicious digital rectal examination. Increases in absolute risk were small and clinically irrelevant for normal (less than 2 ng/ml) prostate specific antigen (1.5% vs 0.7% risk of clinically significant prostate cancer at 10 years), clinically relevant for elevated (3 ng/ml or greater) prostate specific antigen (23.0% vs 13.7%) and modestly clinically relevant for equivocal (2 to 3 ng/ml) prostate specific antigen (6.5% vs 3.5%). Digital rectal examination demonstrated prognostic usefulness when prostate specific antigen was greater than 3 ng/ml, limited usefulness for less than 2 ng/ml and marginal usefulness for 2 to 3 ng/ml. These findings support the restriction of digital rectal examination to men with higher prostate specific antigen as a reflex test to improve specificity. It should not be used as a primary screening modality to improve sensitivity. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

GIT2 Gene: Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions

DTIC Science & Technology

2014-05-01

survival of growth factor–expressing ASCs, which enter the systemic circulation and promote PCa progression. An important note is that the prostate...surgical castration and systemic GLIPR1-ΔTM in vivo using VCaP xenograft model: 1. Generate orthotopic VCaP tumors in athymic nude male mice and...effects of systemic GLIPR1-ΔTM on orthotopic VCaP tumor growth and ASCs infiltration profiles ± surgical castration at acute (3d), intermediate (14d

A survival model for fractionated radiotherapy with an application to prostate cancer

NASA Astrophysics Data System (ADS)

Zaider, Marco; Zelefsky, Michael J.; Hanin, Leonid G.; Tsodikov, Alexander D.; Yakovlev, Andrei Y.; Leibel, Steven A.

2001-10-01

This paper explores the applicability of a mechanistic survival model, based on the distribution of clonogens surviving a course of fractionated radiation therapy, to clinical data on patients with prostate cancer. The study was carried out using data on 1100 patients with clinically localized prostate cancer who were treated with three-dimensional conformal radiation therapy. The patients were stratified by radiation dose (group 1: <67.5 Gy; group 2: 67.5-72.5 Gy; group 3: 72.5-77.5 Gy; group 4: 77.5-87.5 Gy) and prognosis category (favourable, intermediate and unfavourable as defined by pre-treatment PSA and Gleason score). A relapse was recorded when tumour recurrence was diagnosed or when three successive prostate specific antigen (PSA) elevations were observed from a post-treatment nadir PSA level. PSA relapse-free survival was used as the primary end point. The model, which is based on an iterated Yule process, is specified in terms of three parameters: the mean number of tumour clonogens that survive the treatment, the mean of the progression time of post-treatment tumour development and its standard deviation. The model parameters were estimated by the maximum likelihood method. The fact that the proposed model provides an excellent description both of the survivor function and of the hazard rate is prima facie evidence of the validity of the model because closeness of the two survivor functions (empirical and model-based) does not generally imply closeness of the corresponding hazard rates. The estimated cure probabilities for the favourable group are 0.80, 0.74 and 0.87 (for dose groups 1-3, respectively); for the intermediate group: 0.25, 0.51, 0.58 and 0.78 (for dose groups 1-4, respectively) and for the unfavourable group: 0.0, 0.27, 0.33 and 0.64 (for dose groups 1-4, respectively). The distribution of progression time to tumour relapse was found to be independent of prognosis group but dependent on dose. As the dose increases the mean progression time decreases (41, 28.5, 26.2 and 14.7 months for dose groups 1-4, respectively). This analysis confirms that, in terms of cure rate, dose escalation has a significant positive effect only in the intermediate and unfavourable groups. It was found that progression time is inversely proportional to dose, which means that patients recurring in higher dose groups have shorter recurrence times, yet these groups have better survival, particularly long-term. The explanation for this seemingly illogical observation lies in the fact that less aggressive tumours, potentially recurring after a long period of time, are cured by higher doses and do not contribute to the recurrence pattern. As a result, patients in higher dose groups are less likely to recur; however, if they do, they tend to recur earlier. The estimated hazard rates for prostate cancer pass through a clear-cut maximum, thus revealing a time period with especially high values of instantaneous cancer-specific risk; the estimates appear to be nonproportional across dose strata.

Reduction by coffee consumption of prostate cancer risk: Evidence from the Moli-sani cohort and cellular models.

PubMed

Pounis, George; Tabolacci, Claudio; Costanzo, Simona; Cordella, Martina; Bonaccio, Marialaura; Rago, Livia; D'Arcangelo, Daniela; Filippo Di Castelnuovo, Augusto; de Gaetano, Giovanni; Donati, Maria Benedetta; Iacoviello, Licia; Facchiano, Francesco

2017-07-01

Meta-analytic data on the effect of coffee in prostate cancer risk are controversial. Caffeine as a bioactive compound of coffee has not yet been studied in deep in vitro. Our study aimed at evaluating in a population cohort the effect of Italian-style coffee consumption on prostate cancer risk and at investigating in vitro the potential antiproliferative and antimetastatic activity of caffeine on prostate cancer cell lines. 6,989 men of the Moli-sani cohort aged ≥50 years were followed for a mean of 4.24 ± 1.35 years and 100 new prostate cancer cases were identified. The European Prospective Investigation into Cancer and Nutrition-Food Frequency Questionnaire was used for the dietary assessment and the evaluation of Italian-style coffee consumption. Two human prostate cancer cell lines, PC-3 and DU145, were tested with increasing concentrations of caffeine, and their proliferative/metastatic features were evaluated. The newly diagnosed prostate cancer participants presented lower coffee consumption (60.1 ± 51.3 g/day) compared to the disease-free population (74.0 ± 51.7 g/day) (p < 0.05). Multiadjusted analysis showed that the subjects at highest consumption (>3 cups/day) had 53% lower prostate cancer risk as compared to participants at the lowest consumption (0-2 cups/day) (p = 0.02). Both human prostate cancer cell lines treated with caffeine showed a significant reduction in their proliferative and metastatic behaviors (p < 0.05). In conclusion, reduction by Italian-style coffee consumption of prostate cancer risk (>3 cups/day) was observed in epidemiological level. Caffeine appeared to exert both antiproliferative and antimetastatic activity on two prostate cancer cell lines, thus providing a cellular confirmation for the cohort study results. © 2017 UICC.

Acute Bacterial Prostatitis: Diagnosis and Management.

PubMed

Coker, Timothy J; Dierfeldt, Daniel M

2016-01-15

Acute bacterial prostatitis is an acute infection of the prostate gland that causes pelvic pain and urinary tract symptoms, such as dysuria, urinary frequency, and urinary retention, and may lead to systemic symptoms, such as fevers, chills, nausea, emesis, and malaise. Although the true incidence is unknown, acute bacterial prostatitis is estimated to comprise approximately 10% of all cases of prostatitis. Most acute bacterial prostatitis infections are community acquired, but some occur after transurethral manipulation procedures, such as urethral catheterization and cystoscopy, or after transrectal prostate biopsy. The physical examination should include abdominal, genital, and digital rectal examination to assess for a tender, enlarged, or boggy prostate. Diagnosis is predominantly made based on history and physical examination, but may be aided by urinalysis. Urine cultures should be obtained in all patients who are suspected of having acute bacterial prostatitis to determine the responsible bacteria and its antibiotic sensitivity pattern. Additional laboratory studies can be obtained based on risk factors and severity of illness. Radiography is typically unnecessary. Most patients can be treated as outpatients with oral antibiotics and supportive measures. Hospitalization and broad-spectrum intravenous antibiotics should be considered in patients who are systemically ill, unable to voluntarily urinate, unable to tolerate oral intake, or have risk factors for antibiotic resistance. Typical antibiotic regimens include ceftriaxone and doxycycline, ciprofloxacin, and piperacillin/tazobactam. The risk of nosocomial bacterial prostatitis can be reduced by using antibiotics, such as ciprofloxacin, before transrectal prostate biopsy.

High serum concentration of estradiol may be a risk factor of prostate enlargement in aging male in China.

PubMed

Xu, Ding; Wu, Yu; Shen, Haibo; Qian, Subo; Qi, Jun

2018-06-18

Assess the association between serum sex hormone level and prostate volume in men with benign prostatic hyperplasia (BPH). The study involved 239 BPH patients from January 2013 to June 2015 in our hospital. Each patient collected age, medical history, height, weight, body mass index, as well as a full examination of sex hormones, and transrectal ultrasound results. Estradiol (E2) was significantly associated with prostate volume (r = 0.151, p = .02) and transitional zone volume (r = 0.136, p = .035). The association was more significant after adjusting age and BMI (r = 0.253 and 0.250, p <.001). Patients were divided into two groups according to prostate volume and E2, respectively. E2 in patients with prostate volume ≤50 ml was significantly lower than those with prostate volume >50 ml. Prostate volume, transitional zone volume and age were all significantly higher in the patients with E2 ≥ 160 umol/l than those in the patients with E2 < 160 umol/l. Through logistics regression, E2 (p = .012, OR = 1.004) are the only independent risk factor for prostate volume. E2 is significantly associated with prostate volume. High concentrations of E2 may be a risk factor for the large volume of prostate.

Family history of breast cancer increases the risk of prostate cancer: results from the EPICAP study.

PubMed

Lamy, Pierre-Jean; Trétarre, Brigitte; Rebillard, Xavier; Sanchez, Marie; Cénée, Sylvie; Ménégaux, Florence

2018-05-04

Familial aggregation is now well established with an increased risk of prostate cancer in patients with a family history of prostate cancer in first degree relatives. The aim of this paper was to investigate the role of family history of cancer in first degree relatives in prostate cancer risk. As expected, a family history of prostate cancer in first-degree relatives was more frequent in cases than in controls (OR 3.10, 95% CI 2.32-4.15). A family history of early BCa (before age 50) in first-degree relatives was more frequent in cases than in controls (OR 1.79, 95% CI 1.09-2.94) with higher risk of aggressive PCa. The association was more pronounced for BCa in daughters (OR 15.26 95% CI 1.95-120). In summary, a family history of BCa in first degree relatives before age 50 may increases the risk of PCa with higher Gleason score. This finding could suggest a specific prostate surveillance and/or genetic counselling for men who present such familial history. EPIdemiological study of Prostate CAncer (EPICAP) is a population-based case-control study specifically designed to investigate the role of environmental and genetic factors in prostate cancer. Detailed information on family history of cancer in first degree relatives (parents, brothers and sisters, children) was collected as well as the age of occurrence and the localization of each cancer. Overall, 819 cases and 879 controls have been included.

USE OF AGRICULTURAL PESTICIDES AND PROSTATE CANCER RISK IN THE AGRICULTURAL HEALTH STUDY COHORT

EPA Science Inventory

The role of specific agricultural chemicals in relation to prostate cancer risk has not been firmly established due to the lack of precise exposure data. We examined the relationship between 45 common agricultural pesticides and prostate cancer incidence in a prospective cohor...

Longitudinal Association between Prostatitis and Development of Benign Prostatic Hyperplasia

PubMed Central

St. Sauver, Jennifer L.; Jacobson, Debra J.; McGree, Michaela E.; Girman, Cynthia J.; Lieber, Michael M.; Jacobsen, Steven J.

2008-01-01

OBJECTIVES To determine whether physician-diagnosed prostatitis was associated with later development of development of BPH-associated events in a longitudinal, population-based sample of 2447 men residing in Olmsted County, Minnesota. METHODS Medical records were reviewed for physician diagnosis of prostatitis and subsequent diagnoses of BPH, enlarged prostate, prostatism, and acute urinary retention. Records were also reviewed for medical or surgical treatments for BPH. Odds ratios were calculated to assess the associations between physician-diagnosed prostatitis and later development of development of BPH-associated events. RESULTS Physician-diagnosed prostatitis was associated with a 2.4-fold increased odds of receiving a later diagnosis of prostatism, enlarged prostate, or BPH (OR: 2.44, 95% CI: 1.48, 4.01). Prostatitis was also associated with a 70% increased odds of requiring later treatment for BPH (OR: 1.69, 95% CI: 1.28, 2.22), and a non-significant increased odds of acute urinary retention (OR: 1.33, 95% CI: 0.89, 1.99). CONCLUSIONS Physician-diagnosed prostatitis was associated with an increased risk of later onset of several BPH-associated events. Physician-diagnosed prostatitis may therefore be an early marker or a risk factor for development of later prostatic or urologic problems. PMID:18342190

The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium.

PubMed

Davies, Neil M; Gaunt, Tom R; Lewis, Sarah J; Holly, Jeff; Donovan, Jenny L; Hamdy, Freddie C; Kemp, John P; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Neal, David; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Lathrop, Mark; Smith, George Davey; Martin, Richard M

2015-11-01

Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality. We conducted a case-control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man's number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies. The genetic risk scores explained 6.31 and 1.46% of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95% CI 0.96, 1.00; p = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95% CI 0.97, 1.01; p = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (p heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (p heterogeneity = 0.03). We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication.

Development and External Validation of the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer: Comparison with Two Western Risk Calculators in an Asian Cohort

PubMed Central

Yoon, Sungroh; Park, Man Sik; Choi, Hoon; Bae, Jae Hyun; Moon, Du Geon; Hong, Sung Kyu; Lee, Sang Eun; Park, Chanwang

2017-01-01

Purpose We developed the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer (KPCRC-HG) that predicts the probability of prostate cancer (PC) of Gleason score 7 or higher at the initial prostate biopsy in a Korean cohort (http://acl.snu.ac.kr/PCRC/RISC/). In addition, KPCRC-HG was validated and compared with internet-based Western risk calculators in a validation cohort. Materials and Methods Using a logistic regression model, KPCRC-HG was developed based on the data from 602 previously unscreened Korean men who underwent initial prostate biopsies. Using 2,313 cases in a validation cohort, KPCRC-HG was compared with the European Randomized Study of Screening for PC Risk Calculator for high-grade cancer (ERSPCRC-HG) and the Prostate Cancer Prevention Trial Risk Calculator 2.0 for high-grade cancer (PCPTRC-HG). The predictive accuracy was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots. Results PC was detected in 172 (28.6%) men, 120 (19.9%) of whom had PC of Gleason score 7 or higher. Independent predictors included prostate-specific antigen levels, digital rectal examination findings, transrectal ultrasound findings, and prostate volume. The AUC of the KPCRC-HG (0.84) was higher than that of the PCPTRC-HG (0.79, p<0.001) but not different from that of the ERSPCRC-HG (0.83) on external validation. Calibration plots also revealed better performance of KPCRC-HG and ERSPCRC-HG than that of PCPTRC-HG on external validation. At a cut-off of 5% for KPCRC-HG, 253 of the 2,313 men (11%) would not have been biopsied, and 14 of the 614 PC cases with Gleason score 7 or higher (2%) would not have been diagnosed. Conclusions KPCRC-HG is the first web-based high-grade prostate cancer prediction model in Korea. It had higher predictive accuracy than PCPTRC-HG in a Korean population and showed similar performance with ERSPCRC-HG in a Korean population. This prediction model could help avoid unnecessary biopsy and reduce overdiagnosis and overtreatment in clinical settings. PMID:28046017

Development and External Validation of the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer: Comparison with Two Western Risk Calculators in an Asian Cohort.

PubMed

Park, Jae Young; Yoon, Sungroh; Park, Man Sik; Choi, Hoon; Bae, Jae Hyun; Moon, Du Geon; Hong, Sung Kyu; Lee, Sang Eun; Park, Chanwang; Byun, Seok-Soo

2017-01-01

We developed the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer (KPCRC-HG) that predicts the probability of prostate cancer (PC) of Gleason score 7 or higher at the initial prostate biopsy in a Korean cohort (http://acl.snu.ac.kr/PCRC/RISC/). In addition, KPCRC-HG was validated and compared with internet-based Western risk calculators in a validation cohort. Using a logistic regression model, KPCRC-HG was developed based on the data from 602 previously unscreened Korean men who underwent initial prostate biopsies. Using 2,313 cases in a validation cohort, KPCRC-HG was compared with the European Randomized Study of Screening for PC Risk Calculator for high-grade cancer (ERSPCRC-HG) and the Prostate Cancer Prevention Trial Risk Calculator 2.0 for high-grade cancer (PCPTRC-HG). The predictive accuracy was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots. PC was detected in 172 (28.6%) men, 120 (19.9%) of whom had PC of Gleason score 7 or higher. Independent predictors included prostate-specific antigen levels, digital rectal examination findings, transrectal ultrasound findings, and prostate volume. The AUC of the KPCRC-HG (0.84) was higher than that of the PCPTRC-HG (0.79, p<0.001) but not different from that of the ERSPCRC-HG (0.83) on external validation. Calibration plots also revealed better performance of KPCRC-HG and ERSPCRC-HG than that of PCPTRC-HG on external validation. At a cut-off of 5% for KPCRC-HG, 253 of the 2,313 men (11%) would not have been biopsied, and 14 of the 614 PC cases with Gleason score 7 or higher (2%) would not have been diagnosed. KPCRC-HG is the first web-based high-grade prostate cancer prediction model in Korea. It had higher predictive accuracy than PCPTRC-HG in a Korean population and showed similar performance with ERSPCRC-HG in a Korean population. This prediction model could help avoid unnecessary biopsy and reduce overdiagnosis and overtreatment in clinical settings.

Prospective Quality of Life in Men Choosing Active Surveillance Compared to Those Biopsied but not Diagnosed with Prostate Cancer.

PubMed

Pham, Khanh N; Cullen, Jennifer; Hurwitz, Lauren M; Wolff, Erika M; Levie, Katherine E; Odem-Davis, Katherine; Banerji, John S; Rosner, Inger L; Brand, Timothy C; L'Esperance, James O; Sterbis, Joseph R; Porter, Christopher R

2016-08-01

Active surveillance is an important alternative to definitive therapy for men with low risk prostate cancer. However, the impact of active surveillance on health related quality of life compared to that in men without cancer remains unknown. In this study we evaluated health related quality of life outcomes in men on active surveillance compared to men followed after negative prostate needle biopsy. A prospective study was conducted on men who were enrolled into the Center for Prostate Disease Research Multicenter National Database and underwent prostate needle biopsy for suspicion of prostate cancer between 2007 and 2014. Health related quality of life was assessed at biopsy (baseline) and annually for up to 3 years using SF-36 and EPIC questionnaires. Health related quality of life scores were modeled using generalized estimating equations, adjusting for baseline health related quality of life, and demographic and clinical characteristics. Of the 1,204 men who met the initial eligibility criteria 420 had a negative prostate needle biopsy (noncancer comparison group). Among the 411 men diagnosed with low risk prostate cancer 89 were on active surveillance. Longitudinal analysis revealed that for most health related quality of life subscales there were no significant differences between the groups in adjusted health related quality of life score trends over time. In this study most health related quality of life outcomes in patients with low risk prostate cancer on active surveillance did not differ significantly from those of men without prostate cancer. A comparison group of men with a similar risk of prostate cancer detection is critical to clarify the psychological and physical impact of active surveillance. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The Relationship of Baseline Prostate Specific Antigen and Risk of Future Prostate Cancer and Its Variance by Race.

PubMed

Verges, Daniel P; Dani, Hasan; Sterling, William A; Weedon, Jeremy; Atallah, William; Mehta, Komal; Schreiber, David; Weiss, Jeffrey P; Karanikolas, Nicholas T

2017-01-01

Several studies suggest that a baseline prostate specific antigen (PSA) measured in young men predicts future risk of prostate cancer. Considering recent recommendations against PSA screening, high-risk populations (e.g. black men, men with a high baseline PSA) may be particularly vulnerable in the coming years. Thus, we investigated the relationship between baseline PSA and future prostate cancer in a black majority-minority urban population. A retrospective analysis was performed of the prostate biopsy database (n = 994) at the Brooklyn Veterans Affairs Hospital. These men were referred to urology clinic for elevated PSA and biopsied between 2007 and 2014. Multivariate logistic regression was used to predict positive prostate biopsy from log-transformed baseline PSA, race (black, white, or other), and several other variables. The majority of men identified as black (50.2%). Median age at time of baseline PSA and biopsy was 58.6 and 64.8, respectively. Median baseline PSA was similar among black men and white men (2.70 vs 2.91 for black men vs white men, p = 0.232). Even so, black men were more likely than white men to be diagnosed with prostate cancer (OR 1.62, p < 0.0001). Black men less than age 70 were at particularly greater risk than their white counterparts. Baseline PSA was not a statistically significant predictor of future prostate cancer (p = 0.101). Black men were more likely to be diagnosed with prostate cancer than were white men, despite comparable baseline PSA. In our pre-screened population at the urology clinic, a retrospective examination of baseline PSA did not predict future prostate cancer. Copyright © 2016 National Medical Association. Published by Elsevier Inc. All rights reserved.

Endocrine disruptors and prostate cancer risk

PubMed Central

Prins, Gail S

2010-01-01

There is increasing evidence both from epidemiology studies and animal models that specific endocrine-disrupting compounds may influence the development or progression of prostate cancer. In large part, these effects appear to be linked to interference with estrogen signaling, either through interacting with ERs or by influencing steroid metabolism and altering estrogen levels within the body. In humans, epidemiologic evidence links specific pesticides, PCBs and inorganic arsenic exposures to elevated prostate cancer risk. Studies in animal models also show augmentation of prostate carcinogenesis with several other environmental estrogenic compounds including cadmium, UV filters and BPA. Importantly, there appears to be heightened sensitivity of the prostate to these endocrine disruptors during the critical developmental windows including in utero and neonatal time points as well as during puberty. Thus infants and children may be considered a highly susceptible population for ED exposures and increased risk of prostate cancers with aging. PMID:18524946

Cryotherapy for primary treatment of prostate cancer: intermediate term results of a prospective study from a single institution.

PubMed

Rodríguez, S Alvarez; Arias Fúnez, F; Bueno Bravo, C; Rodríguez-Patrón Rodríguez, R; Sanz Mayayo, E; Palacios, V Hevia; Burgos Revilla, F J

2014-01-01

Purpose. Published data about cryotherapy for prostate cancer (PC) treatment are based on case series with a lack of clinical trials and the inexistence of a validated definition of biochemical failure. A prospective study with standardized followup protocol was conducted in our institution. Material and Methods. Prospective study of a series of cases including 108 patients diagnosed with localized PC at clinical stage T1c-T2c treated by primary cryoablation and median followup of 61 months. Criteria of biochemical recurrence were unified according to the American Society for Therapeutic Radiology and Oncology (ASTRO). End points were biochemical progression-free survival (BPFS), cancer-specific survival, and overall survival. Rate of complications was reported. Results. The BPFS for low-, medium-, and high-risk patients was 96.4%, 91.2%, and 62.2%, respectively. Cancer-specific survival was 98.1%. Overall survival reached 94.4%. Complications included incontinence in 5.6%, urinary tract obstruction in 1.9%, urethral sloughing in 5.6%, haematuria in 1.9%, perineal pain in 11.1%, and prostatorectal fistula in 0.9%. Erectile disfunction was found in 98.1%. Conclusions. Cryotherapy is an effective and minimally invasive treatment for primary PC in well-selected cases, with low surgical risk and good results in terms of BPFS, cancer-specific survival, and overall survival.

Cryotherapy for Primary Treatment of Prostate Cancer: Intermediate Term Results of a Prospective Study from a Single Institution

PubMed Central

Rodríguez, S. Alvarez; Arias Fúnez, F.; Bueno Bravo, C.; Rodríguez-Patrón Rodríguez, R.; Sanz Mayayo, E.; Palacios, V. Hevia; Burgos Revilla, F. J.

2014-01-01

Purpose. Published data about cryotherapy for prostate cancer (PC) treatment are based on case series with a lack of clinical trials and the inexistence of a validated definition of biochemical failure. A prospective study with standardized followup protocol was conducted in our institution. Material and Methods. Prospective study of a series of cases including 108 patients diagnosed with localized PC at clinical stage T1c-T2c treated by primary cryoablation and median followup of 61 months. Criteria of biochemical recurrence were unified according to the American Society for Therapeutic Radiology and Oncology (ASTRO). End points were biochemical progression-free survival (BPFS), cancer-specific survival, and overall survival. Rate of complications was reported. Results. The BPFS for low-, medium-, and high-risk patients was 96.4%, 91.2%, and 62.2%, respectively. Cancer-specific survival was 98.1%. Overall survival reached 94.4%. Complications included incontinence in 5.6%, urinary tract obstruction in 1.9%, urethral sloughing in 5.6%, haematuria in 1.9%, perineal pain in 11.1%, and prostatorectal fistula in 0.9%. Erectile disfunction was found in 98.1%. Conclusions. Cryotherapy is an effective and minimally invasive treatment for primary PC in well-selected cases, with low surgical risk and good results in terms of BPFS, cancer-specific survival, and overall survival. PMID:24693437

Alcohol consumption and prostate cancer: a mini review.

PubMed

Rizos, Ch; Papassava, M; Golias, Ch; Charalabopoulos, K

2010-07-01

Prostate cancer has become a major public health problem worldwide although the etiology of prostate cancer remains largely unknown. Dietary factors, dietary supplements, and physical activity might be important in the prevention of the disease. In the majority of studies published, it was observed that high consumption of meat, alcohol and dairy products has been linked to a greater risk. Specifically, alcohol use, and particularly heavy use, may cause cancers of liver, esophagus, larynx, pharynx and oral cavity, with risks for the aero-digestive cancers. Moderate use among women has been related with increases in breast cancer. Alcohol consumption is a modifiable lifestyle factor that may affect prostate cancer risk. Alcohol alters the hormonal environment and in parallel, containing chemical substances such as flavonoids (red wine), may alter tumor cell growth. In this mini review, the relation between alcohol consumption and prostate cancer risk is analyzed.

Interdisciplinary decision making in prostate cancer therapy – 5-years’ time trends at the Interdisciplinary Prostate Cancer Center (IPC) of the Charité Berlin

PubMed Central

2013-01-01

Background Patients with prostate cancer face the difficult decision between a wide range of therapeutic options. These men require elaborate information about their individual risk profile and the therapeutic strategies´ risks and benefits to choose the best possible option. In order to detect time trends and quality improvements between an early patient population (2003/2004) and a later reference group (2007/2008) data was analysed with regards to epidemiologic parameters, differences in diagnostics and the type and ranking of the recommended therapies taking into account changes to Gleason Grading System and implementation of new therapeutic strategies, particularly Active surveillance, in 2005. Methods Data from all 496 consecutive patients who received consultation in 2003/2004 (n = 280) and 2007/2008 (n = 216) was retrospectively evaluated. Categorical variables were compared using the Chi-square test. Dependent variables were analysed using the unpaired Students´ t-test and the Mann–Whitney U-test. Results The cohorts were comparable concerning clinical stage, initial PSA, prostate volume, comorbidities and organ confined disease. Patients in Cohort I were younger (66.44 vs. 69.31y; p < .001) and had a longer life expectancy (17.22 vs. 14.75y; p < .001). 50.9%, 28.2% and 20.9% in Cohort I and 37.2%, 39.6% and 23.2% in Cohort II showed low-, intermediate- and high-risk disease (D´Amico) with a trend towards an increased risk profile in Cohort II (p = .066). The risk-adapted therapy recommended as first option was radical prostatectomy for 91.5% in Cohort I and 69.7% in Cohort II, radiation therapy for 83.7% in Cohort I and 50.7% in Cohort II, and other therapies (brachytherapy, Active surveillance, Watchful waiting, high-intensity focused ultrasound) for 6.5% in Cohort I and 6.9% in Cohort II (p < .001). Radiation therapy was predominant in both cohorts as second treatment option (p < .001). Time trends showing quality improvement involved an increase in biopsy cores (9.95 ± 2.38 vs. 8.43 ± 2.29; p < .001) and an increased recommendation for bilateral nerve sparing (p < .001). Conclusion In the earlier years, younger patients with a more favourable risk profile presented for interdisciplinary consultation. A unilateral recommendation for radical prostatectomy and radiation therapy was predominant. In the later years, the patient population was considerably older. However, this group may have benefitted from optimised diagnostic possibilities and a wider range of treatment options. PMID:23915212

A Population-Based Study of Dietary Acrylamide and Prostate Cancer Risk

DTIC Science & Technology

2006-03-01

159 microgram/day. 3. The four food products that contributed the most to the total intake of acrylamide among controls were crisp bread, coffee ... Acrylamide and Prostate Cancer Risk PRINCIPLE INVESTIGATOR: Hans-Olov Adami, M.D., Ph.D. CONTRACTING ORGANIZATION: Karolinska...NUMBER A Population-Based Study of Dietary Acrylamide and Prostate Cancer Risk 5b. GRANT NUMBER W81XWH-04-1-0288 5c. PROGRAM ELEMENT NUMBER

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2012-11-01

randomized placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer...and that this risk differed between men who took finasteride versus those who took the placebo. The strongest association was seen for a cluster of 9...SNPs in NPAS2, which was associated with total prostate cancer risk in the finasteride group but not in the placebo group. The most significant NPAS2

Prostate-Specific Antigen at 4 to 5 Years After Low-Dose-Rate Prostate Brachytherapy Is a Strong Predictor of Disease-Free Survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lo, Andrea C.; Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia; Morris, W. James, E-mail: JMorris@bccancer.bc.ca

2014-01-01

Purpose: To determine (1) the prognostic utility of prostate-specific antigen (PSA) concentration at 45 to 60 months (48mPSA) after low-dose-rate prostate brachytherapy (LDR-PB); (2) the predictors of 48mPSA; and (3) the prognostic utility of directional trends between PSA levels at 24, 36, and 48 months after LDR-PB. Methods and Materials: Between 1998 and 2008, 2223 patients with low- and intermediate-risk prostate cancer received LDR-PB monotherapy. A cohort of 1434 of these patients was identified with a documented 48mPSA and no evidence of disease relapse prior to the 48mPSA. In addition, a subset of this cohort (n=585) was identified with ≥72more » months of follow-up and documented PSA values at both 24 and 36 months after implantation. Results: Median follow-up time was 76 months. Eight-year Kaplan-Meier disease-free survival (DFS) rates were 100% vs 73.4% for patients with 48mPSA ≤0.2 vs those with >0.2 ng/mL; 99.1% versus 53.8% for a 48mPSA threshold of ≤0.4 versus >0.4 ng/mL, respectively; and 97.3% versus 0% for a threshold of ≤1.0 versus >1.0 ng/mL, respectively. On multivariate analysis, the only factor predictive of DFS was 48mPSA (P<.0001). On subset analysis (n=585), 29 patients had a PSA rise (defined as >0.2 ng/mL) between 24 and 36 months, 24 patients had a rise between 36 and 48 months, and 11 patients had rises over both intervals. Failure rates in these patients were 52%, 79%, and 100%, respectively. On multivariate analysis, initial PSA, androgen deprivation therapy, and dose to 90% of the prostate significantly correlated with 48mPSA but together accounted for only ∼5% of its total variance. Conclusions: The 48mPSA after LDR-PB is highly predictive of long-term DFS. Patients with 48mPSA ≤0.4 ng/mL had a <1% risk of disease relapse at 8 years, whereas all patients with 48mPSA >1.0 ng/mL relapsed. Consecutive PSA rises of >0.2 ng/mL from 24 to 36 months and from 36 to 48 months were also highly predictive of subsequent failure.« less

Prostate-specific antigen testing in inner London general practices: are those at higher risk most likely to get tested?

PubMed

Nderitu, Paul; Van Hemelrijck, Mieke; Ashworth, Mark; Mathur, Rohini; Hull, Sally; Dudek, Alexandra; Chowdhury, Simon

2016-07-12

To investigate the association between factors influencing prostate-specific antigen (PSA) testing prevalence including prostate cancer risk factors (age, ethnicity, obesity) and non-risk factors (social deprivation and comorbidity). A cross-sectional database of 136 inner London general practices from 1 August 2009 to 31 July 2014. Men aged ≥40 years without prostate cancer were included (n=150 481). Logistic regression analyses were used to estimate the association between PSA testing and age, ethnicity, social deprivation, body mass index (BMI) and comorbidity while adjusting for age, benign prostatic hypertrophy, prostatitis and tamsulosin or finasteride use. PSA testing prevalence was 8.2% (2013-2014), and the mean age was 54 years (SD 11). PSA testing was positively associated with age (OR 70-74 years compared to 40-44 years: 7.34 (95% CI 6.82 to 7.90)), ethnicity (black) (OR compared to white: 1.78 (95% CI 1.71 to 1.85)), increasing BMI and cardiovascular comorbidity. Testing was negatively associated with Chinese ethnicity and with increasing social deprivation. PSA testing among black patients was higher compared to that among white patients, which differs from lower testing rates seen in previous studies. PSA testing was positively associated with prostate cancer risk factors and non-risk factors. Association with non-risk factors may increase the risk of unnecessary invasive diagnostic procedures. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Prostate cancer chemoprevention agent development: the National Cancer Institute, Division of Cancer Prevention portfolio.

PubMed

Parnes, Howard L; House, Margaret G; Kagan, Jacob; Kausal, David J; Lieberman, Ronald

2004-02-01

We describe the current National Cancer Institute chemoprevention agent development program and provide a summary of the intermediate end points used. The National Cancer Institute is currently sponsoring a wide range of studies of promising chemoprevention agents in a variety of informative cohorts, eg high grade prostatic intraepithelial neoplasia, positive family history of cancer, increased prostate specific antigen with negative biopsies, prostate cancer followed expectantly, prostate cancer awaiting definitive therapy and the general population. The rationale for each agent under investigation is derived from epidemiological observations, prostate cancer treatment trials, secondary analyses of large cancer prevention studies, an understanding of cancer biology and prostate carcinogenesis, and/or experimental animal models. Carcinogenesis is a multistep process occurring over decades which is characterized by disruption of the normal regulatory pathways controlling cellular proliferation, programmed cell death and differentiation. Administration of agents to reverse, inhibit or slow this process of malignant transformation is known as chemoprevention. Chemoprevention represents a promising approach to reducing the morbidity and mortality of prostate cancer. A variety of agents are currently being studied in phase 2 clinical trials, some of which may warrant subsequent evaluation in phase 3 trials with definitive cancer end points. Two large phase 3 trials, the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, which are ongoing, are also sponsored by the National Cancer Institute.

Case–control and prospective studies of dietary α-linolenic acid intake and prostate cancer risk: a meta-analysis

PubMed Central

Carleton, Amanda J; Sievenpiper, John L; de Souza, Russell; McKeown-Eyssen, Gail; Jenkins, David J A

2013-01-01

Objective α-Linolenic acid (ALA) is considered to be a cardioprotective nutrient; however, some epidemiological studies have suggested that dietary ALA intake increases the risk of prostate cancer. The main objective was to conduct a systematic review and meta-analysis of case–control and prospective studies investigating the association between dietary ALA intake and prostate cancer risk. Design A systematic review and meta-analysis were conducted by searching MEDLINE and EMBASE for relevant prospective and case–control studies. Included studies We included all prospective cohort, case–control, nested case-cohort and nested case–control studies that investigated the effect of dietary ALA intake on the incidence (or diagnosis) of prostate cancer and provided relative risk (RR), HR or OR estimates. Primary outcome measure Data were pooled using the generic inverse variance method with a random effects model from studies that compared the highest ALA quantile with the lowest ALA quantile. Risk estimates were expressed as RR with 95% CIs. Heterogeneity was assessed by χ2 and quantified by I2. Results Data from five prospective and seven case–control studies were pooled. The overall RR estimate showed ALA intake to be positively but non-significantly associated with prostate cancer risk (1.08 (0.90 to 1.29), p=0.40; I2=85%), but the interpretation was complicated by evidence of heterogeneity not explained by study design. A weak, non-significant protective effect of ALA intake on prostate cancer risk in the prospective studies became significant (0.91 (0.83 to 0.99), p=0.02) without evidence of heterogeneity (I2=8%, p=0.35) on removal of one study during sensitivity analyses. Conclusions This analysis failed to confirm an association between dietary ALA intake and prostate cancer risk. Larger and longer observational and interventional studies are needed to define the role of ALA and prostate cancer. PMID:23674441

Risk and presenting features of prostate cancer amongst African-Caribbean, South Asian and European men in North-east London.

PubMed

Chinegwundoh, Frank; Enver, Mohamed; Lee, Angela; Nargund, Vinod; Oliver, Tim; Ben-Shlomo, Yoav

2006-12-01

To determine whether there are ethnic differences in the incidence and presenting features of all patients with prostate cancer presenting in North-east London, UK. All newly diagnosed men with prostate cancer between 1999 and 2000 who were resident in the East London and City Health Authority were identified from various sources. Key clinical features were extracted from hospital records. The age-adjusted incidence rates for European, South Asian and African-Caribbean patients were calculated using census denominator data. For men aged >50 years the annual age-adjusted incidence rates (95% confidence interval) were 213 (186-240), 647 (504-789) and 199 (85-310) for the European, African-Caribbean and South Asian patients, respectively. African-Caribbean men had a three times greater risk (risk ratio 3.07, 2.40-3.93, P < 0.001) than European men. South Asian men had a lower risk of prostate cancer but this could have been compatible with chance. There was no evidence of marked ethnic differences for prostate-specific antigen levels, clinical staging and Gleason scores. The greater risk of prostate cancer for African-Caribbean men in South-east England is consistent with data from the USA and the Caribbean. Future work needs to determine whether this risk differs according to country of origin, and which genetic and/or environmental risk factors might be important in explaining these observations.

Mediterranean Dietary Pattern is Associated with Low Risk of Aggressive Prostate Cancer: MCC-Spain Study.

PubMed

Castelló, Adela; Boldo, Elena; Amiano, Pilar; Castaño-Vinyals, Gemma; Aragonés, Nuria; Gómez-Acebo, Inés; Peiró, Rosana; Jimenez-Moleón, Jose Juan; Alguacil, Juan; Tardón, Adonina; Cecchini, Lluís; Lope, Virginia; Dierssen-Sotos, Trinidad; Mengual, Lourdes; Kogevinas, Manolis; Pollán, Marina; Pérez-Gómez, Beatriz

2018-02-01

We explored the association of the previously described Western, prudent and Mediterranean dietary patterns with prostate cancer risk by tumor aggressiveness and extension. MCC-Spain (Multicase-Control Study on Common Tumors in Spain) is a population based, multicase-control study that was done in 7 Spanish provinces between September 2008 and December 2013. It collected anthropometric, epidemiological and dietary information on 754 histologically confirmed incident cases of prostate cancer and 1,277 controls 38 to 85 years old. Three previously identified dietary patterns, including Western, prudent and Mediterranean, were reconstructed using MCC-Spain data. The association of each pattern with prostate cancer risk was assessed by logistic regression models with random, province specific intercepts. Risk according to tumor aggressiveness (Gleason score 6 vs greater than 6) and extension (cT1-cT2a vs cT2b-cT4) was evaluated by multinomial regression models. High adherence to a Mediterranean dietary pattern rich not only in fruits and vegetables but also in fish, legumes and olive oil was specifically associated with a lower risk of Gleason score greater than 6 prostate cancer (quartile 3 vs 1 relative RR 0.66, 95% CI 0.46-0.96 and quartile 4 vs 1 relative RR 0.68, 95% CI 0.46-1.01, p-trend = 0.023) or with higher clinical stage (cT2b-T4 quartile 4 vs 1 relative RR 0.49, 95% CI 0.25-0.96, p-trend = 0.024). This association was not observed with the prudent pattern, which combines vegetables and fruits with low fat dairy products, whole grains and juices. The Western pattern did not show any association with prostate cancer risk. Nutritional recommendations for prostate cancer prevention should consider whole dietary patterns instead of individual foods. We found important differences between the Mediterranean dietary pattern, which was associated with a lower risk of aggressive prostate cancer, and Western and prudent dietary patterns, which had no relationship with prostate cancer risk. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

PubMed Central

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Aim Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients and methods Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3–6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. Results In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. Conclusion There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. PMID:27274277

Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

PubMed

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3-6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered.

Automatic segmentation of male pelvic anatomy on computed tomography images: a comparison with multiple observers in the context of a multicentre clinical trial.

PubMed

Geraghty, John P; Grogan, Garry; Ebert, Martin A

2013-04-30

This study investigates the variation in segmentation of several pelvic anatomical structures on computed tomography (CT) between multiple observers and a commercial automatic segmentation method, in the context of quality assurance and evaluation during a multicentre clinical trial. CT scans of two prostate cancer patients ('benchmarking cases'), one high risk (HR) and one intermediate risk (IR), were sent to multiple radiotherapy centres for segmentation of prostate, rectum and bladder structures according to the TROG 03.04 "RADAR" trial protocol definitions. The same structures were automatically segmented using iPlan software for the same two patients, allowing structures defined by automatic segmentation to be quantitatively compared with those defined by multiple observers. A sample of twenty trial patient datasets were also used to automatically generate anatomical structures for quantitative comparison with structures defined by individual observers for the same datasets. There was considerable agreement amongst all observers and automatic segmentation of the benchmarking cases for bladder (mean spatial variations < 0.4 cm across the majority of image slices). Although there was some variation in interpretation of the superior-inferior (cranio-caudal) extent of rectum, human-observer contours were typically within a mean 0.6 cm of automatically-defined contours. Prostate structures were more consistent for the HR case than the IR case with all human observers segmenting a prostate with considerably more volume (mean +113.3%) than that automatically segmented. Similar results were seen across the twenty sample datasets, with disagreement between iPlan and observers dominant at the prostatic apex and superior part of the rectum, which is consistent with observations made during quality assurance reviews during the trial. This study has demonstrated quantitative analysis for comparison of multi-observer segmentation studies. For automatic segmentation algorithms based on image-registration as in iPlan, it is apparent that agreement between observer and automatic segmentation will be a function of patient-specific image characteristics, particularly for anatomy with poor contrast definition. For this reason, it is suggested that automatic registration based on transformation of a single reference dataset adds a significant systematic bias to the resulting volumes and their use in the context of a multicentre trial should be carefully considered.

Expression differences of circulating microRNAs in metastatic castration resistant prostate cancer and low-risk, localized prostate cancer.

PubMed

Nguyen, Han Christine Ngoc; Xie, Wanling; Yang, Ming; Hsieh, Chen-Lin; Drouin, Sarah; Lee, Gwo-Shu Mary; Kantoff, Philip W

2013-03-01

Recent studies show that microRNAs (miRNAs), small non-coding RNAs that negatively regulate gene expression, may have potential for monitoring cancer status. We investigated circulating miRNAs in prostate cancer that may be associated with the progression of hormone-sensitive primary tumors to metastatic castration resistant prostate cancer (CRPC) after androgen deprivation therapy. Using genome-wide expression profiling by TaqMan Human MicroRNA Arrays (Applied Biosystems) and/or quantitative real-time polymerase chain reaction, we compared the expression levels of miRNAs in serum samples from 28 patients of low-risk localized disease, 30 of high-risk localized disease and 26 of metastatic CRPC. We demonstrated that serum samples from patients of low risk, localized prostate cancer and metastatic CRPC patients exhibit distinct circulating miRNA signatures. MiR-375, miR-378*, and miR-141 were significantly over-expressed in serum from CRPC patients compared with serum from low-risk localized patients, while miR-409-3p was significantly under-expressed. In prostate primary tumor samples, miR-375 and miR-141 also had significantly higher expression levels compared with those in normal prostate tissue. Circulating miRNAs, particularly miR-375, miR-141, miR-378*, and miR-409-3p, are differentially expressed in serum samples from prostate cancer patients. In the search for improved minimally invasive methods to follow cancer pathogenesis, the correlation of disease status with the expression patterns of circulating miRNAs may indicate the potential importance of circulating miRNAs as prognostic markers for prostate cancer progression. Copyright © 2012 Wiley Periodicals, Inc.

A meta-analysis of individual participant data reveals an association between circulating levels of IGF-I and prostate cancer risk

PubMed Central

Travis, Ruth C.; Appleby, Paul N.; Martin, Richard M.; Holly, Jeff M.P.; Albanes, Demetrius; Black, Amanda; Bueno-de-Mesquita, H.B(as).; Chan, June M.; Chen, Chu; Chirlaque, Maria-Dolores; Cook, Michael B.; Deschasaux, Mélanie; Donovan, Jenny L.; Ferrucci, Luigi; Galan, Pilar; Giles, Graham G.; Giovannucci, Edward L.; Gunter, Marc J.; Habel, Laurel A.; Hamdy, Freddie C.; Helzlsouer, Kathy J.; Hercberg, Serge; Hoover, Robert N.; Janssen, Joseph A.M.J.L.; Kaaks, Rudolf; Kubo, Tatsuhiko; Le Marchand, Loic; Metter, E. Jeffrey; Mikami, Kazuya; Morris, Joan K.; Neal, David E.; Neuhouser, Marian L.; Ozasa, Kotaro; Palli, Domenico; Platz, Elizabeth A.; Pollak, Michael; Price, Alison J.; Roobol, Monique J.; Schaefer, Catherine; Schenk, Jeannette M.; Severi, Gianluca; Stampfer, Meir J.; Stattin, Pär; Tamakoshi, Akiko; Tangen, Catherine M.; Touvier, Mathilde; Wald, Nicholas J.; Weiss, Noel S.; Ziegler, Regina G.

2016-01-01

The role of insulin-like growth factors (IGFs) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the odds ratios (ORs) for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was weakly inversely associated with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval=1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. PMID:26921328

Linac based SBRT for prostate cancer in 5 fractions with VMAT and flattening filter free beams: preliminary report of a phase II study.

PubMed

Alongi, Filippo; Cozzi, Luca; Arcangeli, Stefano; Iftode, Cristina; Comito, Tiziana; Villa, Elisa; Lobefalo, Francesca; Navarria, Pierina; Reggiori, Giacomo; Mancosu, Pietro; Clerici, Elena; Fogliata, Antonella; Tomatis, Stefano; Taverna, Gianluigi; Graziotti, Pierpaolo; Scorsetti, Marta

2013-07-08

To evaluate the feasibility and early side effects of a short course hypo-fractionated SBRT programme with Volumetric Modulated Arc Therapy (VMAT) and Flattening Filter Free (FFF) beams. A prospective phase I-II study, started on February 2012. Inclusion criteria were: age ≤ 80 years, WHO-PS ≤ 2, PSA ≤ 20 ng/ml, histologically proven prostate adenocarcinoma, T1-T2 stage, no distant metastases, no previous surgery other than TURP, no malignant tumours in the previous 5 years, IPSS 0-7. The schedule was 35 Gy in 5 alternative days. SBRT was delivered with RapidArc VMAT, with 10MV FFF photons. Toxicity assessment was performed according to CTCAE v4.0 scale. EPIC questionnaires assessed Quality-of-Life. Neo-adjuvant/concomitant hormonal-therapy was prescribed according to risk classification. SpaceOAR™ gel was optionally implanted to increase the separation space between the prostate and the rectal wall. Median follow-up was 11 months (range: 5-16); 40 patients were recruited in the protocol and treated. According to NCCN criteria, 26/40 patients were low-risk and 14/40 were intermediate risk. Median age was 70 years (56-80), median initial PSA was 6.25 ng/ml (0.50-13.43 ng/ml). Median Gleason score was 6 (6-7). All patients completed the treatment as programmed (median 11.8 days (9-22). Acute Toxicities were as follow: Rectum G0: 30/40 cases (75%); G1: 6/40 (15%); G2: 4/40 (10%). Genito-urinary: G0: 16/40 (40%); G1: 8/40 (20%); G2: 16/34 (40%). In two G2 urinary retention cases, intermittent catheter was needed. No acute G3 or greater toxicity was found. Median treatment time was 126 sec (120-136). SpaceOAR™ was implanted in 8 patients. PSA reduction from the pre-treatment value of the marker was documented in all patients. Early findings suggest that SBRT with RapidArc and FFF beams for prostate cancer in 5 fractions is feasible and tolerated in acute setting. Longer follow-up is needed for assessment of late toxicity and outcome.

Effects of radiation on the incidence of prostate cancer among Nagasaki atomic bomb survivors.

PubMed

Kondo, Hisayoshi; Soda, Midori; Mine, Mariko; Yokota, Kenichi

2013-10-01

Atomic bomb survivors have been reported to have an increased risk of some cancers, especially leukemia. However, the risk of prostate cancer in atomic bomb survivors is not known to have been examined previously. This study examined the association between atomic bomb radiation and the incidence of prostate cancer among male Nagasaki atomic bomb survivors. The subjects were classified by distance from the hypocenter into a proximal group (<2 km), a distal group (≥2 km), and an early entrance group (those who entered the region <2 km from the hypocenter within 2 weeks after the explosion). Between 1996 and 2009, 631 new cases of prostate cancer were identified among approximately 18 400 male Nagasaki atomic bomb survivors who were alive in 1996. The Cox proportional hazard model was used to estimate the risk of prostate cancer development, with adjustment for age at atomic bomb explosion, attained age, smoking status, and alcohol consumption. Compared with the distal group, the proximal group had significant increased risks of total, localized, and high-grade prostate cancer (relative risk and 95% confidence interval: 1.51 [1.21-1.89]; 1.80 [1.26-2.57]; and 1.88 [1.20-2.94], respectively). This report is the first known to reveal a significant relationship between atomic bomb radiation and prostate cancer. © 2013 Japanese Cancer Association.

Circulating Selenium and Prostate Cancer Risk: A Mendelian Randomization Analysis.

PubMed

Yarmolinsky, James; Bonilla, Carolina; Haycock, Philip C; Langdon, Ryan J Q; Lotta, Luca A; Langenberg, Claudia; Relton, Caroline L; Lewis, Sarah J; Evans, David M; Davey Smith, George; Martin, Richard M

2018-05-17

In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenium supplementation (causing a median 114 μg/L increase in circulating selenium) did not lower overall prostate cancer risk, but increased risk of high-grade prostate cancer and type 2 diabetes. Mendelian randomization analysis uses genetic variants to proxy modifiable risk factors and can strengthen causal inference in observational studies. We constructed a genetic instrument comprising 11 single nucleotide polymorphisms robustly (P < 5 × 10-8) associated with circulating selenium in genome-wide association studies. In a Mendelian randomization analysis of 72 729 men in the PRACTICAL Consortium (44 825 case subjects, 27 904 control subjects), 114 μg/L higher genetically elevated circulating selenium was not associated with prostate cancer (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 0.89 to 1.13). In concordance with findings from SELECT, selenium was weakly associated with advanced (including high-grade) prostate cancer (OR = 1.21, 95% CI = 0.98 to 1.49) and type 2 diabetes (OR = 1.18, 95% CI = 0.97 to 1.43; in a type 2 diabetes genome-wide association study meta-analysis with up to 49 266 case subjects and 249 906 control subjects). Our Mendelian randomization analyses do not support a role for selenium supplementation in prostate cancer prevention and suggest that supplementation could have adverse effects on risks of advanced prostate cancer and type 2 diabetes.

Circumcision and prostate cancer: a population-based case-control study in Montréal, Canada

PubMed Central

Spence, Andrea R; Rousseau, Marie-Claude; Karakiewicz, Pierre I; Parent, Marie-Élise

2014-01-01

Objectives To investigate the possible association between circumcision and prostate cancer risk, to examine whether age at circumcision influences prostate cancer risk, and to determine whether race modifies the circumcision–prostate cancer relationship. Subjects and Methods PROtEuS (Prostate Cancer and Environment Study), a population-based case-control study set amongst the mainly French-speaking population in Montréal, Canada, was used to address study objectives. The study included 1590 pathologically confirmed prostate cancer cases diagnosed in a Montréal French hospital between 2005 and 2009, and 1618 population controls ascertained from the French electoral list, frequency-matched to cases by age. In-person interviews elicited information on sociodemographic, lifestyle and environmental factors. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between circumcision, age at circumcision and prostate cancer risk, adjusting for age, ancestry, family history of prostate cancer, prostate cancer screening history, education, and history of sexually transmitted infections. Results Circumcised men had a slightly lower risk, albeit not statistically significant, of developing prostate cancer than uncircumcised men (OR 0.89, 95% CI 0.76–1.04). Circumcision was found to be protective in men circumcised aged ≥36 years (OR 0.55, 95% CI 0.30–0.98). A weaker protective effect was seen among men circumcised within 1 year of birth (OR 0.86, 95% CI 0.72–1.04). The strongest protective effect of circumcision was recorded in Black men (OR 0.40, 95% CI 0.19–0.86, P-value for interaction 0.02) but no association was found with other ancestral groups. Conclusion Our findings provide novel evidence for a protective effect of circumcision against prostate cancer development, especially in those circumcised aged ≥36 years; although circumcision before the age of 1 year may also confer protection. Circumcision appeared to be protective only among Black men, a group that has the highest rate of disease. Further research into the differences in effect of circumcision on prostate cancer risk by ancestry is warranted, as is the influence of age at circumcision. PMID:24655933

Lifestyle and Risk of Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Cohort of United States Male Health Professionals.

PubMed

Zhang, Ran; Sutcliffe, Siobhan; Giovannucci, Edward; Willett, Walter C; Platz, Elizabeth A; Rosner, Bernard A; Dimitrakoff, Jordan D; Wu, Kana

2015-11-01

Although chronic prostatitis/chronic pelvic pain syndrome is a prevalent urological disorder among men of all ages, its etiology remains unknown. Only a few previous studies have examined associations between lifestyle factors and chronic prostatitis/chronic pelvic pain syndrome, of which most were limited by the cross-sectional study design and lack of control for possible confounders. To address these limitations we performed a cohort study of major lifestyle factors (obesity, smoking and hypertension) and chronic prostatitis/chronic pelvic pain syndrome risk in the HPFS (Health Professionals Follow-up Study), a large ongoing cohort of United States based male health professionals. The HPFS includes 51,529 men who were 40 to 75 years old at baseline in 1986. At enrollment and every 2 years thereafter participants have completed questionnaires on lifestyle and health conditions. In 2008 participants completed an additional set of questions on recent chronic prostatitis/chronic pelvic pain syndrome pain symptoms modified from the NIH (National Institutes of Health)-CPSI (Chronic Prostatitis Symptom Index) as well as questions on approximate date of symptom onset. The 653 participants with NIH-CPSI pain scores 8 or greater who first experienced symptoms after 1986 were considered incident chronic prostatitis/chronic pelvic pain syndrome cases and the 19,138 who completed chronic prostatitis/chronic pelvic pain syndrome questions but did not report chronic prostatitis/chronic pelvic pain syndrome related pain were considered noncases. No associations were observed for baseline body mass index, waist circumference, waist-to-hip ratio, cigarette smoking and hypertension with chronic prostatitis/chronic pelvic pain syndrome risk (each OR ≤1.34). In this large cohort study none of the lifestyle factors examined was associated with chronic prostatitis/chronic pelvic pain syndrome risk. As the etiology of chronic prostatitis/chronic pelvic pain syndrome remains unknown, additional prospective studies are needed to elucidate modifiable risk factors for this common condition. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

An epidemiological analysis of potential associations between C-reactive protein, inflammation, and prostate cancer in the male US population using the 2009 - 2010 National Health and Nutrition Examination Survey (NHANES) data

NASA Astrophysics Data System (ADS)

St. Hill, Catherine; Lutfiyya, M. Nawal

2015-08-01

Prostate cancer is the second leading cause of cancer-related deaths in US males, yet much remains to be learned about the role of inflammation in its etiology. We hypothesized that preexisting exposure to chronic inflammatory conditions caused by infectious agents or inflammatory diseases increase the risk of prostate cancer. Using the 2009-2010 National Health and Nutrition Examination Survey, we examined the relationships between demographic variables, inflammation, infection, circulating plasma C-reactive protein (CRP), and the risk of occurrence of prostate cancer in US men over 18 years of age. Using IBM SPSS, we performed bivariate and logistic regression analyses using high CRP values as the dependent variable and five study covariates including prostate cancer status. From 2009 - 2010, an estimated 5,448,373 men reported having prostate cancer of which the majority were Caucasian (70.1%) and were aged 40 years and older (62.7%). Bivariate analyses demonstrated that high CRP was not associated with an increased risk of prostate cancer. Greater odds of having prostate cancer were revealed for men that had inflammation related to disease (OR = 1.029, CI 1.029-1.029) and those who were not taking drugs to control inflammation (OR = 1.330, CI 1.324-1.336). Men who did not have inflammation resulting from non-infectious diseases had greater odds of not having prostate cancer (OR = 1.031, CI 1.030-1.031). Logistic regression analysis yielded that men with the highest CRP values had greater odds of having higher household incomes and lower odds of having received higher education, being aged 40 years or older, being of a race or ethnicity different from other, and of having prostate cancer. Our results show that chronic inflammation of multiple etiologies is a risk factor for prostate cancer and that CRP is not associated with this increased risk. Further research is needed to elucidate the complex interactions between inflammation and prostate cancer.

Patterns of Recurrence After Low-Dose-Rate Prostate Brachytherapy: A Population-Based Study of 2223 Consecutive Low- and Intermediate-Risk Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lo, Andrea C.; Morris, W. James, E-mail: JMorris@bccancer.bc.ca; Pickles, Tom

Objectives: This study examined patterns of recurrence after low–dose-rate prostate brachytherapy (LDR-PB), estimated local recurrence rate and compared that rate to the estimated local recurrence rate after radical prostatectomy (RP). Methods and Materials: A prospective database was maintained with clinical, dosimetric, and outcome data for all LDR-PB implantation procedures performed at our institution. From 1998 to 2008, 2223 patients with prostate cancer received LDR-PB without supplemental external beam radiation therapy. Patients who developed Phoenix-defined biochemical failure were reviewed for sites of relapse and investigations completed. Results: At a median follow-up of 5 years, 108 of 2223 patients (4.8%) developed biochemical relapse.more » In 1 additional patient, local relapse was found on transurethral prostate resection, but his prostate-specific antigen concentration was well short of triggering Phoenix-defined failure. Of the 109 patients with disease relapse, 18 of 2223 (0.8%) had a proven local recurrence, and 30 of 2223 (1.3%) had a proven distant recurrence. The remaining 61 of 2223 patients (2.7%) had unidentified sites of recurrence; of these, 57 patients (93%) had digital rectal examinations (DREs), 18 (30%) had post-treatment biopsies, 45 (74%) had bone scans, and 34 (56%) had computed tomography imaging of the abdomen and pelvis. If every biochemical failure were local, the local recurrence rate would be as high as 4.9%; however, by excluding those with proven distant failure and those with both a negative DRE and biopsy, we estimate that the local recurrence rate is 2.7% or less. Conclusions: In the context of limitations of the study design, our population-based analysis indicates that the local recurrence rate after LDR-PB is as low or lower than that after RP in our jurisdiction.« less

Impact of region contouring variability on image-based focal therapy evaluation

NASA Astrophysics Data System (ADS)

Gibson, Eli; Donaldson, Ian A.; Shah, Taimur T.; Hu, Yipeng; Ahmed, Hashim U.; Barratt, Dean C.

2016-03-01

Motivation: Focal therapy is an emerging low-morbidity treatment option for low-intermediate risk prostate cancer; however, challenges remain in accurately delivering treatment to specified targets and determining treatment success. Registered multi-parametric magnetic resonance imaging (MPMRI) acquired before and after treatment can support focal therapy evaluation and optimization; however, contouring variability, when defining the prostate, the clinical target volume (CTV) and the ablation region in images, reduces the precision of quantitative image-based focal therapy evaluation metrics. To inform the interpretation and clarify the limitations of such metrics, we investigated inter-observer contouring variability and its impact on four metrics. Methods: Pre-therapy and 2-week-post-therapy standard-of-care MPMRI were acquired from 5 focal cryotherapy patients. Two clinicians independently contoured, on each slice, the prostate (pre- and post-treatment) and the dominant index lesion CTV (pre-treatment) in the T2-weighted MRI, and the ablated region (post-treatment) in the dynamic-contrast- enhanced MRI. For each combination of clinician contours, post-treatment images were registered to pre-treatment images using a 3D biomechanical-model-based registration of prostate surfaces, and four metrics were computed: the proportion of the target tissue region that was ablated and the target:ablated region volume ratio for each of two targets (the CTV and an expanded planning target volume). Variance components analysis was used to measure the contribution of each type of contour to the variance in the therapy evaluation metrics. Conclusions: 14-23% of evaluation metric variance was attributable to contouring variability (including 6-12% from ablation region contouring); reducing this variability could improve the precision of focal therapy evaluation metrics.

Clinical and technical feasibility of ultra-boost irradiation in Dominant Intraprostatic Lesion by Tomotherapy: preliminary experience and revision of literature.

PubMed

Garibaldi, Elisabetta; Delmastro, Elena; Gabriele, Domenico; Bresciani, Sara; Russo, Filippo; Di Dia, Amalia; Cattari, Gaetano; Belli, Gabriella; Gabriele, Pietro

2016-03-01

The aim of this paper was to present our experience of dominant intraprostatic lesions (DIL) irradiation up to an EQD2 of 93,2 Gy with helical tomotherapy. Between March 2012 and December 2014, 15 staged II-III patients with intermediate-high risk prostate cancer were enrolled in our protocol of DIL dose escalation by Tomotherapy. All patients were submitted to a multiparametric MRI (including DCE and DWI series), in order to visualize DILs. Considering a mean α/β ratio of 3 for prostate cancer the prescribed doses were: 83.2 Gy in 32 fractions of 2.6 per fraction (EQD2=93.2 Gy) on the DILs, 75.2 Gy in 32 fractions of 2.35 Gy per fraction (EQD2=80.5 Gy) on the prostate gland and 67.2 Gy in 32 fraction of 2.1 (EQD2=68.5 Gy) on the seminal vesicles. With a mean follow-up of 16 months (range 2-39), no overall severe acute toxicities >G3 were observed; one patient out of 15 (6.6%) had acute gastrointestinal (GI) toxicity equal to G2, while two cases (13.3%) had G2 acute genitourinary (GU) toxicity. No >G2 late toxicity was observed. At last follow-up, for all patients, the biochemical disease free survival was 100%. The irradiation of the whole prostate and seminal vesicles up to an EQD2 of 80.5 Gy and of DILs up to 93.2 Gy was clinically feasible and safe, without acute severe toxicity. Although with a short follow-up, late toxicities are currently absent and no patient relapsed.

Prostate cancer: predicting high-risk prostate cancer-a novel stratification tool.

PubMed

Buck, Jessica; Chughtai, Bilal

2014-05-01

Currently, numerous systems exist for the identification of high-risk prostate cancer, but few of these systems can guide treatment strategies. A new stratification tool that uses common diagnostic factors can help to predict outcomes after radical prostatectomy. The tool aids physicians in the identification of appropriate candidates for aggressive, local treatment.

A study based on whole-genome sequencing yields a rare variant at 8q24 associated with prostate cancer

PubMed Central

Gudmundsson, Julius; Sulem, Patrick; Gudbjartsson, Daniel F.; Masson, Gisli; Agnarsson, Bjarni A.; Benediktsdottir, Kristrun R.; Sigurdsson, Asgeir; Magnusson, Olafur Th.; Gudjonsson, Sigurjon A.; Magnusdottir, Droplaug N.; Johannsdottir, Hrefna; Helgadottir, Hafdis Th.; Stacey, Simon N.; Jonasdottir, Adalbjorg; Olafsdottir, Stefania B.; Thorleifsson, Gudmar; Jonasson, Jon G.; Tryggvadottir, Laufey; Navarrete, Sebastian; Fuertes, Fernando; Helfand, Brian T.; Hu, Qiaoyan; Csiki, Irma E.; Mates, Ioan N.; Jinga, Viorel; Aben, Katja K. H.; van Oort, Inge M.; Vermeulen, Sita H.; Donovan, Jenny L.; Hamdy, Freddy C.; Ng, Chi-Fai; Chiu, Peter K.F.; Lau, Kin-Mang; Ng, Maggie C.Y.; Gulcher, Jeffrey R.; Kong, Augustine; Catalona, William J.; Mayordomo, Jose I.; Einarsson, Gudmundur V.; Barkardottir, Rosa B.; Jonsson, Eirikur; Mates, Dana; Neal, David E.; Kiemeney, Lambertus A.; Thorsteinsdottir, Unnur; Rafnar, Thorunn; Stefansson, Kari

2013-01-01

Western countries, prostate cancer is the most prevalent cancer of men, and one of the leading causes of cancer-related death in men. Several genome-wide association studies have yielded numerous common variants conferring risk of prostate cancer. In the present study we analyzed 32.5 million variants discovered by whole-genome sequencing 1,795 Icelanders. One variant was found to be associated with prostate cancer in European populations: rs188140481[A] (OR = 2.90, Pcomb = 6.2×10−34) located on 8q24, with an average risk allele control frequency of 0.54%. This variant is only very weakly correlated (r2 ≤ 0.06) with previously reported risk variants on 8q24, and remains significant after adjustment for all of them. Carriers of rs188140481[A] were diagnosed with prostate cancer 1.26 years younger than non-carriers (P = 0.0059). We also report results for the previously described HOXB13 mutation (rs138213197[T]), confirming it as prostate cancer risk variant in populations from all over Europe. PMID:23104005