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Sample records for clinically localized prostate

  1. Localized Prostate Cancer

    MedlinePlus

    ... a decision aid for men with clinically localized prostate cancer (available at http://effectivehealthcare.ahrq.gov/prostate_da) ... A Decision Aid for Men With Clinically Localized Prostate Cancer Page 1 of 24 Introduction Men with clinically ...

  2. Serum Testosterone Kinetics After Brachytherapy for Clinically Localized Prostate Cancer

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Lief, Jonathan H.; Allen, Zachariah A.; Wallner, Kent E.

    2012-01-01

    Purpose: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment. Methods and Materials: Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an association between testosterone changes and treatment outcomes or the occurrence of a PSA spike. Results: There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase {>=}25%, 23% of men experienced a decrease {>=}25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p < 0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21). Conclusion: Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA response

  3. Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer.

    PubMed

    Cha, Eugene K; Eastham, James A

    2015-05-01

    Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points. Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation.

  4. Stereotactic Body Radiotherapy for Localized Prostate Cancer: Interim Results of a Prospective Phase II Clinical Trial

    SciTech Connect

    King, Christopher R. Brooks, James D.; Gill, Harcharan; Pawlicki, Todd; Cotrutz, Cristian; Presti, Joseph C.

    2009-03-15

    Purpose: The radiobiology of prostate cancer favors a hypofractionated dose regimen. We report results of a prospective Phase II clinical trial of stereotactic body radiotherapy (SBRT) for localized prostate cancer. Methods and Materials: Forty-one low-risk prostate cancer patients with 6 months' minimum follow-up received 36.25 Gy in five fractions of 7.25 Gy with image-guided SBRT alone using the CyberKnife. The early (<3 months) and late (>6 months) urinary and rectal toxicities were assessed using validated quality of life questionnaires (International Prostate Symptom Score, Expanded Prostate Cancer Index Composite) and the Radiation Therapy Oncology Group (RTOG) toxicity criteria. Patterns of prostate-specific antigen (PSA) response are analyzed. Results: The median follow-up was 33 months. There were no RTOG Grade 4 acute or late rectal/urinary complications. There were 2 patients with RTOG Grade 3 late urinary toxicity and none with RTOG Grade 3 rectal complications. A reduced rate of severe rectal toxicities was observed with every-other-day vs. 5 consecutive days treatment regimen (0% vs. 38%, p = 0.0035). A benign PSA bounce (median, 0.4 ng/mL) was observed in 12 patients (29%) occurring at 18 months (median) after treatment. At last follow-up, no patient has had a PSA failure regardless of biochemical failure definition. Of 32 patients with 12 months minimum follow-up, 25 patients (78%) achieved a PSA nadir {<=}0.4 ng/mL. A PSA decline to progressively lower nadirs up to 3 years after treatment was observed. Conclusions: The early and late toxicity profile and PSA response for prostate SBRT are highly encouraging. Continued accrual and follow-up will be necessary to confirm durable biochemical control rates and low toxicity profiles.

  5. External Beam Radiotherapy for Clinically Localized Hormone-Refractory Prostate Cancer: Clinical Significance of Nadir Prostate-Specific Antigen Value Within 12 Months

    SciTech Connect

    Ogawa, Kazuhiko Nakamura, Katsumasa; Sasaki, Tomonari; Onishi, Hiroshi; Koizumi, Masahiko; Shioyama, Yoshiyuki; Araya, Masayuki; Mukumoto, Nobutaka M.S.; Mitsumori, Michihide; Teshima, Teruki

    2009-07-01

    Purpose: To analyze retrospectively the results of external beam radiotherapy for clinically localized hormone-refractory prostate cancer and investigate the clinical significance of nadir prostate-specific antigen (PSA) value within 12 months (nPSA12) as an early estimate of clinical outcomes after radiotherapy. Methods and Materials: Eighty-four patients with localized hormone-refractory prostate cancer treated with external beam radiotherapy were retrospectively reviewed. The total radiation doses ranged from 30 to 76 Gy (median, 66 Gy), and the median follow-up period for all 84 patients was 26.9 months (range, 2.7-77.3 months). Results: The 3-year actuarial overall survival, progression-free survival (PFS), and local control rates in all 84 patients after radiotherapy were 67%, 61%, and 93%, respectively. Although distant metastases and/or regional lymph node metastases developed in 34 patients (40%) after radiotherapy, local progression was observed in only 5 patients (6%). Of all 84 patients, the median nPSA12 in patients with clinical failure and in patients without clinical failure was 3.1 ng/mL and 0.5 ng/mL, respectively. When dividing patients according to low (<0.5 ng/mL) and high ({>=}0.5 ng/mL) nPSA12 levels, the 3-year PFS rate in patients with low nPSA12 and in those with high nPSA12 was 96% and 44%, respectively (p < 0.0001). In univariate analysis, nPSA12 and pretreatment PSA value had a significant impact on PFS, and in multivariate analysis nPSA12 alone was an independent prognostic factor for PFS after radiotherapy. Conclusions: External beam radiotherapy had an excellent local control rate for clinically localized hormone-refractory prostate cancer, and nPSA12 was predictive of clinical outcomes after radiotherapy.

  6. Quality control of radiation therapy in multi-institutional randomized clinical trial for localized prostate cancer

    SciTech Connect

    Hafermann, M.D.; Gibbons, R.P.; Murphy, G.P.

    1988-02-01

    The National Prostatic Cancer Project (NPCP) from 1978 through 1985 compared definitive radiation therapy for Stages B2, C, D1 lesions in those who received only radiation treatment to those who received two years of additional cyclophosphamide (Cytoxan) or estramustine phosphate (Emcyt) chemotherapy. Two hundred fifty-four patients were entered and 229 evaluated for compliance of the spatial localization of the prostate through review of the simulation and port films. In 78 per cent this was satisfactory, whereas in 12 per cent it was unsatisfactory, and another 10 per cent were not evaluable. The principle cause of an unsatisfactory rating was failure to adequately cover the prostatic target volume, especially the apex which was found to be variable in location. Routine use of retrograde urethrocystography is urged as part of the localization method in patients to receive definitive external beam radiation therapy for prostate cancer. The role and impact of quality assurance programs for radiotherapy in cooperative clinical study groups is reviewed and discussed.

  7. Significance of Image Guidance to Clinical Outcomes for Localized Prostate Cancer

    PubMed Central

    Zhong, Qiuzi; Gao, Hong; Li, Gaofeng; Xiu, Xia; Wu, Qinhong; Li, Ming; Xu, Yonggang

    2014-01-01

    Purpose. To compare toxicity profiles and biochemical tumor control outcomes between patients treated with image-guided intensity-modulated radiotherapy (IG-IMRT) and non-IGRT intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. Materials and Methods. Between 2009 and 2012, 65 patients with localized prostate cancer were treated with IG-IMRT. This group of patients was retrospectively compared with a similar cohort of 62 patients who were treated between 2004 and 2009 with IMRT to the same dose without image guidance. Results. The median follow-up time was 4.8 years. The rectal volume receiving ≥40 and ≥70 Gy was significantly lower in the IG-IMRT group. Grade 2 and higher acute and late GI and GU toxicity rates were lower in IG-IMRT group, but there was no statistical difference. No significant improvement in biochemical control at 5 years was observed in two groups. In a Cox regression analysis identifying predictors for PSA relapse-free survival, only preradiotherapy PSA was significantly associated with biochemical control; IG-IMRT was not a statistically significant indicator. Conclusions. The use of image guidance in the radiation of prostate cancer at our institute did not show significant reduction in the rates of GI and GU toxicity and did not improve the biochemical control compared with IMRT. PMID:25110701

  8. Interobserver consistency of digital rectal examination in clinical staging of localized prostatic carcinoma.

    PubMed

    Angulo, J C; Montie, J E; Bukowsky, T; Chakrabarty, A; Grignon, D J; Sakr, W; Shamsa, F H; Edson Pontes, J

    1995-01-01

    A prospective study was undertaken to determine the reproducibility of clinical staging based on digital rectal examination (DRE) in prostate carcinoma. We evaluated 48 consecutive patients diagnosed with localized prostatic cancer. Four urologists performed DRE and sorted the patients according to the 1992 American Joint Committee on Cancer Classification for prostate cancer. Both the percentage observed total agreement among each couple of two different observers and the interobserver variability (Kappa index) were analyzed. The percentage observed total agreement among observers in distinguishing five clinical subcategories (T1c, T2a, T2b, T2c, and T3a) ranged between 38-60% (mean 49%) and the Kappa index showed interobserver agreement was poor (overall Kappa = 0.3 1). All four examiners agreed in assigning the same subcategory in only 21 % of cases, and 90% of them were T I. If only categories are distinguished (T I, T2, or T3), the percentage observed total agreement rises to 60-71% (mean 66%) and the interexaminer agreement improves to good (overall Kappa = 0.4 1). Accurate pathologic staging was obtained in every patient and the percentage observed agreement between every examiner and the pathologist was calculated, excluding cases interpreted as T I c. Regarding subcategories, clinicopathologic agreement ranges between 17-46%. If only categories T2 and9T3 are distinguished, agreement rises to 57-69%. In summary, the ability to reproduce clinical staging based on DRE among multiple examiners is disappointingly low and understandably correlates poorly with pathologic stage.

  9. Short-, Intermediate-, and Long-term Quality of Life Outcomes Following Radical Prostatectomy for Clinically Localized Prostate Cancer

    PubMed Central

    Prabhu, Vinay; Lee, Ted; McClintock, Tyler R; Lepor, Herbert

    2013-01-01

    Many clinically localized prostate cancers that are diagnosed today are low risk, and prevention of disease-specific mortality may only be realized decades after treatment. Radical prostatectomy (RP) may adversely impact health-related quality of life (HRQOL) by causing both transient or permanent urinary incontinence and erectile dysfunction. In contrast, RP may also improve HRQOL via relief of lower urinary tract symptoms in men suffering from these symptoms prior to surgery. Because the average man treated for prostate cancer has a life expectancy of approximately 14 years, it is imperative to consider the long-term impact of RP on both survival and HRQOL in treatment decision making. This comprehensive literature review examines short-, intermediate-, and long-term HRQOL following RP. In addition, the long-term results of RP are compared with other treatment modalities for treating clinically localized prostate cancer. PMID:24659913

  10. Incorporation of tissue-based genomic biomarkers into localized prostate cancer clinics.

    PubMed

    Moschini, Marco; Spahn, Martin; Mattei, Agostino; Cheville, John; Karnes, R Jeffrey

    2016-01-01

    Localized prostate cancer (PCa) is a clinically heterogeneous disease, which presents with variability in patient outcomes within the same risk stratification (low, intermediate or high) and even within the same Gleason scores. Genomic tools have been developed with the purpose of stratifying patients affected by this disease to help physicians personalize therapies and follow-up schemes. This review focuses on these tissue-based tools. At present, four genomic tools are commercially available: Decipher™, Oncotype DX®, Prolaris® and ProMark®. Decipher™ is a tool based on 22 genes and evaluates the risk of adverse outcomes (metastasis) after radical prostatectomy (RP). Oncotype DX® is based on 17 genes and focuses on the ability to predict outcomes (adverse pathology) in very low-low and low-intermediate PCa patients, while Prolaris® is built on a panel of 46 genes and is validated to evaluate outcomes for patients at low risk as well as patients who are affected by high risk PCa and post-RP. Finally, ProMark® is based on a multiplexed proteomics assay and predicts PCa aggressiveness in patients found with similar features to Oncotype DX®. These biomarkers can be helpful for post-biopsy decision-making in low risk patients and post-radical prostatectomy in selected risk groups. Further studies are needed to investigate the clinical benefit of these new technologies, the financial ramifications and how they should be utilized in clinics. PMID:27044421

  11. Prostatitis--clinical and bacterial studies.

    PubMed

    Chandiok, S; Fisk, P G; Riley, V C

    1992-01-01

    Forty men with clinical prostatitis were studied to determine the value of symptomatology and categorization and 30 (75%) were classified as having prostatitis on the basis of prostatic localization studies. Of these 3 (10%) had chronic bacterial prostatitis, 18 (60%) had chronic abacterial prostatitis, and 9 (30%) had prostatodynia. No patient had acute bacterial prostatitis. Although Enterobacteriaciae were isolated from the 3 men with chronic bacterial prostatitis, these bacteria along with Staphlococcus aureus, Streptococcus faecalis, and Chlamydia trachomatis were isolated from a further 6 patients. The mean pH of the expressed prostatic secretion was measured for each group and was found to be 7.6 for those with chronic bacterial prostatitis, 7.1 for chronic abacterial prostatitis, 6.5 for prostatodynia, and 6.9 for those with urethritis suggesting that this test may be of value in the diagnosis of chronic bacterial prostatitis.

  12. The Matrix Metalloproteinase-7 Polymorphism Rs10895304 Is Associated With Increased Recurrence Risk in Patients With Clinically Localized Prostate Cancer

    SciTech Connect

    Jaboin, Jerry J.; Hwang, Misun; Lopater, Zachary; Chen Heidi; Ray, Geoffrey L.; Perez, Carmen; Cai Qiuyin; Wills, Marcia L.; Lu Bo

    2011-04-01

    Purpose: To evaluate whether selected high-risk matrix metalloproteinase-7 single nucleotide polymorphisms influence clinicopathologic outcomes in patients with early-stage prostate cancer. Methods and Materials: Two hundred twelve prostate cancer patients treated with radical prostatectomy were evaluated with a median follow-up of 9.8 years. Genotyping was performed using hybridization with custom-designed allele-specific probes. Three single nucleotide polymorphisms within the matrix metalloproteinase-7 gene were assessed with respect to age at diagnosis, margin status, extracapsular extension, lymph node involvement, recurrence-free survival, and overall survival in paraffin-embedded prostate tissue specimens from patients with early-stage prostate cancer who underwent radical prostatectomy. Results: Rs10895304 was the sole significant polymorphism. The A/G genotype of rs10895304 had a statistically significant association with recurrence-free survival in postprostatectomy patients (p = 0.0061, log-rank test). The frequency of the risk-reducing genotype (A/A) was 74%, whereas that of the risk-enhancing genotypes (A/G and G/G) were 20% and 6%, respectively. Multivariable Cox regression analyses detected a significant association between rs10895304 and recurrences after adjustment for known prognostic factors. The G allele of this polymorphism was associated with increased risk of prostate cancer recurrence (adjusted hazards ratio, 3.375; 95% confidence interval 1.567-7.269; p < 0.001). The other assayed polymorphisms were not significant, and no correlations were made to other clinical variables. Conclusions: The A/G genotype of rs10895304 is predictive of decreased recurrence-free survival in patients with clinically localized prostate cancer. Our data suggest that for this subset of patients, prostatectomy alone may not be adequate for local control. This is a novel and relevant marker that should be evaluated for improved risk stratification of patients who

  13. Effect of Family History on Outcomes in Patients Treated With Definitive Brachytherapy for Clinically Localized Prostate Cancer

    SciTech Connect

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

    2009-01-01

    Purpose: To determine the impact familial prostate cancer has on prognosis in men treated with brachytherapy for clinically localized prostate cancer. Methods and Materials: 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). Results: 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. Conclusions: 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.

  14. Health-Related Quality of Life 2 Years After Treatment With Radical Prostatectomy, Prostate Brachytherapy, or External Beam Radiotherapy in Patients With Clinically Localized Prostate Cancer

    SciTech Connect

    Ferrer, Montserrat Suarez, Jose Francisco; Guedea, Ferran; Fernandez, Pablo; Macias, Victor; Marino, Alfonso; Hervas, Asuncion; Herruzo, Ismael; Ortiz, Maria Jose; Villavicencio, Humberto; Craven-Bratle, Jordi; Garin, Olatz; Aguilo, Ferran

    2008-10-01

    Purpose: To compare treatment impact on health-related quality of life (HRQL) in patients with localized prostate cancer, from before treatment to 2 years after the intervention. Methods and Materials: This was a longitudinal, prospective study of 614 patients with localized prostate cancer treated with radical prostatectomy (134), three-dimensional external conformal radiotherapy (205), and brachytherapy (275). The HRQL questionnaires administered before and after treatment (months 1, 3, 6, 12, and 24) were the Medical Outcomes Study 36-Item Short Form, the Functional Assessment of Cancer Therapy (General and Prostate Specific), the Expanded Prostate Cancer Index Composite (EPIC), and the American Urological Association Symptom Index. Differences between groups were tested by analysis of variance and within-group changes by univariate repeated-measures analysis of variance. Generalized estimating equations (GEE) models were constructed to assess between-group differences in HRQL at 2 years of follow-up after adjusting for clinical variables. Results: In each treatment group, HRQL initially deteriorated after treatment with subsequent partial recovery. However, some dimension scores were still significantly lower after 2 years of treatment. The GEE models showed that, compared with the brachytherapy group, radical prostatectomy patients had worse EPIC sexual summary and urinary incontinence scores (-20.4 and -14.1; p < 0.001), and external radiotherapy patients had worse EPIC bowel, sexual, and hormonal summary scores (-3.55, -5.24, and -1.94; p < 0.05). Prostatectomy patients had significantly better EPIC urinary irritation scores than brachytherapy patients (+4.16; p < 0.001). Conclusions: Relevant differences between treatment groups persisted after 2 years of follow-up. Radical prostatectomy had a considerable negative effect on sexual functioning and urinary continence. Three-dimensional conformal radiotherapy had a moderate negative impact on bowel

  15. Neoadjuvant Treatment of High-Risk, Clinically Localized Prostate Cancer Prior to Radical Prostatectomy.

    PubMed

    Pietzak, Eugene J; Eastham, James A

    2016-05-01

    Multimodal strategies combining local and systemic therapy offer the greatest chance of cure for many with men with high-risk prostate cancer who may harbor occult metastatic disease. However, no systemic therapy combined with radical prostatectomy has proven beneficial. This was in part due to a lack of effective systemic agents; however, there have been several advancements in the metastatic and castrate-resistant prostate cancer that might prove beneficial if given earlier in the natural history of the disease. For example, novel hormonal agents have recently been approved for castration-resistant prostate cancer with some early phase II neoadjuvant showing promise. Additionally, combination therapy with docetaxel-based chemohormonal has demonstrated a profound survival benefit in metastatic hormone-naïve patients and might have a role in eliminating pre-existing ADT-resistant tumor cells in the neoadjuvant setting. The Cancer and Leukemia Group B (CALGB)/Alliance 90203 trial has finished accrual and should answer the question as to whether neoadjuvant docetaxel-based chemohormonal therapy provides an advantage over prostatectomy alone. There are also several promising targeted agents and immunotherapies under investigation in phase I/II trials with the potential to provide benefit in the neoadjuvant setting. PMID:26968417

  16. Distant Metastases Following Permanent Interstitial Brachytherapy for Patients With Clinically Localized Prostate Cancer

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Lief, Jonathan; Adamovich, Edward; Wallner, Kent E.

    2012-02-01

    Purpose: Recent publications have suggested high-risk patients undergoing radical prostatectomy have a lower risk of distant metastases and improved cause-specific survival (CSS) than patients receiving definitive external beam radiation therapy (XRT). To date, none of these studies has compared distant metastases and CSS in brachytherapy patients. In this study, we evaluate such parameters in a consecutive cohort of brachytherapy patients. Methods and Materials: From April 1995 to June 2007, 1,840 consecutive patients with clinically localized prostate cancer were treated with brachytherapy. Risk groups were stratified according to National Comprehensive Cancer Network ( (www.nccn.org)) guidelines. Subgroups of 658, 893, and 289 patients were assigned to low, intermediate, and high-risk categories. Median follow-up was 7.2 years. Along with brachytherapy implantation, 901 (49.0%) patients received supplemental XRT, and 670 (36.4%) patients received androgen deprivation therapy (median duration, 4 months). The mode of failure (biochemical, local, or distant) was determined for each patient for whom therapy failed. Cause of death was determined for each deceased patient. Multiple parameters were evaluated for impact on outcome. Results: For the entire cohort, metastases-free survival (MFS) and CSS at 12 years were 98.1% and 98.2%, respectively. When rates were stratified by low, intermediate, and high-risk groups, the 12-year MFS was 99.8%, 98.1%, and 93.8% (p < 0.001), respectively. CSS rates were 99.8%, 98.0%, and 95.3% (p < 0.001) for low, intermediate, and high-risk groups, respectively. Biochemical progression-free survival was 98.7%, 95.9% and 90.4% for low, intermediate, and high-risk patients, respectively (p < 0.001). In multivariate Cox-regression analysis, MFS was mostly closely related to Gleason score and year of treatment, whereas CSS was most closely associated with Gleason score. Conclusions: Excellent CSS and MFS rates are achievable with high

  17. High-Dose-Rate Interstitial Brachytherapy as Monotherapy for Clinically Localized Prostate Cancer: Treatment Evolution and Mature Results

    SciTech Connect

    Zamboglou, Nikolaos; Tselis, Nikolaos; Baltas, Dimos; Buhleier, Thomas; Martin, Thomas; Milickovic, Natasa; Papaioannou, Sokratis; Ackermann, Hanns; Tunn, Ulf W.

    2013-03-01

    Purpose: To report the clinical outcome of high-dose-rate (HDR) interstitial (IRT) brachytherapy (BRT) as sole treatment (monotherapy) for clinically localized prostate cancer. Methods and Materials: Between January 2002 and December 2009, 718 consecutive patients with clinically localized prostate cancer were treated with transrectal ultrasound (TRUS)-guided HDR monotherapy. Three treatment protocols were applied; 141 patients received 38.0 Gy using one implant in 4 fractions of 9.5 Gy with computed tomography-based treatment planning; 351 patients received 38.0 Gy in 4 fractions of 9.5 Gy, using 2 implants (2 weeks apart) and intraoperative TRUS real-time treatment planning; and 226 patients received 34.5 Gy, using 3 single-fraction implants of 11.5 Gy (3 weeks apart) and intraoperative TRUS real-time treatment planning. Biochemical failure was defined according to the Phoenix consensus, and toxicity was evaluated using Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 52.8 months. The 36-, 60-, and 96-month biochemical control and metastasis-free survival rates for the entire cohort were 97%, 94%, and 90% and 99%, 98%, and 97%, respectively. Toxicity was scored per event, with 5.4% acute grade 3 genitourinary and 0.2% acute grade 3 gastrointestinal toxicity. Late grade 3 genitourinary and gastrointestinal toxicities were 3.5% and 1.6%, respectively. Two patients developed grade 4 incontinence. No other instance of grade 4 or greater acute or late toxicity was reported. Conclusion: Our results confirm IRT-HDR-BRT is safe and effective as monotherapy for clinically localized prostate cancer.

  18. Radical External Beam Radiotherapy for Clinically Localized Prostate Cancer in Japan: Changing Trends in the Patterns of Care Process Survey

    SciTech Connect

    Ogawa, Kazuhiko; Nakamura, Katsumasa; Sasaki, Tomonari; Onishi, Hiroshi; Koizumi, Masahiko; Araya, Masayuki; Mukumoto, Nobutaka; Teshima, Teruki; Mitsumori, Michihide

    2011-12-01

    Purpose: To delineate changing trends in radical external beam radiotherapy (EBRT) for prostate cancer in Japan. Methods and Materials: Data from 841 patients with clinically localized prostate cancer treated with EBRT in the Japanese Patterns of Care Study (PCS) from 1996 to 2005 were analyzed. Results: Significant increases in the proportions of patients with stage T1 to T2 disease and decrease in prostate-specific antigen values were observed. Also, there were significant increases in the percentages of patients treated with radiotherapy by their own choice. Median radiation doses were 65.0 Gy and 68.4 Gy from 1996 to 1998 and from 1999 to 2001, respectively, increasing to 70 Gy from 2003 to 2005. Moreover, conformal therapy was more frequently used from 2003 to 2005 (84.9%) than from 1996 to 1998 (49.1%) and from 1999 to 2001 (50.2%). On the other hand, the percentage of patients receiving hormone therapy from 2003 to 2005 (81.1%) was almost the same as that from 1996 to 1998 (86.3%) and from 1999 to 2001 (89.7%). Compared with the PCS in the United States, patient characteristics and patterns of treatments from 2003 to 2005 have become more similar to those in the United States than those from 1996 to 1998 and those from 1999 to 2001. Conclusions: This study indicates a trend toward increasing numbers of patients with early-stage disease and increasing proportions of patients treated with higher radiation doses with advanced equipment among Japanese prostate cancer patients treated with EBRT during 1996 to 2005 survey periods. Patterns of care for prostate cancer in Japan are becoming more similar to those in the United States.

  19. Multiparametric magnetic resonance imaging for pre-treatment local staging of prostate cancer: A Cancer Care Ontario clinical practice guideline

    PubMed Central

    Salerno, Jennifer; Finelli, Antonio; Morash, Chris; Morgan, Scott C.; Power, Nicholas; Schieda, Nichola; Haider, Masoom A.

    2016-01-01

    Introduction: The utility of T2-weighted magnetic resonance imaging (MRI) in the local staging of prostate cancer is controversial. Due to the success of multiparametric MRI in cancer localization, there is renewed interested in MRI (± functional sequences) for local staging. Guidance on pre-treatment local staging of prostate cancer by MRI was developed using systematic review methodology and expert consultation. Methods: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and other databases were searched to identify studies comparing: (1) MRI staging vs. radical prostatectomy staging on diagnostic accuracy outcomes; and (2) MRI staging vs. routine clinical staging on clinical and patient outcomes. Studies meeting inclusion criteria were synthesized by outcome and sensitivity/specificity analysis by tumour location was performed. Evidence quality of included studies was assessed and considered in recommendation formulation. Results: The literature search identified 2510 citations; 62 studies were included. Analysis of MRI ≥1.5 T plus endorectal coil (ER) (± functional sequences) in the detection of extraprostatic extension or seminal vesicle invasion showed modest sensitivities (≥50%) and excellent specificities (>85%) among patients scheduled for radical prostatectomy. MRI upstaging was shown in 20/21 studies, with large variation in correctness (11–85%). Scarcity of clinical and patient outcomes among studies limited synthesis and evaluation. Quality assessment found non-trivial biases. Conclusions: Modest imaging performance was shown for MRI (1.5 T + ER and 3 T ± ER) ± functional sequences in regards to sensitivity. Limitations in study design, reporting of clinical and patient outcomes, and the heterogeneous use of MRI tempered the strength of the recommendations. PMID:27800062

  20. The Prostate Cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy with watchful waiting for men with clinically localized prostate cancer.

    PubMed

    Wilt, Timothy J

    2012-12-01

    Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. In the United States, 90% of men with prostate cancer are more than age 60 years, diagnosed by early detection with the prostate-specific antigen (PSA) blood test, and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting (WW), surgery to remove the prostate gland (radical prostatectomy), external-beam radiation therapy and interstitial radiation therapy (brachytherapy), and androgen deprivation. Little is known about the relative effectiveness and harms of treatments because of the paucity of randomized controlled trials. The Department of Veterans Affairs/National Cancer Institute/Agency for Healthcare Research and Quality Cooperative Studies Program Study #407:Prostate Cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy with WW in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods, and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy vs WW conducted in Scandinavia. We screened 13 022 men with prostate cancer at 52 US medical centers for potential enrollment. From these, 5023 met initial age, comorbidity, and disease eligibility criteria, and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African American. Approximately 85% reported that they were fully active. The median PSA was 7.8ng/mL (mean 10.2ng/mL). In three-fourths of men, the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk

  1. The Prostate Cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy with watchful waiting for men with clinically localized prostate cancer.

    PubMed

    Wilt, Timothy J

    2012-12-01

    Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. In the United States, 90% of men with prostate cancer are more than age 60 years, diagnosed by early detection with the prostate-specific antigen (PSA) blood test, and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting (WW), surgery to remove the prostate gland (radical prostatectomy), external-beam radiation therapy and interstitial radiation therapy (brachytherapy), and androgen deprivation. Little is known about the relative effectiveness and harms of treatments because of the paucity of randomized controlled trials. The Department of Veterans Affairs/National Cancer Institute/Agency for Healthcare Research and Quality Cooperative Studies Program Study #407:Prostate Cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy with WW in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods, and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy vs WW conducted in Scandinavia. We screened 13 022 men with prostate cancer at 52 US medical centers for potential enrollment. From these, 5023 met initial age, comorbidity, and disease eligibility criteria, and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African American. Approximately 85% reported that they were fully active. The median PSA was 7.8ng/mL (mean 10.2ng/mL). In three-fourths of men, the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk

  2. Long-Term Outcome for Clinically Localized Prostate Cancer Treated With Permanent Interstitial Brachytherapy

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S.; Butler, Wayne M.; Galbreath, Robert W.; Lief, Jonathan; Adamovich, Edward; Wallner, Kent E.

    2011-04-01

    Purpose: To present the largest series of prostate cancer brachytherapy patients treated with modern brachytherapy techniques and postimplant day 0 dosimetric evaluation. Methods and Materials: Between April 1995 and July 2006, 1,656 consecutive patients were treated with permanent interstitial brachytherapy. Risk group stratification was carried out according to the Mt. Sinai guidelines. Median follow-up was 7.0 years. The median day 0 minimum dose covering at least 90% of the target volume was 118.8% of the prescription dose. Cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters. Results: At 12 years, biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) for the entire cohort was 95.6%, 98.2%, and 72.6%, respectively. For low-, intermediate-, and high-risk patients, bPFS was 98.6%, 96.5%, and 90.5%; CSS was 99.8%, 99.3%, and 95.2%; and OS was 77.5%, 71.1%, and 69.2%, respectively. For biochemically controlled patients, the median posttreatment prostate-specific antigen (PSA) concentration was 0.02 ng/ml. bPFS was most closely related to percent positive biopsy specimens and risk group, while Gleason score was the strongest predictor of CSS. OS was best predicted by patient age, hypertension, diabetes, and tobacco use. At 12 years, biochemical failure and cause-specific mortality were 1.8% and 0.2%, 5.1% and 2.1%, and 10.4% and 7.1% for Gleason scores 5 to 6 and 7 and {>=}8, respectively. Conclusions: Excellent long-term outcomes are achievable with high-quality brachytherapy for low-, intermediate-, and high-risk patients. These results compare favorably to alternative treatment modalities including radical prostatectomy.

  3. Tissue ablation technologies for localized prostate cancer.

    PubMed

    Gillett, Michael D; Gettman, Matthew T; Zincke, Horst; Blute, Michael L

    2004-12-01

    Traditional treatments for men with localized prostate cancer have included both surgical removal and radiation therapy, with their potential adverse effects on patient quality of life. Thus, there has been increasing interest in the development of minimally invasive procedures that use various technologies to deliver lethal doses of heat or cold to the prostate in an attempt to kill cancer cells. At the same time, it is vital that these newer techniques ablate prostate tissue and spare vital periprostatic organs essential for maintaining function and quality of life. In this article, we evaluate the current status of tissue ablation modalities in the treatment of clinically localized prostate cancer, focusing on the different methods, early results, and possible future directions. Although still in the beginning stages, these newer forms of treatment offer exciting potential for first-line and second-line treatment of this common urologic malignancy.

  4. Biomarkers in localized prostate cancer.

    PubMed

    Ferro, Matteo; Buonerba, Carlo; Terracciano, Daniela; Lucarelli, Giuseppe; Cosimato, Vincenzo; Bottero, Danilo; Deliu, Victor M; Ditonno, Pasquale; Perdonà, Sisto; Autorino, Riccardo; Coman, Ioman; De Placido, Sabino; Di Lorenzo, Giuseppe; De Cobelli, Ottavio

    2016-02-01

    Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer.

  5. Cryosurgery would be An Effective Option for Clinically Localized Prostate Cancer: A Meta-analysis and Systematic Review

    PubMed Central

    Gao, Liang; Yang, Lu; Qian, Shengqiang; Tang, Zhuang; Qin, Feng; Wei, Qiang; Han, Ping; Yuan, Jiuhong

    2016-01-01

    Cryosurgery (CS) has been used on patients with clinically localized PCa for more than 10 years. However, clinical studies evaluating its effectiveness and safety have reported conflicting results. This systematic assessment was performed to obtain comprehensive evidence regarding the potential benefits and safety of CS compared with those of radiotherapy (RT) and radical prostatectomy (RP), respectively. All controlled trials comparing CS with RT or RP and single-arm studies reporting results of CS therapy were identified through comprehensive searches of PubMed, the Cochrane Library and Embase. Ten publications from seven trials, with totally 1252 patients, were included in the meta-analysis, which revealed no significant differences in comparisons of CS vs RT and CS vs RP for overall survival and disease specific survival. However, a significantly lower disease-free survival could be observed for CS than RP. Moreover, a systematic review of literature focusing on comparative data of databases and materials of single-arm trials revealed satisfactory survival results in both primary and salvage CS. Our results showed that cryosurgery would be a relatively effective method for clinically localized prostate cancer with survival results comparable to radiotherapy and radical prostatectomy. However, the large percentage of complications caused by cryosurgery should be carefully monitored. PMID:27271239

  6. Intermittent androgen deprivation (IAD) in patients with biochemical failure after radical retropubic prostatectomy (RRP) for clinically localized prostate cancer.

    PubMed

    Sciarra, A; Di Chiro, C; Di Silverio, F

    2000-12-01

    We report a study in which our objective was to analyze the clinical response during IAD in patients with biochemical failure after RRP for clinically localized prostate cancer. Between February 1994 and May 1996, 34 patients who exhibited a primary postoperative decrease in PSA to below the detection limit after RRP and then showed PSA progression during follow-up were included as group 1 and 17 patients in whom PSA did not decrease after RRP were included as group 2. Patients were offered IAD when PSA progressed over 0.4 ng/ml in group 1 and over 4.0 ng/ml in group 2. Median follow-up is 184 weeks in group 1 and 206 weeks in group 2. The median time "off" therapy increased from 25% (1st cycle) to 68.7% (5th cycle) of the entire cycle in group 1 and from 33.3% to 58.3% in group 2. Nine out of 12 cases with Gleason score > or =8 failed to respond to IAD and all developed metastatic and/or local failure. No case with Gleason score <7 failed to respond to IAD. Our conclusions suggest that IAD may be effective in patients with biochemical progression after RRP. In our experience, Gleason score seems to be an important variable.

  7. Retrospective Comparison of External Beam Radiotherapy and Radical Prostatectomy in High-Risk, Clinically Localized Prostate Cancer

    SciTech Connect

    Arcangeli, Giorgio; Strigari, Lidia; Arcangeli, Stefano; Petrongari, Maria Grazia; Saracino, Biancamaria; Gomellini, Sara; Papalia, Rocco; Simone, Giuseppe; De Carli, Piero; Gallucci, Michele

    2009-11-15

    Purpose: Because of the lack of conclusive and well-conducted randomized studies, the optimal therapy for prostate tumors remains controversial. The aim of this study was to retrospectively compare the results of radical surgery vs. a conservative approach such as external beam radiotherapy (EBRT) plus androgen deprivation therapy using an intent-to-treat analysis on two pretreatment defined, concurrently treated, high-risk patient populations. Methods and Materials: Between January 2003 and December 2007, 162 patients with high-risk prostate cancer underwent an EBRT plus androgen deprivation therapy program at the RT department of our institute. In the same period, 122 patients with the same high-risk disease underwent radical prostatectomy (RP) at the urologic department of our institute. Patients with adverse pathologic factors also underwent adjuvant EBRT with or without androgen deprivation therapy. The primary endpoint was freedom from biochemical failure. Results: The two groups of high-risk patients were homogeneous in terms of freedom from biochemical failure on the basis of the clinical T stage, biopsy Gleason score, and initial prostate-specific antigen level. The median follow-up was 38.6 and 33.8 months in the EBRT and RP groups, respectively. The actuarial analysis of the freedom from biochemical failure showed a 3-year rate of 86.8% and 69.8% in the EBRT and RP group, respectively (p = .001). Multivariate analysis of the whole group revealed the initial prostate-specific antigen level and treatment type (EBRT vs. RP) as significant covariates. Conclusion: This retrospective intention-to-treat analysis showed a significantly better outcome after EBRT than after RP in patients with high-risk prostate cancer, although a well-conducted randomized comparison would be the best procedure to confirm these results.

  8. Prostate cancer: multiparametric MR imaging for detection, localization, and staging.

    PubMed

    Hoeks, Caroline M A; Barentsz, Jelle O; Hambrock, Thomas; Yakar, Derya; Somford, Diederik M; Heijmink, Stijn W T P J; Scheenen, Tom W J; Vos, Pieter C; Huisman, Henkjan; van Oort, Inge M; Witjes, J Alfred; Heerschap, Arend; Fütterer, Jurgen J

    2011-10-01

    This review presents the current state of the art regarding multiparametric magnetic resonance (MR) imaging of prostate cancer. Technical requirements and clinical indications for the use of multiparametric MR imaging in detection, localization, characterization, staging, biopsy guidance, and active surveillance of prostate cancer are discussed. Although reported accuracies of the separate and combined multiparametric MR imaging techniques vary for diverse clinical prostate cancer indications, multiparametric MR imaging of the prostate has shown promising results and may be of additional value in prostate cancer localization and local staging. Consensus on which technical approaches (field strengths, sequences, use of an endorectal coil) and combination of multiparametric MR imaging techniques should be used for specific clinical indications remains a challenge. Because guidelines are currently lacking, suggestions for a general minimal protocol for multiparametric MR imaging of the prostate based on the literature and the authors' experience are presented. Computer programs that allow evaluation of the various components of a multiparametric MR imaging examination in one view should be developed. In this way, an integrated interpretation of anatomic and functional MR imaging techniques in a multiparametric MR imaging examination is possible. Education and experience of specialist radiologists are essential for correct interpretation of multiparametric prostate MR imaging findings. Supportive techniques, such as computer-aided diagnosis are needed to obtain a fast, cost-effective, easy, and more reproducible prostate cancer diagnosis out of more and more complex multiparametric MR imaging data. PMID:21931141

  9. Overview of Randomized Controlled Treatment Trials for Clinically Localized Prostate Cancer: Implications for Active Surveillance and the United States Preventative Task Force Report on Screening?

    PubMed Central

    2012-01-01

    Prostate cancer and its management have been intensely debated for years. Recommendations range from ardent support for active screening and immediate treatment to resolute avoidance of screening and active surveillance. There is a growing body of level I evidence establishing a clear survival advantage for treatment of subsets of patients with clinically localized prostate cancer. This chapter presents a review of these randomized controlled trials. We argue that an understanding of this literature is relevant not only to those considering active surveillance but also to those evaluating the merits of screening. In addition, a number of important evidence-based conclusions concerning what should and should not be done can be gleaned from these trials. PMID:23271777

  10. Five-year outcome of intraoperative conformal permanent I-125 interstitial implantation for patients with clinically localized prostate cancer

    SciTech Connect

    Zelefsky, Michael J. . E-mail: zelefskm@mskcc.org; Yamada, Yoshiya; Cohen, Gil'ad N.; Shippy, Alison; Chan, Heather; Fridman, David; Zaider, Marco

    2007-01-01

    Purpose: To report the 5-year tumor control and toxicity outcomes for patients with localized prostate treated with I-125 permanent implantation using an intraoperative real-time conformal planning technique. Methods and Materials: Between January 1998 and June 2002, 367 patients with prostate cancer were treated with I-125 permanent interstitial implantation using a transrectal ultrasound-guided approach. Real-time intraoperative treatment planning which incorporated inverse planning optimization was used. The median follow-up time was 63 months. Results: The median V100 and D90 were 96% and 173 Gy, respectively. In 96% of cases a D90 of >140 Gy was achieved. The median urethral and rectal doses were 100% and 33% of the prescription doses, respectively. The 5-year PSA relapse-free survival outcomes for favorable and intermediate risk patients according to the ASTRO definition were 96% and 89%, respectively. In these patients no dosimetric parameter was identified which influenced the biochemical outcome. Of 38% who developed acute Grade 2 urinary symptoms, 63% had resolution of their symptoms within a median time of 6 months. The incidence of late rectal and urinary Grade 3 or higher toxicities were 1% and 4%, respectively. Seven percent (n = 27) developed late rectal bleeding (Grade 2) and 19% experienced late Grade 2 urinary symptoms. Conclusion: Real-time intraoperative planning consistently achieved optimal coverage of the prostate with the prescription dose with concomitant low doses delivered to the urethra and rectum. Biochemical control outcomes were excellent at 5 years and late toxicity was unusual. These data demonstrate that real-time planning methods can consistently and reliably deliver the intended dose distribution to achieve an optimal therapeutic ratio between the target and normal tissue structures.

  11. Mapping of nodal disease in locally advanced prostate cancer: Rethinking the clinical target volume for pelvic nodal irradiation based on vascular rather than bony anatomy

    SciTech Connect

    Shih, Helen A. . E-mail: hshih@partners.org; Harisinghani, Mukesh; Zietman, Anthony L.; Wolfgang, John A.; Saksena, Mansi; Weissleder, Ralph

    2005-11-15

    Purpose: Toxicity from pelvic irradiation could be reduced if fields were limited to likely areas of nodal involvement rather than using the standard 'four-field box.' We employed a novel magnetic resonance lymphangiographic technique to highlight the likely sites of occult nodal metastasis from prostate cancer. Methods and Materials: Eighteen prostate cancer patients with pathologically confirmed node-positive disease had a total of 69 pathologic nodes identifiable by lymphotropic nanoparticle-enhanced MRI and semiquantitative nodal analysis. Fourteen of these nodes were in the para-aortic region, and 55 were in the pelvis. The position of each of these malignant nodes was mapped to a common template based on its relation to skeletal or vascular anatomy. Results: Relative to skeletal anatomy, nodes covered a diffuse volume from the mid lumbar spine to the superior pubic ramus and along the sacrum and pelvic side walls. In contrast, the nodal metastases mapped much more tightly relative to the large pelvic vessels. A proposed pelvic clinical target volume to encompass the region at greatest risk of containing occult nodal metastases would include a 2.0-cm radial expansion volume around the distal common iliac and proximal external and internal iliac vessels that would encompass 94.5% of the pelvic nodes at risk as defined by our node-positive prostate cancer patient cohort. Conclusions: Nodal metastases from prostate cancer are largely localized along the major pelvic vasculature. Defining nodal radiation treatment portals based on vascular rather than bony anatomy may allow for a significant decrease in normal pelvic tissue irradiation and its associated toxicities.

  12. Preoperative 3-Tesla Multiparametric Endorectal Magnetic Resonance Imaging Findings and the Odds of Upgrading and Upstaging at Radical Prostatectomy in Men With Clinically Localized Prostate Cancer

    SciTech Connect

    Hegde, John V.; Chen, Ming-Hui; Mulkern, Robert V.; Fennessy, Fiona M.; D'Amico, Anthony V.; Tempany, Clare M.C.

    2013-02-01

    Purpose: To investigate whether 3-T esla (3T) multiparametric endorectal MRI (erMRI) can add information to established predictors regarding occult extraprostatic or high-grade prostate cancer (PC) in men with clinically localized PC. Methods and Materials: At a single academic medical center, this retrospective study's cohort included 118 men with clinically localized PC who underwent 3T multiparametric erMRI followed by radical prostatectomy, from 2008 to 2011. Multivariable logistic regression analyses in all men and in 100 with favorable-risk PC addressed whether erMRI evidence of T3 disease was associated with prostatectomy T3 or Gleason score (GS) 8-10 (in patients with biopsy GS {<=}7) PC, adjusting for age, prostate-specific antigen level, clinical T category, biopsy GS, and percent positive biopsies. Results: The accuracy of erMRI prediction of extracapsular extension and seminal vesicle invasion was 75% and 95%, respectively. For all men, erMRI evidence of a T3 lesion versus T2 was associated with an increased odds of having pT3 disease (adjusted odds ratio [AOR] 4.81, 95% confidence interval [CI] 1.36-16.98, P=.015) and pGS 8-10 (AOR 5.56, 95% CI 1.10-28.18, P=.038). In the favorable-risk population, these results were AOR 4.14 (95% CI 1.03-16.56), P=.045 and AOR 7.71 (95% CI 1.36-43.62), P=.021, respectively. Conclusions: Three-Tesla multiparametric erMRI in men with favorable-risk PC provides information beyond that contained in known preoperative predictors about the presence of occult extraprostatic and/or high-grade PC. If validated in additional studies, this information can be used to counsel men planning to undergo radical prostatectomy or radiation therapy about the possible need for adjuvant radiation therapy or the utility of adding hormone therapy, respectively.

  13. Fifteen-Year Biochemical Relapse-Free Survival, Cause-Specific Survival, and Overall Survival Following I{sup 125} Prostate Brachytherapy in Clinically Localized Prostate Cancer: Seattle Experience

    SciTech Connect

    Sylvester, John E.; Grimm, Peter D.; Wong, Jason; Galbreath, Robert W.; Merrick, Gregory; Blasko, John C.

    2011-10-01

    Purpose: To report 15-year biochemical relapse-free survival (BRFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with I{sup 125} brachytherapy monotherapy for clinically localized prostate cancer early in the Seattle experience. Methods and Materials: Two hundred fifteen patients with clinically localized prostate cancer were consecutively treated from 1988 to 1992 with I{sup 125} monotherapy. They were prospectively followed as a tight cohort. They were evaluated for BRFS, CSS, and OS. Multivariate analysis was used to evaluate outcomes by pretreatment clinical prognostic factors. BRFS was analyzed by the Phoenix (nadir + 2 ng/mL) definition. CSS and OS were evaluated by chart review, death certificates, and referring physician follow-up notes. Gleason scoring was performed by general pathologists at a community hospital in Seattle. Time to biochemical failure (BF) was calculated and compared by Kaplan-Meier plots. Results: Fifteen-year BRFS for the entire cohort was 80.4%. BRFS by D'Amico risk group classification cohort analysis was 85.9%, 79.9%, and 62.2% for low, intermediate, and high-risk patients, respectively. Follow-up ranged from 3.6 to 18.4 years; median follow-up was 15.4 years for biochemically free of disease patients. Overall median follow-up was 11.7 years. The median time to BF in those who failed was 5.1 years. CSS was 84%. OS was 37.1%. Average age at time of treatment was 70 years. There was no significant difference in BRFS between low and intermediate risk groups. Conclusion: I{sup 125} monotherapy results in excellent 15-year BRFS and CSS, especially when taking into account the era of treatment effect.

  14. Statistical modeling and visualization of localized prostate cancer

    NASA Astrophysics Data System (ADS)

    Wang, Yue J.; Xuan, Jianhua; Sesterhenn, Isabell A.; Hayes, Wendelin S.; Ebert, David S.; Lynch, John H.; Mun, Seong K.

    1997-05-01

    In this paper, a statistically significant master model of localized prostate cancer is developed with pathologically- proven surgical specimens to spatially guide specific points in the biopsy technique for a higher rate of prostate cancer detection and the best possible representation of tumor grade and extension. Based on 200 surgical specimens of the prostates, we have developed a surface reconstruction technique to interactively visualize in the clinically significant objects of interest such as the prostate capsule, urethra, seminal vesicles, ejaculatory ducts and the different carcinomas, for each of these cases. In order to investigate the complex disease pattern including the tumor distribution, volume, and multicentricity, we created a statistically significant master model of localized prostate cancer by fusing these reconstructed computer models together, followed by a quantitative formulation of the 3D finite mixture distribution. Based on the reconstructed prostate capsule and internal structures, we have developed a technique to align all surgical specimens through elastic matching. By labeling the voxels of localized prostate cancer by '1' and the voxels of other internal structures by '0', we can generate a 3D binary image of the prostate that is simply a mutually exclusive random sampling of the underlying distribution f cancer to gram of localized prostate cancer characteristics. In order to quantify the key parameters such as distribution, multicentricity, and volume, we used a finite generalized Gaussian mixture to model the histogram, and estimate the parameter values through information theoretical criteria and a probabilistic self-organizing mixture. Utilizing minimally-immersive and stereoscopic interactive visualization, an augmented reality can be developed to allow the physician to virtually hold the master model in one hand and use the dominant hand to probe data values and perform a simulated needle biopsy. An adaptive self- organizing

  15. Simulated prostate biopsy: prostate cancer distribution and clinical correlation

    NASA Astrophysics Data System (ADS)

    Bauer, John J.; Zeng, Jianchao; Zhang, Wei; Sesterhenn, Isabell A.; Dean, Robert; Moul, Judd W.; Mun, Seong K.

    2000-04-01

    Our group has recently obtained data based upon whole- mounted step-sectioned radical prostatectomy specimens using a 3D computer assisted prostate biopsy simulator that suggests an increased detection rate is possible using laterally placed biopsies. A new 10-core biopsy pattern was demonstrated to be superior to the traditional sextant biopsy. This patter includes the traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland. The objective of this study is to confirm the higher prostate cancer defection rate obtained using our simulated 10-core biopsy pattern in a small clinical trial. We retrospectively reviewed 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. Of the 35 patients diagnosed with prostate cancer, 54.3 percent were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7 percent were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7 percent of patients were diagnosed solely with the laterally placed biopsies. Our results suggest that biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern.

  16. Hypofractionated Intensity-Modulated Radiotherapy (70 Gy at 2.5 Gy Per Fraction) for Localized Prostate Cancer: Cleveland Clinic Experience

    SciTech Connect

    Kupelian, Patrick A. . E-mail: patrick.kupelian@orhs.org; Willoughby, Twyla R.; Reddy, Chandana A.; Klein, Eric A.; Mahadevan, Arul

    2007-08-01

    Purpose: To study the outcomes in patients treated for localized prostate cancer with 70 Gy delivered at 2.5-Gy/fraction within 5 weeks. Methods and Materials: The study sample included all 770 consecutive patients with localized prostate cancer treated with hypofractionated intensity-modulated radiotherapy at the Cleveland Clinic between 1998 and 2005. The median follow-up was 45 months (maximum, 86). Both American Society for Therapeutic Radiology and Oncology (ASTRO) biochemical failure definition and the alternate nadir + 2 ng/mL definition were used. Results: The overall 5-year ASTRO biochemical relapse-free survival rate was 82% (95% confidence interval, 79-85%), and the 5-year nadir + 2 ng/mL rate was 83% (95% confidence interval, 79-86%). For patients with low-risk, intermediate-risk, and high-risk disease, the 5-year ASTRO rate was 95%, 85%, and 68%, respectively. The 5-year nadir + 2 ng/mL rate for patients with low-, intermediate-, and high-risk disease was 94%, 83%, and 72%, respectively. The Radiation Therapy Oncology Group acute rectal toxicity scores were 0 in 51%, 1 in 40%, and 2 in 9% of patients. The acute urinary toxicity scores were 0 in 33%, 1 in 48%, 2 in 18%, and 3 in 1% of patients. The late rectal toxicity scores were 0 in 89.6%, 1 in 5.9%, 2 in 3.1%, 3 in 1.3%, and 4 in 0.1% (1 patient). The late urinary toxicity scores were 0 in 90.5%, 1 in 4.3%, 2 in 5.1%, and 3 in 0.1% (1 patient). Conclusion: The outcomes after high-dose hypofractionation were acceptable in the entire cohort of patients treated with the schedule of 70 at 2.5 Gy/fraction.

  17. Ten-Year Outcomes: The Clinical Utility of Single Photon Emission Computed Tomography/Computed Tomography Capromab Pendetide (Prostascint) in a Cohort Diagnosed With Localized Prostate Cancer

    SciTech Connect

    Ellis, Rodney J.; Kaminsky, Deborah A.; Zhou, Esther H.; Fu, Pingfu; Chen, Wei-Dong; Faulhaber, Peter F.; Bodner, Donald

    2011-09-01

    Purpose: To evaluate the clinical utility of capromab pendetide imaging with single photon emission computed tomography coregistration with computed tomography (SPECT/CT) in primary prostate cancer (CaP) for pretreatment prognostic staging and localization of biologic target volumes (BTV) for individualized image-guided radiotherapy dose escalation (IGRT-DE). Methods and Materials: Patients consecutively presenting for primary radiotherapy (February 1997 to December 2002), having a clinical diagnosis of localized CaP, were evaluated for tumor stage using conventional staging and SPECT/CT (N = 239). Distant metastatic uptake (mets) were identified by SPECT/CT in 22 (9.2%). None of the suspected mets could be clinically confirmed. Thus, all subjects were followed without alteration in disease management. The SPECT/CT pelvic images defined BTV for IGRT-DE (+150% brachytherapy dose) without (n = 150) or with (n = 89) external radiation of 45 Gy. The National Comprehensive Cancer Network criteria defined risk groups (RG). The median survivor follow-up was 7 years. Biochemical disease-free survival (bDFS) was reported by clinical nadir +2 ng/mL (CN+2) criteria. Statistical analyses included Kaplan-Meier, multivariate analysis, and Concordance-index models. Results: At 10-year analyses, overall survival was 84.8% and bDFS was 84.6%. With stratification by RG, CN+2 bDFS was 93.5% for the low-RG (n = 116), 78.7% for the intermediate-RG (n = 94), and 68.8% for the high-RG (n = 29), p = 0.0002. With stratification by pretreatment SPECT/CT findings, bDFS was 65.5% in patients with suspected mets (n = 22) vs. 86.6% in patients with only localized uptake (n = 217), p = 0.0014. CaP disease-specific survival (DSS) was 97.7% for the cohort. With stratification by SPECT/CT findings, DSS was 86.4% (with suspected mets) vs. 99.0% (localized only), p = 0.0001. Using multivariate analysis, the DSS hazard ratio for SPECT/CT findings (mets vs. localized) was 3.58 (p = 0.0026). Concordance

  18. Gum arabic-coated radioactive gold nanoparticles cause no short-term local or systemic toxicity in the clinically relevant canine model of prostate cancer

    PubMed Central

    Axiak-Bechtel, Sandra M; Upendran, Anandhi; Lattimer, Jimmy C; Kelsey, James; Cutler, Cathy S; Selting, Kim A; Bryan, Jeffrey N; Henry, Carolyn J; Boote, Evan; Tate, Deborah J; Bryan, Margaret E; Katti, Kattesh V; Kannan, Raghuraman

    2014-01-01

    Introduction Gum arabic-coated radioactive gold nanoparticles (GA-198AuNPs) offer several advantages over traditional brachytherapy in the treatment of prostate cancer, including homogenous dose distribution and higher dose-rate irradiation. Our objective was to determine the short-term safety profile of GA-198AuNPs injected intralesionally. We proposed that a single treatment of GA-198AuNPs would be safe with minimal-to-no evidence of systemic or local toxicity. Methods Nine dogs with spontaneously occurring prostatic cancer were treated. Injections were performed with ultrasound or computerized tomography guidance. Complete blood counts, chemistry panels, and urinalyses were performed at weekly intervals for 1 month and imaging was repeated 4 weeks postinjection. Planar scintigraphic images were obtained within 30 minutes of injection. Results No statistically significant difference was found in any hematologic or biochemical parameter studied, nor was any evidence of tumor swelling or abscessation found in eight dogs with repeat imaging; one dog died secondary to urethral obstruction 12 days following injection. At 30 minutes postinjection, an average of 53% of injected dose in seven dogs was retained in the prostate, with loss of remaining activity in the bladder and urethra; no systemic uptake was detected. Conclusion GA-198AuNP therapy had no short-term toxicity in the treatment of prostatic cancer. While therapeutic agent was found in the prostate immediately following injection, some loss of agent was detected in the bladder and urethra. Localization of radioactivity within the prostate was lower than anticipated and likely due to normal vestigial prostatic ducts. Therefore, further study of retention, dosimetry, long-term toxicity, and efficacy of this treatment is warranted prior to Phase I trials in men. PMID:25378926

  19. Stereotactic Body Radiotherapy for Clinically Localized Prostate Cancer: Toxicity and Biochemical Disease-Free Outcomes from a Multi-Institutional Patient Registry

    PubMed Central

    Sharma, Sanjeev; Shumway, Richard; Perry, David; Bydder, Sean; Simpson, C. Kelley; D'Ambrosio, David

    2015-01-01

    Objectives: To report on initial patient characteristics, treatment practices, toxicity, and early biochemical disease-free survival (bDFS) of localized prostate cancer treated with stereotactic body radiotherapy (SBRT) and enrolled in the RSSearch® Patient Registry. Methods: A retrospective analysis was conducted on patients with clinically localized prostate cancer enrolled in RSSearch® from June 2006 - January 2015. Patients were classified as low-risk (PSA ≤ 10 ng/ml, T1c-T2a, Gleason score ≤ 6), intermediate-risk (PSA 10.1 - 20 ng/ml, T2b-T2c, or Gleason 7), or high-risk (PSA > 20 ng/ml, T3 or Gleason ≥ 8). Toxicity was reported using Common Toxicity Criteria for Adverse Events, version 3. Biochemical failure was assessed using the Phoenix definition (nadir + 2 ng/ml). The Kaplan-Meier analysis was used to calculate bDFS and association of patient and tumor characteristics with the use of SBRT. Results: Four hundred thirty-seven patients (189 low, 215 intermediate, and 33 high-risk) at a median of 69 years (range: 48-88) received SBRT at 17 centers. Seventy-eight percent of patients received 36.25 Gy/5 fractions, 13% received 37 Gy/5 fractions, 6% received 35 Gy/5 fractions, 3% received 38 Gy/4 fractions, and 5% received a boost dose of 19.5-29 Gy following external beam radiation therapy. Median follow-up was 20 months (range: 1–64 months). Genitourinary (GU) and gastrointestinal (GI) toxicities were minimal, with no acute or late Grade 3+ GU or GI toxicity. Late Grade 1 and 2 urinary frequency was 25% and 8%. Late Grade 1 and 2 proctitis was 3% and 2%. Median PSA decreased from 5.8 ng/ml (range: 0.3-43) to 0.88, 0.4, and 0.3 ng/ml at one, two, and three years. Two-year bDFS for all patients was 96.1%. Two-year bDFS was 99.0%, 94.5%, and 89.8% for low, intermediate, and high-risk patients (p < 0.0001). Two-year bDFS was 99.2%, 93.2%, and 90.4% for Gleason ≤ 6, Gleason 7, and Gleason ≥ 8 (p < 0.0001). Two-year bDFS was 96.4%, 97

  20. Outcomes in Localized Prostate Cancer: National Prostate Cancer Register of Sweden Follow-up Study

    PubMed Central

    Holmberg, Erik; Johansson, Jan-Erik; Holmberg, Lars; Adolfsson, Jan; Hugosson, Jonas

    2010-01-01

    Background Treatment for localized prostate cancer remains controversial. To our knowledge, there are no outcome studies from contemporary population-based cohorts that include data on stage, Gleason score, and serum levels of prostate-specific antigen (PSA). Methods In the National Prostate Cancer Register of Sweden Follow-up Study, a nationwide cohort, we identified 6849 patients aged 70 years or younger. Inclusion criteria were diagnosis with local clinical stage T1–2 prostate cancer from January 1, 1997, through December 31, 2002, a Gleason score of 7 or less, a serum PSA level of less than 20 ng/mL, and treatment with surveillance (including active surveillance and watchful waiting, n = 2021) or curative intent (including radical prostatectomy, n = 3399, and radiation therapy, n = 1429). Among the 6849 patients, 2686 had low-risk prostate cancer (ie, clinical stage T1, Gleason score 2-6, and serum PSA level of <10 ng/mL). The study cohort was linked to the Cause of Death Register, and cumulative incidence of death from prostate cancer and competing causes was calculated. Results For the combination of low- and intermediate-risk prostate cancers, calculated cumulative 10-year prostate cancer–specific mortality was 3.6% (95% confidence interval [CI] = 2.7% to 4.8%) in the surveillance group and 2.7% (95% CI = 2.1% to 3.45) in the curative intent group. For those with low-risk disease, the corresponding values were 2.4% (95% CI = 1.2% to 4.1%) among the 1085 patients in the surveillance group and 0.7% (95% CI = 0.3% to 1.4%) among the 1601 patients in the curative intent group. The 10-year risk of dying from competing causes was 19.2% (95% CI = 17.2% to 21.3%) in the surveillance group and 10.2% (95% CI = 9.0% to 11.4%) in the curative intent group. Conclusion A 10-year prostate cancer–specific mortality of 2.4% among patients with low-risk prostate cancer in the surveillance group indicates that surveillance may be a suitable treatment option for many

  1. Prospective evaluation of a hydrogel spacer for rectal separation in dose-escalated intensity-modulated radiotherapy for clinically localized prostate cancer

    PubMed Central

    2013-01-01

    Background As dose-escalation in prostate cancer radiotherapy improves cure rates, a major concern is rectal toxicity. We prospectively assessed an innovative approach of hydrogel injection between prostate and rectum to reduce the radiation dose to the rectum and thus side effects in dose-escalated prostate radiotherapy. Methods Acute toxicity and planning parameters were prospectively evaluated in patients with T1-2 N0 M0 prostate cancer receiving dose-escalated radiotherapy after injection of a hydrogel spacer. Before and after hydrogel injection, we performed MRI scans for anatomical assessment of rectal separation. Radiotherapy was planned and administered to 78 Gy in 39 fractions. Results From eleven patients scheduled for spacer injection the procedure could be performed in ten. In one patient hydrodissection of the Denonvillier space was not possible. Radiation treatment planning showed low rectal doses despite dose-escalation to the target. In accordance with this, acute rectal toxicity was mild without grade 2 events and there was complete resolution within four to twelve weeks. Conclusions This prospective study suggests that hydrogel injection is feasible and may prevent rectal toxicity in dose-escalated radiotherapy of prostate cancer. Further evaluation is necessary including the definition of patients who might benefit from this approach. Trial registration: German Clinical Trials Register DRKS00003273. PMID:23336502

  2. Benign Prostatic Hyperplasia: from Bench to Clinic

    PubMed Central

    Cho, Hee Ju

    2012-01-01

    Benign prostatic hyperplasia (BPH) is a prevalent disease, especially in old men, and often results in lower urinary tract symptoms (LUTS). This chronic disease has important care implications and financial risks to the health care system. LUTS are caused not only by mechanical prostatic obstruction but also by the dynamic component of obstruction. The exact etiology of BPH and its consequences, benign prostatic enlargement and benign prostatic obstruction, are not identified. Various theories concerning the causes of benign prostate enlargement and LUTS, such as metabolic syndrome, inflammation, growth factors, androgen receptor, epithelial-stromal interaction, and lifestyle, are discussed. Incomplete overlap of prostatic enlargement with symptoms and obstruction encourages focus on symptoms rather than prostate enlargement and the shifting from surgery to medicine as the treatment of BPH. Several alpha antagonists, including alfuzosin, doxazosin, tamsulosin, and terazosin, have shown excellent efficacy without severe adverse effects. In addition, new alpha antagonists, silodosin and naftopidil, and phosphodiesterase 5 inhibitors are emerging as BPH treatments. In surgical treatment, laser surgery such as photoselective vaporization of the prostate and holmium laser prostatectomy have been introduced to reduce complications and are used as alternatives to transurethral resection of the prostate (TURP) and open prostatectomy. The status of TURP as the gold standard treatment of BPH is still evolving. We review several preclinical and clinical studies about the etiology of BPH and treatment options. PMID:22468207

  3. A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Armstrong, John G.; Gillham, Charles M.; Dunne, Mary T.; Fitzpatrick, David A.; Finn, Marie A.; Cannon, Mairin E.; Taylor, Judy C.; O'Shea, Carmel M.; Buckney, Steven J.; Thirion, Pierre G.

    2011-09-01

    Purpose: To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer. Methods and Materials: Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng/mL, Gleason score {>=}7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival. Results: The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2. Conclusion: No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

  4. Prostate Cancer Prevention: Concepts and Clinical Trials.

    PubMed

    Hamilton, Zachary; Parsons, J Kellogg

    2016-04-01

    Prevention is an important treatment strategy for diminishing prostate cancer morbidity and mortality and is applicable to both early- and late-stage disease. There are three basic classifications of cancer prevention: primary (prevention of incident disease), secondary (identification and treatment of preclinical disease), and tertiary (prevention of progression or recurrence). Based on level I evidence, 5-alpha reductase inhibitors (5-ARIs) should be considered in selected men to prevent incident prostate cancer. Level I evidence also supports the consideration of dutasteride, a 5-ARI, for tertiary prevention in active surveillance and biochemical recurrence patients. Vitamins and supplements, including selenium or vitamin E, have not been proven in clinical trials to prevent prostate cancer and in the case of Vitamin E has been found to increase the risk of incident prostate cancer. Ongoing and future trials may further elucidate the role of diet and immunotherapy for prevention of prostate cancer. PMID:26957512

  5. Evaluating localized prostate cancer and identifying candidates for focal therapy.

    PubMed

    Sartor, A Oliver; Hricak, Hedvig; Wheeler, Thomas M; Coleman, Jonathan; Penson, David F; Carroll, Peter R; Rubin, Mark A; Scardino, Peter T

    2008-12-01

    accurate staging, grading, and tumor localization needed for a focal therapy program. Nevertheless, for men with minimal cancer who are amenable to active surveillance or focal therapy, consensus about the most accurate biopsy strategy has not yet been reached. Imaging, particularly magnetic resonance imaging and magnetic resonance spectroscopic imaging, has been used to assess men with early-stage prostate cancer. Large-volume cancers can be seen reasonably well, but small lesions have been difficult to detect reliably or measure accurately. Factors such as voxel resolution, organ movement, biopsy artifact, and benign changes have limited the consistent estimation of the quantitative tumor volume. Nevertheless, magnetic resonance imaging and magnetic resonance spectroscopic imaging can aid in evaluating patients with prostate cancer being considered for focal therapy by providing additional evidence that the patient does not harbor an otherwise undetected high-risk, aggressive cancer. In some cases, imaging can usefully identify the location of even a limited-sized index cancer. When imaging findings are substantiated by mapping biopsy results, confidence in the accurate characterization of the cancer is enhanced. Correlating the imaging results with tissue changes during and after treatment can be of use in monitoring the ablative effects in the prostate and in assessing for tumor recurrence. More work is necessary before staging studies can uniformly characterize a prostate cancer before therapy, much less reliably identify and locate small-volume cancer within the prostate. However, exploring the role of focal ablation as a therapeutic option for selected men with low-risk, clinically localized, prostate cancer need not await the emergence of perfectly accurate staging studies, any more than the application of radical surgery or radiotherapy have. Modern biopsy strategies, combined with optimal imaging and nomograms to estimate the pathologic stage and risk, taken

  6. Expression and Localization of Aquaporins in Benign Prostate Hyperplasia and Prostate Cancer

    PubMed Central

    Hwang, Insang; Hwang, Eu-Chang; Song, Seung Hee; Lee, Hyun-Suk; Kim, Sun-Ouck; Kang, Taek-Won; Kwon, Dongdeuk; Park, Kwangsung

    2012-01-01

    The aquaporin (AQP) families of water channels are intrinsic membrane proteins that facilitate selective water and small solute movement across the plasma membrane. The purposes of this study were to determine the expression and localization of AQPs in benign prostatic hyperplasia and prostate cancer. Prostatic tissue was collected from patients with benign prostatic hyperplasia or prostate cancer by transurethral resection of the prostate. The expression and cellular localization of the AQPs were determined in the human prostate by Western blot and immunohistochemistry. AQP1, 3, and 9 were expressed in the human prostate. Western blot analysis revealed bands at 28-36 kDa for the AQP1, 3, and 9 proteins. Of these proteins, AQP3 and 9 were expressed in the epithelium. Immunolabeling showed that AQP1 was mainly expressed in the capillaries and venules of the prostate, AQP9 was expressed in the cytoplasm of the epithelium, and AQP3 was mainly associated with the plasma membrane of the prostatic epithelium. Only AQP3 expression was localized in the cell membrane, and expressed AQP3 was translocated to the cytoplasm in prostate cancer. The epithelium in the human prostate expresses AQP3 and 9 proteins, and the capillaries and venules of the prostate express AQP1. Characterizing or modifying the expression of AQP3 may lead to an understanding of the role of the AQPs in human prostatic disease. PMID:23323224

  7. Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized disease: First clinical trial results

    SciTech Connect

    Madsen, Berit L. . E-mail: ronblm@vmmc.org; Hsi, R. Alex; Pham, Huong T.; Fowler, Jack F.; Esagui, Laura C.; Corman, John

    2007-03-15

    Purpose: To evaluate the feasibility and toxicity of stereotactic hypofractionated accurate radiotherapy (SHARP) for localized prostate cancer. Methods and Materials: A Phase I/II trial of SHARP performed for localized prostate cancer using 33.5 Gy in 5 fractions, calculated to be biologically equivalent to 78 Gy in 2 Gy fractions ({alpha}/{beta} ratio of 1.5 Gy). Noncoplanar conformal fields and daily stereotactic localization of implanted fiducials were used for treatment. Genitourinary (GU) and gastrointestinal (GI) toxicity were evaluated by American Urologic Association (AUA) score and Common Toxicity Criteria (CTC). Prostate-specific antigen (PSA) values and self-reported sexual function were recorded at specified follow-up intervals. Results: The study includes 40 patients. The median follow-up is 41 months (range, 21-60 months). Acute toxicity Grade 1-2 was 48.5% (GU) and 39% (GI); 1 acute Grade 3 GU toxicity. Late Grade 1-2 toxicity was 45% (GU) and 37% (GI). No late Grade 3 or higher toxicity was reported. Twenty-six patients reported potency before therapy; 6 (23%) have developed impotence. Median time to PSA nadir was 18 months with the majority of nadirs less than 1.0 ng/mL. The actuarial 48-month biochemical freedom from relapse is 70% for the American Society for Therapeutic Radiology and Oncology definition and 90% by the alternative nadir + 2 ng/mL failure definition. Conclusions: SHARP for localized prostate cancer is feasible with minimal acute or late toxicity. Dose escalation should be possible.

  8. A clinical review on extreme hypofractionated stereotactic body radiation therapy for localized prostate cancer using nonrobotic linear accelerators.

    PubMed

    Macias, Victor A; Perez-Romasanta, Luis A

    2014-06-01

    Seven phase I-II studies fell within the inclusion criteria. Details on the radiotherapy technique, patient selection, fractionation scheme, exclusion criteria, treatment toxicity, quality-of-life, and tumor control were collected. The studies provide encouraging results of acute and late toxicity, with rare grade 3 events, that seem comparable to robotic SBRT. The biochemical disease-free survival rates look promising, but most patients belong to the low-risk group. The trials are limited by a short follow-up, small number of patients, and different approaches in prescribing dose and defining the acceptable dose heterogeneities. Currently, nonrobotic SBRT regimens should be used in the context of clinical trials.

  9. [Prostate biopsy: Procedure in the clinical routine].

    PubMed

    Enzmann, T; Tokas, T; Korte, K; Ritter, M; Hammerer, P; Franzaring, L; Heynemann, H; Gottfried, H-W; Bertermann, H; Meyer-Schwickerath, M; Wirth, B; Pelzer, A; Loch, T

    2015-12-01

    Over the last decade there has been a 25% decrease in the mortality rates for prostate cancer. The reasons for this significant decrease are most likely associated with the application of urological screening tests. The main tools for early detection are currently increased public awareness of the disease, prostate-specific antigen (PSA) tests and transrectal ultrasound (TRUS) guided topographically assignable biopsy sampling. Together with the histopathological results these features provide essential information for risk stratification, diagnostics and therapy decisions. The evolution of prostate biopsy techniques as well as the use of PSA testing has led to an increased identification of asymptomatic men, where further clarification is necessary. Significant efforts and increased clinical research focus on determining the appropriate indications for a prostate biopsy and the optimal technique to achieve better detection rates. The most widely used imaging modality for the prostate is TRUS; however, there are no clearly defined standards for the clinical approach for each individual biopsy procedure, dealing with continuous technical optimization and in particular the developments in imaging. In this review the current principles, techniques, new approaches and instrumentation of prostate biopsy imaging control are presented within the framework of the structured educational approach. PMID:26704284

  10. Imaging Localized Prostate Cancer: Current Approaches and New Developments

    PubMed Central

    Turkbey, Baris; Albert, Paul S.; Kurdziel, Karen; Choyke, Peter L.

    2012-01-01

    OBJECTIVE Prostate cancer is the most common noncutaneous malignancy among men in the Western world. Imaging has recently become more important in the diagnosis, local staging, and treatment follow-up of prostate cancer. In this article, we review conventional and functional imaging methods as well as targeted imaging approaches with novel tracers used in the diagnosis and staging of prostate cancer. CONCLUSION Although prostate cancer is the second leading cause of cancer death in men, imaging of localized prostate cancer remains limited. Recent developments in imaging technologies, particularly MRI and PET, may lead to significant improvements in lesion detection and staging. PMID:19457807

  11. [Specific prostatic antigen in prostatic carcinoma: its relationship with tumor differentiation and clinical course].

    PubMed

    Sáenz de Chirife, A M; Bassi, A M; Celeste, F; Bergdolt, D

    1991-05-01

    Carcinoma of the prostate is a tumor with a variable clinical course and a high incidence of local progression and/or metastasis. This study was undertaken to evaluate tissue prostate specific antigen (PSA) in patients with carcinoma of the prostate, its correlation with Gleason's grading and its value in predicting the clinical course of these patients. We studied 28 transurethral biopsies of patients with prostatic carcinoma utilizing HE and peroxidase-antiperoxidase staining techniques. These were given a score of 2 to 10 using Gleason's grading. PSA was determined according to percent positivity. The clinical course was considered favourable (F) when the lesion remained stable and unfavourable (U) when peri-prostatic spread was evidenced, metastasis and/or death from the disease. Statistical analysis was performed with the linear discriminatory test. PSA percentages ranged from 0 to 95 and the Gleason score from 3 to 11. There was an indirect correlation between these methods (r = 0.74): high Gleason scores corresponded to low PSA values and viceversa. PSA was highly positive in patients with F and U clinical courses whereas low positive values (less than 40%) were observed only in patients with U clinical course. High Gleason (8 to 10) and low (less than 5) scores were observed only in patients with a clinical course of U or F, respectively, while intermediate values (5 to 8) were not predictive of the clinical course. Discriminatory analysis gave Z values of -2.446 (P = 0.014) for PSA, -2.90 (P = 0.004) for the Gleason score in predicting prognosis, conferring a greater value overall to the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Multigene Testing in Localized Prostate Cancer.

    PubMed

    Ross, Ashley E

    2016-05-01

    Currently, there are several commercially available multigene tests for risk stratification in prostate cancer. These tests have been validated retrospectively; however, prospective studies are needed to fully establish their clinical roles. In some cases, molecular studies may add value, and updated NCCN Guidelines recommend "consideration" of molecular tests under certain circumstances, such as to help ascertain the likelihood of death from conservative management, of biochemical progression after radical prostatectomy or external-beam therapy, and of developing metastasis after radical prostatectomy or salvage radiotherapy.

  13. Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland.

    PubMed

    Seeram, Navindra P; Aronson, William J; Zhang, Yanjun; Henning, Susanne M; Moro, Aune; Lee, Ru-Po; Sartippour, Maryam; Harris, Diane M; Rettig, Matthew; Suchard, Marc A; Pantuck, Allan J; Belldegrun, Arie; Heber, David

    2007-09-19

    Our group has shown in a phase II clinical trial that pomegranate juice (PJ) increases prostate specific antigen (PSA) doubling time in prostate cancer (CaP) patients with a rising PSA. Ellagitannins (ETs) are the most abundant polyphenols present in PJ and contribute greatly towards its reported biological properties. On consumption, ETs hydrolyze to release ellagic acid (EA), which is then converted by gut microflora to 3,8-dihydroxy-6H-dibenzo[b, d]pyran-6-one (urolithin A, UA) derivatives. Despite the accumulating knowledge of ET metabolism in animals and humans, there is no available data on the pharmacokinetics and tissue disposition of urolithins. Using a standardized ET-enriched pomegranate extract (PE), we sought to further define the metabolism and tissue distribution of ET metabolites. PE and UA (synthesized in our laboratory) were administered to C57BL/6 wild-type male mice, and metabolite levels in plasma and tissues were determined over 24 h. ET metabolites were concentrated at higher levels in mouse prostate, colon, and intestinal tissues as compared to other tissues after administration of PE or UA. We also evaluated the effects of PE on CaP growth in severe combined immunodeficient (SCID) mice injected subcutaneously with human CaP cells (LAPC-4). PE significantly inhibited LAPC-4 xenograft growth in SCID mice as compared to vehicle control. Finally, EA and several synthesized urolithins were shown to inhibit the growth of human CaP cells in vitro. The chemopreventive potential of pomegranate ETs and localization of their bioactive metabolites in mouse prostate tissue suggest that pomegranate may play a role in CaP treatment and chemoprevention. This warrants future human tissue bioavailability studies and further clinical studies in men with CaP.

  14. Virtual HDR{sup SM} CyberKnife Treatment for Localized Prostatic Carcinoma: Dosimetry Comparison With HDR Brachytherapy and Preliminary Clinical Observations

    SciTech Connect

    Fuller, Donald B. Naitoh, John; Lee, Charles; Hardy, Steven C.; Jin, Haoran

    2008-04-01

    Background: We tested our ability to approximate the dose (38 Gy), fractionation (four fractions), and distribution of high-dose-rate (HDR) brachytherapy for prostate cancer with CyberKnife (CK) stereotactic body radiotherapy (SBRT) plans. We also report early clinical observations of CK SBRT treatment. Methods and Materials: Ten patients were treated with CK. For each CK SBRT plan, an HDR plan was designed using common contour sets and simulated HDR catheters. Planning target volume coverage, intraprostatic dose escalation, and urethra, rectum, and bladder exposure were compared. Results: Planning target volume coverage by the prescription dose was similar for CK SBRT and HDR plans, whereas percent of volume of interest receiving 125% of prescribed radiation dose (V125) and V150 values were higher for HDR, reflecting higher doses near HDR source dwell positions. Urethra dose comparisons were lower for CK SBRT in 9 of 10 cases, suggesting that CK SBRT may more effectively limit urethra dose. Bladder maximum point doses were higher with HDR, but bladder dose falloff beyond the maximum dose region was more rapid with HDR. Maximum rectal wall doses were similar, but CK SBRT created sharper rectal dose falloff beyond the maximum dose region. Second CK SBRT plans, constructed by equating urethra radiation dose received by point of maximum exposure of volume of interest to the HDR plan, significantly increased V125 and V150. Clinically, 4-month post-CK SBRT median prostate-specific antigen levels decreased 86% from baseline. Acute toxicity was primarily urologic and returned to baseline by 2 months. Acute rectal morbidity was minimal and transient. Conclusions: It is possible to construct CK SBRT plans that closely recapitulate HDR dosimetry and deliver the plans noninvasively.

  15. Formalized prediction of clinically significant prostate cancer: is it possible?

    PubMed Central

    Nguyen, Carvell T; Kattan, Michael W

    2012-01-01

    Greater understanding of the biology and epidemiology of prostate cancer in the last several decades have led to significant advances in its management. Prostate cancer is now detected in greater numbers at lower stages of disease and is amenable to multiple forms of efficacious treatment. However, there is a lack of conclusive data demonstrating a definitive mortality benefit from this earlier diagnosis and treatment of prostate cancer. It is likely due to the treatment of a large proportion of indolent cancers that would have had little adverse impact on health or lifespan if left alone. Due to this overtreatment phenomenon, active surveillance with delayed intervention is gaining traction as a viable management approach in contemporary practice. The ability to distinguish clinically insignificant cancers from those with a high risk of progression and/or lethality is critical to the appropriate selection of patients for surveillance protocols versus immediate intervention. This chapter will review the ability of various prediction models, including risk groupings and nomograms, to predict indolent disease and determine their role in the contemporary management of clinically localized prostate cancer. PMID:22367181

  16. 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.

  17. Final Report of Multicenter Canadian Phase III Randomized Trial of 3 Versus 8 Months of Neoadjuvant Androgen Deprivation Therapy Before Conventional-Dose Radiotherapy for Clinically Localized Prostate Cancer

    SciTech Connect

    Crook, Juanita Ludgate, Charles; Malone, Shawn; Perry, Gad; Eapen, Libni; Bowen, Julie; Robertson, Susan; Lockwood, Gina M.Math.

    2009-02-01

    Purpose: To evaluate the effect of 3 vs. 8 months of neoadjuvant hormonal therapy before conventional-dose radiotherapy (RT) on disease-free survival for localized prostate cancer. Methods and Materials: Between February 1995 and June 2001, 378 men were randomized to either 3 or 8 months of flutamide and goserelin before 66 Gy RT at four participating centers. The median baseline prostate-specific antigen level was 9.7 ng/mL (range, 1.3-189). Of the 378 men, 26% had low-, 43% intermediate-, and 31% high-risk disease. The two arms were balanced in terms of age, Gleason score, clinical T category, risk group, and presenting prostate-specific antigen level. The median follow-up for living patients was 6.6 years (range, 1.6-10.1). Of the 378 patients, 361 were evaluable, and 290 were still living. Results: The 5-year actuarial freedom from failure rate for the 3- vs. 8-month arms was 72% vs. 75%, respectively (p = 0.18). No difference was found in the failure types between the two arms. The median prostate-specific antigen level at the last follow-up visit for patients without treatment failure was 0.6 ng/mL in the 3-month arm vs. 0.50 ng/mL in the 8-month arm. The disease-free survival rate at 5 years was improved for the high-risk patients in the 8-month arm (71% vs. 42%, p = 0.01). Conclusion: A longer period of NHT before standard-dose RT did not alter the patterns of failure when combined with 66-Gy RT. High-risk patients in the 8-month arm had significant improvement in the 5-year disease-free survival rate.

  18. Prostate cancer epigenetics and its clinical implications

    PubMed Central

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy. PMID:27212125

  19. Radiation With or Without 6 Months of Androgen Suppression Therapy in Intermediate- and High-Risk Clinically Localized Prostate Cancer: A Postrandomization Analysis by Risk Group

    SciTech Connect

    Nguyen, Paul L.; Chen, Ming-Hui; Beard, Clair J.; Suh, W. Warren

    2010-07-15

    Purpose: Six months of androgen suppression therapy (AST) plus radiation (RT) prolongs survival vs. RT alone in men with unfavorable risk localized prostate cancer (PCa), but it is unknown if this benefit applies to all risk subgroups and, in particular, the intermediate-risk group. Methods and Materials: Among 206 men with stages T1b to T2b PCa and either a prostate-specific antigen level of >10 or a Gleason score of {>=}7 or MRI evidence of T3 disease randomized to receive 70 Gy of RT with or without 6 months of AST, Cox multivariable analysis was used to assess the impact of AST on overall survival in intermediate- and high-risk localized PCa, adjusting for age, Adult Comorbidity Evaluation 27 comorbidity score, interaction between comorbidity and treatment, and known prognostic factors. Survival estimates were compared using a two-sided log-rank test. Results: After an 8.2-year median follow-up, 74 men died. Compared to treatment with AST plus RT, treatment with RT alone was associated with an increased risk of death in intermediate-risk (adjusted hazard ratio, 3.0 [95% confidence interval, 1.3-7.2]; p = 0.01) and high-risk PCa (adjusted hazard ratio, 3.3 [95% confidence interval, 0.94-11.3]; p = 0.06). The survival benefit of adding AST was restricted to men with no or mild comorbidity in both the intermediate-risk (90.9% vs. 85.8% survival, respectively, at 7 years for AST plus RT vs. RT alone; p = 0.009) and high-risk (88.9% vs. 51.2% survival, respectively, at 7 years for AST plus RT vs. RT alone; p = 0.007) subgroups. Conclusions: In men with localized PCa who have no or mild comorbidity, adding 6 months of AST to RT was associated with improved survival for those with both intermediate-risk and high-risk disease, but in men with moderate to severe comorbidity, no benefit was observed in either risk group.

  20. Is Biochemical Response More Important Than Duration of Neoadjuvant Hormone Therapy Before Radiotherapy for Clinically Localized Prostate Cancer? An Analysis of the 3- Versus 8-Month Randomized Trial

    SciTech Connect

    Alexander, Abraham; Crook, Juanita; Jones, Stuart; Malone, Shawn; Bowen, Julie; Truong, Pauline; Pai, Howard; Ludgate, Charles

    2010-01-15

    Purpose: To ascertain whether biochemical response to neoadjuvant androgen-deprivation therapy (ADT) before radiotherapy (RT), rather than duration, is the critical determinant of benefit in the multimodal treatment of localized prostate cancer, by comparing outcomes of subjects from the Canadian multicenter 3- vs 8-month trial with a pre-RT, post-hormone PSA (PRPH-PSA) <=0.1 ng/ml vs those >0.1 ng/ml. Methods and Materials: From 1995 to 2001, 378 men with localized prostate cancer were randomized to 3 or 8 months of neoadjuvant ADT before RT. On univariate analysis, survival indices were compared between those with a PRPH-PSA <=0.1 ng/ml vs >0.1 ng/ml, for all patients and subgroups, including treatment arm, risk group, and gleason Score. Multivariate analysis identified independent predictors of outcome. Results: Biochemical disease-free survival (bDFS) was significantly higher for those with a PRPH-PSA <=0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (55.3% vs 49.4%, p = 0.014). No difference in survival indices was observed between treatment arms. There was no difference in bDFS between patients in the 3- and 8-month arms with a PRPH-PSA <=0.1 ng/ml nor those with PRPH-PSA >0.1 ng/ml. bDFS was significantly higher for high-risk patients with PRPH-PSA <=0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (57.0% vs 29.4%, p = 0.017). Multivariate analysis identified PRPH-PSA (p = 0.041), Gleason score (p = 0.001), initial PSA (p = 0.025), and T-stage (p = 0.003), not ADT duration, as independent predictors of outcome. Conclusion: Biochemical response to neoadjuvant ADT before RT, not duration, appears to be the critical determinant of benefit in the setting of combined therapy. Individually tailored ADT duration based on PRPH-PSA would maximize therapeutic gain, while minimizing the duration of ADT and its related toxicities.

  1. Spatial genomic heterogeneity within localized, multifocal prostate cancer.

    PubMed

    Boutros, Paul C; Fraser, Michael; Harding, Nicholas J; de Borja, Richard; Trudel, Dominique; Lalonde, Emilie; Meng, Alice; Hennings-Yeomans, Pablo H; McPherson, Andrew; Sabelnykova, Veronica Y; Zia, Amin; Fox, Natalie S; Livingstone, Julie; Shiah, Yu-Jia; Wang, Jianxin; Beck, Timothy A; Have, Cherry L; Chong, Taryne; Sam, Michelle; Johns, Jeremy; Timms, Lee; Buchner, Nicholas; Wong, Ada; Watson, John D; Simmons, Trent T; P'ng, Christine; Zafarana, Gaetano; Nguyen, Francis; Luo, Xuemei; Chu, Kenneth C; Prokopec, Stephenie D; Sykes, Jenna; Dal Pra, Alan; Berlin, Alejandro; Brown, Andrew; Chan-Seng-Yue, Michelle A; Yousif, Fouad; Denroche, Robert E; Chong, Lauren C; Chen, Gregory M; Jung, Esther; Fung, Clement; Starmans, Maud H W; Chen, Hanbo; Govind, Shaylan K; Hawley, James; D'Costa, Alister; Pintilie, Melania; Waggott, Daryl; Hach, Faraz; Lambin, Philippe; Muthuswamy, Lakshmi B; Cooper, Colin; Eeles, Rosalind; Neal, David; Tetu, Bernard; Sahinalp, Cenk; Stein, Lincoln D; Fleshner, Neil; Shah, Sohrab P; Collins, Colin C; Hudson, Thomas J; McPherson, John D; van der Kwast, Theodorus; Bristow, Robert G

    2015-07-01

    Herein we provide a detailed molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer to delineate new oncogenes or tumor suppressors. We initially determined the copy number aberration (CNA) profiles of 74 patients with index tumors of Gleason score 7. Of these, 5 patients were subjected to whole-genome sequencing using DNA quantities achievable in diagnostic biopsies, with detailed spatial sampling of 23 distinct tumor regions to assess intraprostatic heterogeneity in focal genomics. Multifocal tumors are highly heterogeneous for single-nucleotide variants (SNVs), CNAs and genomic rearrangements. We identified and validated a new recurrent amplification of MYCL, which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation. Moreover, we demonstrate divergent tumor evolution in multifocal cancer and, in some cases, tumors of independent clonal origin. These data represent the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome and inform the development of novel biomarkers that reflect individual prognosis.

  2. Benign prostatic hyperplasia: clinical manifestations and evaluation.

    PubMed

    Santos Dias, José

    2012-12-01

    Benign prostatic hyperplasia (BPH) is a very common condition, related to aging and causing symptoms, called lower urinary tract symptoms. On account of its huge prevalence, it is important for clinicians who are involved in the management of patients with BPH to be aware of the very strict recommendations for BPH evaluation. In this article, we describe the different steps and procedures doctors should follow to evaluate these patients; symptoms and signs of BPH are reviewed, as well as the clinical evaluation steps and examinations available. The basic evaluation of the patients with BPH should include, according to the recommendations of the most relevant international guidelines, lower urinary tract symptoms evaluation with appropriate symptom scores, digital rectal examination, voiding charts, prostate-specific antigen and creatinine measurement, urinalysis, and imaging of the urinary tract.

  3. Prostate segmentation with local binary patterns guided active appearance models

    NASA Astrophysics Data System (ADS)

    Ghose, Soumya; Oliver, Arnau; Martí, Robert; Lladó, Xavier; Freixenet, Jordi; Vilanova, Joan C.; Meriaudeau, Fabrice

    2011-03-01

    Real-time fusion of Magnetic Resonance (MR) and Trans Rectal Ultra Sound (TRUS) images aid in the localization of malignant tissues in TRUS guided prostate biopsy. Registration performed on segmented contours of the prostate reduces computational complexity and improves the multimodal registration accuracy. However, accurate and computationally efficient segmentation of the prostate in TRUS images could be challenging in the presence of heterogeneous intensity distribution inside the prostate gland, and other imaging artifacts like speckle noise, shadow regions and low Signal to Noise Ratio (SNR). In this work, we propose to enhance the texture features of the prostate region using Local Binary Patterns (LBP) for the propagation of a shape and appearance based statistical model to segment the prostate in a multi-resolution framework. A parametric model of the propagating contour is derived from Principal Component Analysis (PCA) of the prior shape and texture information of the prostate from the training data. The estimated parameters are then modified with the prior knowledge of the optimization space to achieve an optimal segmentation. The proposed method achieves a mean Dice Similarity Coefficient (DSC) value of 0.94+/-0.01 and a mean segmentation time of 0.68+/-0.02 seconds when validated with 70 TRUS images of 7 datasets in a leave-one-patient-out validation framework. Our method performs computationally efficient and accurate prostate segmentation in the presence of intensity heterogeneities and imaging artifacts.

  4. Body Mass Index and Prostate-Specific Antigen Failure Following Brachytherapy for Localized Prostate Cancer

    SciTech Connect

    Efstathiou, Jason A. Skowronski, Rafi Y.; Coen, John J.; Grocela, Joseph A.; Hirsch, Ariel E.; Zietman, Anthony L.

    2008-08-01

    Purpose: Increasing body mass index (BMI) is associated with prostate-specific antigen (PSA) failure after radical prostatectomy and external beam radiation therapy (EBRT). We investigated whether BMI is associated with PSA failure in men treated with brachytherapy for clinically localized prostate cancer. Patients and Methods: Retrospective analyses were conducted on 374 patients undergoing brachytherapy for stage T1c-T2cNXM0 prostate cancer from 1996-2001. Forty-nine patients (13%) received supplemental EBRT and 131 (35%) received androgen deprivation therapy (ADT). Height and weight data were available for 353 (94%). Cox regression analyses were performed to evaluate the relationship between BMI and PSA failure (nadir + 2 ng/ml definition). Covariates included age, race, preimplantation PSA, Gleason score, T category, percent of prescription dose to 90% of the prostate, use of supplemental EBRT, and ADT. Results: Median age, PSA, and BMI were 66 years (range, 42-80 years), 5.7 ng/ml (range, 0.4-22.6 ng/ml), and 27.1 kg/m{sup 2} (range, 18.2-53.6 kg/m{sup 2}), respectively. After a median follow-up of 6.0 years (range, 3.0-10.2 years), there were 76 PSA recurrences. The BMI was not associated with PSA failure. Six-year PSA failure rates were 30.2% for men with BMI less than 25 kg/m{sup 2}, 19.5% for BMI of 25 or greater to less than 30 kg/m{sup 2}, and 14.4% for BMI of 30 kg/m{sup 2} or greater (p = 0.19). Results were similar when BMI was analyzed as a continuous variable, using alternative definitions of PSA failure, and excluding patients treated with EBRT and/or ADT. In multivariate analyses, only baseline PSA was significantly associated with shorter time to PSA failure (adjusted hazard ratio, 1.12; 95% confidence interval, 1.05-1.20; p 0.0006). Conclusions: Unlike after surgery or EBRT, BMI is not associated with PSA failure in men treated with brachytherapy for prostate cancer. This raises the possibility that brachytherapy may be a preferred treatment

  5. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: Recommendations of the RTOG-ASTRO Phoenix Consensus Conference

    SciTech Connect

    Roach, Mack . E-mail: roach@radonc17.ucsf.edu; Hanks, Gerald; Thames, Howard; Schellhammer, Paul; Shipley, William U.; Sokol, Gerald H.; Sandler, Howard

    2006-07-15

    In 1996 the American Society for Therapeutic Radiology and Oncology (ASTRO) sponsored a Consensus Conference to establish a definition of biochemical failure after external beam radiotherapy (EBRT). The ASTRO definition defined prostate specific antigen (PSA) failure as occurring after three consecutive PSA rises after a nadir with the date of failure as the point halfway between the nadir date and the first rise or any rise great enough to provoke initiation of therapy. This definition was not linked to clinical progression or survival; it performed poorly in patients undergoing hormonal therapy (HT), and backdating biased the Kaplan-Meier estimates of event-free survival. A second Consensus Conference was sponsored by ASTRO and the Radiation Therapy Oncology Group in Phoenix, Arizona, on January 21, 2005, to revise the ASTRO definition. The panel recommended: (1) a rise by 2 ng/mL or more above the nadir PSA be considered the standard definition for biochemical failure after EBRT with or without HT; (2) the date of failure be determined 'at call' (not backdated). They recommended that investigators be allowed to use the ASTRO Consensus Definition after EBRT alone (no hormonal therapy) with strict adherence to guidelines as to 'adequate follow-up.' To avoid the artifacts resulting from short follow-up, the reported date of control should be listed as 2 years short of the median follow-up. For example, if the median follow-up is 5 years, control rates at 3 years should be cited. Retaining a strict version of the ASTRO definition would allow comparisons with a large existing body of literature.

  6. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference.

    PubMed

    Roach, Mack; Hanks, Gerald; Thames, Howard; Schellhammer, Paul; Shipley, William U; Sokol, Gerald H; Sandler, Howard

    2006-07-15

    In 1996 the American Society for Therapeutic Radiology and Oncology (ASTRO) sponsored a Consensus Conference to establish a definition of biochemical failure after external beam radiotherapy (EBRT). The ASTRO definition defined prostate specific antigen (PSA) failure as occurring after three consecutive PSA rises after a nadir with the date of failure as the point halfway between the nadir date and the first rise or any rise great enough to provoke initiation of therapy. This definition was not linked to clinical progression or survival; it performed poorly in patients undergoing hormonal therapy (HT), and backdating biased the Kaplan-Meier estimates of event-free survival. A second Consensus Conference was sponsored by ASTRO and the Radiation Therapy Oncology Group in Phoenix, Arizona, on January 21, 2005, to revise the ASTRO definition. The panel recommended: (1) a rise by 2 ng/mL or more above the nadir PSA be considered the standard definition for biochemical failure after EBRT with or without HT; (2) the date of failure be determined "at call" (not backdated). They recommended that investigators be allowed to use the ASTRO Consensus Definition after EBRT alone (no hormonal therapy) with strict adherence to guidelines as to "adequate follow-up." To avoid the artifacts resulting from short follow-up, the reported date of control should be listed as 2 years short of the median follow-up. For example, if the median follow-up is 5 years, control rates at 3 years should be cited. Retaining a strict version of the ASTRO definition would allow comparisons with a large existing body of literature.

  7. Late rectal complications after prostate brachytherapy for localized prostate cancer: incidence and management.

    PubMed

    Phan, Jack; Swanson, David A; Levy, Lawrence B; Kudchadker, Rajat J; Bruno, Teresa L; Frank, Steven J

    2009-05-01

    This review of the literature on late rectal complications after prostate brachytherapy indicated that it is a highly effective treatment modality for patients with clinically localized prostate cancer but can cause chronic radiation proctitis. The most common manifestation of chronic radiation proctitis was anterior rectal wall bleeding, which often occurred within the first 2 years after brachytherapy. It is interesting to note that the rates of late rectal morbidity appear to have declined over time, which may reflect improvements in implantation techniques and imaging. Rectal biopsy as part of the workup to evaluate rectal bleeding can lead to rectal fistula and the need for colostomy, a rare but major complication. The authors recommend 1) screening colonoscopy before brachytherapy for patients who have not had a screening colonoscopy within the preceding 3 years to rule out colorectal malignancies and, thus, facilitate conservative management should rectal bleeding occur; 2) lifestyle modifications during treatment to limit exposure of the rectum to radiation; and 3) conservative management for rectal bleeding that occurs within 2 years after brachytherapy. Cancer 2009. (c) 2009 American Cancer Society.

  8. Early Quality of Life in Patients with Localized Prostate Carcinoma

    PubMed Central

    Eton, David T.; Lepore, Stephen J.; Helgeson, Vicki S.

    2008-01-01

    BACKGROUND Men with localized prostate carcinoma are faced with important treatment decisions, and quality of life (QoL) information has become a crucial element of decision making. The first objective of this study was to compare the early, health-related QoL (HRQoL) of men with localized prostate carcinoma who were treated with radical prostatectomy, external beam radiotherapy, or brachytherapy. A second objective was to identify demographic and psychosocial variables that predict HRQoL. METHODS Two-hundred fifty-six men with localized prostate carcinoma were interviewed within 7 weeks of treatment initiation. The interview included measures of prostate-specific HRQoL (the University of California—Los Angeles Prostate Cancer Index), general HRQoL (the SF-36), and psychosocial variables. RESULTS After adjusting for covariates, treatment group differences were found for both prostate specific HRQoL and general HRQoL. Men who underwent prostatectomy reported more urinary and sexual problems and more general physical dysfunction compared with men who were treated with either form of radiation therapy. Men who were treated with brachytherapy reported the fewest problems in sexual function and the least general physical dysfunction. Few treatment group differences were found in mental functioning. Both demographic factors and psychosocial factors predicted HRQoL. Older men and African-American men reported more physical problems than younger men and Caucasian men, respectively. A supportive social environment, high self-efficacy, and high self-esteem were predictive of better HRQoL. CONCLUSIONS Shortly after undergoing treatment for localized prostate carcinoma, men who underwent radical prostatectomy, older men, and African-American men are at heightened risk for experiencing prostate-specific and general deficits in HRQoL. Having psychosocial resources from which to draw may enhance HRQoL. PMID:11745222

  9. Clinical Experience With Gene Therapy for the Treatment of Prostate Cancer

    PubMed Central

    Stanizzi, Matthew A; Hall, Simon J

    2007-01-01

    Localized prostate cancer can be treated effectively with radical prostatectomy or radiation therapy. The treatment options for metastatic prostate cancer are limited to hormonal therapy; hormone-refractory cancer is treated with taxane-based chemotherapy, which provides only a modest survival benefit. New treatments are needed. The gene for the initiation of prostate cancer has not been identified; however, gene therapy can involve tumor injection of a gene to kill cells, systemic gene delivery to target and kill metastases, or local gene expression intended to generate a systemic response. This review will provide an overview of the various strategies of cancer gene therapy, focusing on those that have gone to clinical trial, detailing clinical experience in prostate cancer patients. PMID:17387369

  10. Therapeutic Strategies for Localized Prostate Cancer

    PubMed Central

    Lynch, John H; Batuello, Joseph T; Crawford, E David; Gomella, Leonard G; Kaufman, Joel; Petrylak, Daniel P; Joel, Andrew B

    2001-01-01

    Prostate-specific antigen determinations for prostate cancer screening have led to a dramatic increase in the number of men who are diagnosed with organ-confined and therefore potentially curable prostate cancer. Advances in predicting outcomes with artificial neural networks may help to recommend one therapy over another. Less invasive forms of treatment, such as high-intensity focused ultrasound, may ultimately give patients additional options for treatment. Furthermore, attempts to better define the role of both neoadjuvant hormonal therapy and chemotherapy may give higher-risk patients better outcomes than with current treatments. These advances as well as continued research will likely lead to a day when more and more men with organ-confined disease will be cured. PMID:16985999

  11. miRNA Expression Analyses in Prostate Cancer Clinical Tissues

    PubMed Central

    Bucay, Nathan; Shahryari, Varahram; Majid, Shahana; Yamamura, Soichiro; Mitsui, Yozo; Tabatabai, Z. Laura; Greene, Kirsten; Deng, Guoren; Dahiya, Rajvir; Tanaka, Yuichiro; Saini, Sharanjot

    2015-01-01

    A critical challenge in prostate cancer (PCa) clinical management is posed by the inadequacy of currently used biomarkers for disease screening, diagnosis, prognosis and treatment. In recent years, microRNAs (miRNAs) have emerged as promising alternate biomarkers for prostate cancer diagnosis and prognosis. However, the development of miRNAs as effective biomarkers for prostate cancer heavily relies on their accurate detection in clinical tissues. miRNA analyses in prostate cancer clinical specimens is often challenging owing to tumor heterogeneity, sampling errors, stromal contamination etc. The goal of this article is to describe a simplified workflow for miRNA analyses in archived FFPE or fresh frozen prostate cancer clinical specimens using a combination of quantitative real-time PCR (RT-PCR) and in situ hybridization (ISH). Within this workflow, we optimize the existing methodologies for miRNA extraction from FFPE and frozen prostate tissues and expression analyses by Taqman-probe based miRNA RT-PCR. In addition, we describe an optimized method for ISH analyses formiRNA detection in prostate tissues using locked nucleic acid (LNA)- based probes. Our optimized miRNA ISH protocol can be applied to prostate cancer tissue slides or prostate cancer tissue microarrays (TMA). PMID:26382040

  12. miRNA Expression Analyses in Prostate Cancer Clinical Tissues.

    PubMed

    Bucay, Nathan; Shahryari, Varahram; Majid, Shahana; Yamamura, Soichiro; Mitsui, Yozo; Tabatabai, Z Laura; Greene, Kirsten; Deng, Guoren; Dahiya, Rajvir; Tanaka, Yuichiro; Saini, Sharanjot

    2015-01-01

    A critical challenge in prostate cancer (PCa) clinical management is posed by the inadequacy of currently used biomarkers for disease screening, diagnosis, prognosis and treatment. In recent years, microRNAs (miRNAs) have emerged as promising alternate biomarkers for prostate cancer diagnosis and prognosis. However, the development of miRNAs as effective biomarkers for prostate cancer heavily relies on their accurate detection in clinical tissues. miRNA analyses in prostate cancer clinical specimens is often challenging owing to tumor heterogeneity, sampling errors, stromal contamination etc. The goal of this article is to describe a simplified workflow for miRNA analyses in archived FFPE or fresh frozen prostate cancer clinical specimens using a combination of quantitative real-time PCR (RT-PCR) and in situ hybridization (ISH). Within this workflow, we optimize the existing methodologies for miRNA extraction from FFPE and frozen prostate tissues and expression analyses by Taqman-probe based miRNA RT-PCR. In addition, we describe an optimized method for ISH analyses formiRNA detection in prostate tissues using locked nucleic acid (LNA)- based probes. Our optimized miRNA ISH protocol can be applied to prostate cancer tissue slides or prostate cancer tissue microarrays (TMA). PMID:26382040

  13. miRNA Expression Analyses in Prostate Cancer Clinical Tissues.

    PubMed

    Bucay, Nathan; Shahryari, Varahram; Majid, Shahana; Yamamura, Soichiro; Mitsui, Yozo; Tabatabai, Z Laura; Greene, Kirsten; Deng, Guoren; Dahiya, Rajvir; Tanaka, Yuichiro; Saini, Sharanjot

    2015-09-08

    A critical challenge in prostate cancer (PCa) clinical management is posed by the inadequacy of currently used biomarkers for disease screening, diagnosis, prognosis and treatment. In recent years, microRNAs (miRNAs) have emerged as promising alternate biomarkers for prostate cancer diagnosis and prognosis. However, the development of miRNAs as effective biomarkers for prostate cancer heavily relies on their accurate detection in clinical tissues. miRNA analyses in prostate cancer clinical specimens is often challenging owing to tumor heterogeneity, sampling errors, stromal contamination etc. The goal of this article is to describe a simplified workflow for miRNA analyses in archived FFPE or fresh frozen prostate cancer clinical specimens using a combination of quantitative real-time PCR (RT-PCR) and in situ hybridization (ISH). Within this workflow, we optimize the existing methodologies for miRNA extraction from FFPE and frozen prostate tissues and expression analyses by Taqman-probe based miRNA RT-PCR. In addition, we describe an optimized method for ISH analyses formiRNA detection in prostate tissues using locked nucleic acid (LNA)- based probes. Our optimized miRNA ISH protocol can be applied to prostate cancer tissue slides or prostate cancer tissue microarrays (TMA).

  14. Challenges in Clinical Prostate Cancer: Role of Imaging

    PubMed Central

    Kelloff, Gary J.; Choyke, Peter; Coffey, Donald S.

    2010-01-01

    Objective This article reviews a recent 2-day workshop on prostate cancer and imaging technology that was conducted by the Cancer Imaging Program of the National Cancer Institute. The workshop dealt with research trends and avenues for improving imaging and applications across the clinical spectrum of the disease. Conclusion After a summary of prostate cancer incidence and mortality, four main clinical challenges in prostate cancer treatment and management—diagnostic accuracy; risk stratification, initial staging, active surveillance, and focal therapy; prostate-specific antigen relapse after radiation therapy or radical prostatectomy; and assessing response to therapy in advanced disease—were discussed by the 55-member panel. The overarching issue in prostate cancer is distinguishing lethal from nonlethal disease. New technologies and fresh uses for established procedures make imaging effective in both assessing and treating prostate cancer. PMID:19457806

  15. Clinical variability and molecular heterogeneity in prostate cancer

    PubMed Central

    Shoag, Jonathan; Barbieri, Christopher E

    2016-01-01

    Prostate cancer is a clinically heterogeneous disease, with some men having indolent disease that can safely be observed, while others have aggressive, lethal disease. Over the past decade, researchers have begun to unravel some of the genomic heterogeneity that contributes to these varying clinical phenotypes. Distinct molecular sub-classes of prostate cancer have been identified, and the uniqueness of these sub-classes has been leveraged to predict clinical outcomes, design novel biomarkers for prostate cancer diagnosis, and develop novel therapeutics. Recent work has also elucidated the temporal and spatial heterogeneity of prostate cancer, helping us understand disease pathogenesis, response to therapy, and progression. New genomic techniques have provided us with a window into the remarkable clinical and genomic heterogeneity of prostate cancer, and this new perspective will increasingly impact patient care. PMID:27080479

  16. Histotripsy Fractionation of Prostate Tissue: Local Effects and Systemic Response in a Canine Model

    PubMed Central

    Hempel, Christopher R.; Hall, Timothy L; Cain, Charles A.; Fowlkes, J. Brian; Xu, Zhen; Roberts, William W.

    2010-01-01

    Purpose Histotripsy is an extracorporeal ultrasound (US) technology that utilizes cavitational mechanisms to produce non-thermal tissue destruction. Previously, we demonstrated the feasibility of histotripsy for fractionation and immediate debulking of prostate tissue. The purpose of this study is to characterize the local effects and systemic response after histotripsy treatment of prostate tissue in an in-vivo canine model. Materials and Methods Histotripsy was applied transabdominally to the prostate in eighteen intact male canine subjects under general anesthesia. Acoustic bursts (4 microseconds) were delivered at 300 Hz pulse repetition rate from a highly focused 750 kHz piezoelectric US transducer (15 cm aperture, 3×3×8 mm focal volume). The prostate and surrounding structures were harvested at prescribed time points (0, 7, 28, or 56 days) following histotripsy. Blood and urine parameters were assessed periodically while clinical evaluation incorporating a validated veterinary pain scale was performed daily. Results Conventional transrectal US imaging facilitated targeting of the focal volume and provided real-time assessment of cavitation activity. Fractionation of the targeted volume and clearance of the resultant debris with urination produced a treatment cavity within each prostate. No acoustic collateral damage was seen and urothelialization of the treatment cavity occurred within 28 days of treatment. Only transient lab abnormalities and minimal hematuria were noted after treatment. Pain scores revealed only mild post treatment discomfort. Conclusions Histotripsy produced consistent tissue fractionation and prostate debulking without collateral acoustic injury or clinical side effects and was well tolerated in the canine model. PMID:21334667

  17. The feasibility of endorectal MR elastography for prostate cancer localization.

    PubMed

    Arani, Arvin; Plewes, Donald; Krieger, Axel; Chopra, Rajiv

    2011-12-01

    The objectives of this study were to evaluate the feasibility of using a rigid radio-frequency receiver endorectal coil for intracavitary prostate magnetic resonance elastography (MRE) and to demonstrate the capability of this technique for generating stiffness maps over a typical prostate volume. An endorectal coil is currently used to help improve the signal-to-noise ratio of images acquired with multiparametric magnetic resonance imaging. We propose that this same coil could also serve to generate shear waves in the prostate gland during imaging, opening up the possibility of incorporating prostate stiffness characterization into multiparametric magnetic resonance imaging. Prostate cancer has been shown to change the elasticity of tissue, suggesting that stiffness imaging (elastography) may provide supplementary diagnostic information. A rigid endorectal coil was mechanically coupled to a piezoceramic actuator and used to investigate full volume (27 slices, 2-mm thick) endorectal MRE in a prostate mimicking phantom. The low-amplitude vibrations (± 8-38 μm displacements) necessary to perform endorectal MRE did not affect the signal-to noise ratio of the coil and endorectal MRE was capable of resolving 0.1 cc (0.6 cm diameter) spherical inclusion volumes. Therefore, the results of this study, in combination with current clinical practice, motivate clinical evaluation of endorectal MRE in patients. PMID:21574182

  18. Management of Biochemical Recurrence after Primary Localized Therapy for Prostate Cancer

    PubMed Central

    Darwish, Oussama M.; Raj, Ganesh V.

    2012-01-01

    Clinically localized prostate cancer is typically managed by well established therapies like radical prostatectomy, brachytherapy, and external beam radiation therapy. While many patients can be cured with definitive local therapy, some will have biochemical recurrence (BCR) of disease detected by a rising serum prostate-specific antigen (PSA). Management of these patients is nuanced and controversial. The natural history indicates that a majority of patients with BCR will not die from prostate cancer but from other causes. Despite this, a vast majority of patients with BCR are empirically treated with non-curable systemic androgen deprivation therapy (ADT), with its myriad of real and potential side effects. In this review article, we examined the very definition of BCR after definitive local therapy, the current status of imaging studies in its evaluation, the need for additional therapies, and the factors involved in the decision making in the choice of additional therapies. This review aims to help clinicians with the management of patients with BCR. The assessment of prognostic factors including absolute PSA level, time to recurrence, PSA kinetics, multivariable nomograms, imaging, and biopsy of the prostatic bed may help stratify the patients into localized or systemic recurrence. Patients with low-risk of systemic disease may be cured by a salvage local therapy, while those with higher risk of systemic disease may be offered the option of ADT or a clinical trial. An algorithm incorporating these factors is presented. PMID:22655274

  19. Clinical Evaluation of Benign Prostatic Hyperplasia

    PubMed Central

    McVary, Kevin T

    2003-01-01

    Benign prostatic hyperplasia (BPH) is the most common neoplastic condition afflicting men and constitutes a major factor impacting male health. Clinical evaluation to assess the presence and degree of voiding dysfunction and/or the role of BPH in its presence has an increasingly broad spectrum of treatment goals. The goals of the evaluation of such men are to identify the patient’s voiding or, more appropriately, urinary tract problems, both symptomatic and physiologic; to establish the etiologic role of BPH in these problems; to evaluate the necessity for and probability of success and risks of various therapeutic approaches; and to present the results of these assessments to the patient so he can make an informed decision about management recommendations and available alternatives. PMID:16985961

  20. Clinical Evaluation of Benign Prostatic Hyperplasia

    PubMed Central

    McVary, Kevin T

    2003-01-01

    Benign prostatic hyperplasia (BPH) is the most common neoplastic condition afflicting men and constitutes a major factor impacting male health. Clinical evaluation to assess the presence and degree of voiding dysfunction and/or the role of BPH in its presence has an increasingly broad spectrum of treatment goals. The goals of the evaluation of such men are to identify the patient’s voiding or, more appropriately, urinary tract problems, both symptomatic and physiologic; to establish the etiologic role of BPH in these problems; to evaluate the necessity for and probability of success and risks of various therapeutic approaches; and to present the results of these assessments to the patient so he can make an informed decision about management recommendations and available alternatives. PMID:16985968

  1. Prostate Cancer in Young Men: An Important Clinical Entity

    PubMed Central

    Salinas, Claudia A.; Tsodikov, Alex; Ishak-Howard, Miriam; Cooney, Kathleen A.

    2014-01-01

    Prostate cancer is considered a disease of older men, but today over 10% of new diagnoses occur in U.S. men ≤ 55 years. Early onset prostate cancer, i.e., diagnosed at ≤55 years, differs from prostate cancer in older men in several ways. Among men diagnosed with high grade and stage prostate cancer, men with early onset prostate cancer are more likely to die of their cancer, with higher cause-specific mortality than all others except those diagnosed over age 80. This suggests that important biological differences may exist in early onset disease compared to late onset disease. Furthermore, early onset prostate cancer has been shown to have a more significant genetic component indicating that this group may benefit more than most from evaluation of genetic risk. Clinically, although the majority of cases ≤ 55 years are diagnosed with low risk disease, their extended life expectancy exposes them to long-term risk of disease progression resulting in death from prostate cancer, but also to prolonged impact from treatment-related morbidities. These patients pose unique challenges and opportunities for both the research and clinical communities. We therefore suggest that early onset prostate cancer is a distinct phenotype, from both an etiologic and clinical perspective, that deserves further attention. PMID:24818853

  2. Ejaculatory Function After Permanent {sup 125}I Prostate Brachytherapy for Localized Prostate Cancer

    SciTech Connect

    Huyghe, Eric Delannes, Martine; Wagner, Fabien M.; Delaunay, Boris; Nohra, Joe; Thoulouzan, Matthieu; Shut-Yee, J. Yeung; Plante, Pierre; Soulie, Michel; Thonneau, Patrick; Bachaud, Jean Marc

    2009-05-01

    Purpose: Ejaculatory function is an underreported aspect of male sexuality in men treated for prostate cancer. We conducted the first detailed analysis of ejaculatory function in patients treated with permanent {sup 125}I prostate brachytherapy for localized prostate cancer. Patients and Methods: Of 270 sexually active men with localized prostate cancer treated with permanent {sup 125}I prostate brachytherapy, 241 (89%), with a mean age of 65 years (range, 43-80), responded to a mailed questionnaire derived from the Male Sexual Health Questionnaire regarding ejaculatory function. Five aspects of ejaculatory function were examined: frequency, volume, dry ejaculation, pleasure, and pain. Results: Of the 241 sexually active men, 81.3% had conserved ejaculatory function after prostate brachytherapy; however, the number of patients with rare/absent ejaculatory function was double the pretreatment number (p < .0001). The latter finding was correlated with age (p < .001) and the preimplant International Index of Erectile Function score (p < .001). However, 84.9% of patients with maintained ejaculatory function after implantation reported a reduced volume of ejaculate compared with 26.9% before (p < .001), with dry ejaculation accounting for 18.7% of these cases. After treatment, 30.3% of the patients experienced painful ejaculation compared with 12.9% before (p = .0001), and this was associated with a greater number of implanted needles (p = .021) and the existence of painful ejaculation before implantation (p < .0001). After implantation, 10% of patients who continued to be sexually active experienced no orgasm compared with only 1% before treatment. in addition, more patients experienced late/difficult or weak orgasms (p = .001). Conclusion: Most men treated with brachytherapy have conserved ejaculatory function after prostate brachytherapy. However, most of these men experience a reduction in volume and a deterioration in orgasm.

  3. Focal Therapy in the Management of Prostate Cancer: An Emerging Approach for Localized Prostate Cancer

    PubMed Central

    Nomura, Takeo; Mimata, Hiromitsu

    2012-01-01

    A widespread screening with prostate-specific antigen (PSA) has led increased diagnosis of localized prostate cancer along with a reduction in the proportion of advanced-stage disease at diagnosis. Over the past decade, interest in focal therapy as a less morbid option for the treatment of localized low-risk prostate cancer has recently been renewed due to downward stage migration. Focal therapy stands midway between active surveillance and radical treatments, combining minimal morbidity with cancer control. Several techniques of focal therapy have potential for isolated ablation of a tumor focus with sparing of uninvolved surround tissue demonstrating excellent short-term cancer control and a favorable patient's quality of life. However, to date, tissue ablation has mostly used for near-whole prostate gland ablation without taking advantage of accompanying the technological capabilities. The available ablative technologies include cryotherapy, high-intensity focused ultrasound (HIFU), and vascular-targeted photodynamic therapy (VTP). Despite the interest in focal therapy, this technology has not yet been a well-established procedure nor provided sufficient data, because of the lack of randomized trial comparing the efficacy and morbidity of the standard treatment options. In this paper we briefly summarize the recent data regarding focal therapy for prostate cancer and these new therapeutic modalities. PMID:22593764

  4. Development of ProCaRS Clinical Nomograms for Biochemical Failure-free Survival Following Either Low-Dose Rate Brachytherapy or Conventionally Fractionated External Beam Radiation Therapy for Localized Prostate Cancer

    PubMed Central

    Warner, Andrew; Pickles, Tom; Crook, Juanita; Martin, Andre-Guy; Souhami, Luis; Catton, Charles; Lukka, Himu

    2015-01-01

    Purpose: Although several clinical nomograms predictive of biochemical failure-free survival (BFFS) for localized prostate cancer exist in the medical literature, making valid comparisons can be challenging due to variable definitions of biochemical failure, the disparate distribution of prognostic factors, and received treatments in patient populations. The aim of this investigation was to develop and validate clinically-based nomograms for 5-year BFFS using the ASTRO II “Phoenix” definition for two patient cohorts receiving low-dose rate (LDR) brachytherapy or conventionally fractionated external beam radiation therapy (EBRT) from a large Canadian multi-institutional database. Methods and Materials: Patients were selected from the GUROC (Genitourinary Radiation Oncologists of Canada) Prostate Cancer Risk Stratification (ProCaRS) database if they received (1) LDR brachytherapy ≥ 144 Gy (n=4208) or (2) EBRT ≥ 70 Gy  (n=822). Multivariable Cox regression analysis for BFFS was performed separately for each cohort and used to generate clinical nomograms predictive of 5-year BFFS. Nomograms were validated using calibration plots of nomogram predicted probability versus observed probability via Kaplan-Meier estimates. Results: Patients receiving LDR brachytherapy had a mean age of 64 ± 7 years, a mean baseline PSA of 6.3 ± 3.0 ng/mL, 75% had a Gleason 6, and 15% had a Gleason 7, whereas patients receiving EBRT had a mean age of 70 ± 6 years, a mean baseline PSA of 11.6 ± 10.7 ng/mL, 30% had a Gleason 6, 55% had a Gleason 7, and 14% had a Gleason 8-10. Nomograms for 5-year BFFS included age, use and duration of androgen deprivation therapy (ADT), baseline PSA, T stage, and Gleason score for LDR brachytherapy and an ADT (months), baseline PSA, Gleason score, and biological effective dose (Gy) for EBRT. Conclusions: Clinical nomograms examining 5-year BFFS were developed for patients receiving either LDR brachytherapy or conventionally fractionated EBRT and

  5. Iodine 125 interstitial irradiation for localized prostate cancer.

    PubMed Central

    Kumar, P. P.; Good, R. R.; Bartone, F. F.

    1990-01-01

    We present the technique, complications, and 5-year results of transperineal percutaneous template permanent interstitial iodine 125 endocurietherapy of localized prostate cancer in 85 treated patients. The 5-year outcome appears similar to that of external beam radiation therapy or radical surgery, but the iatrogenic mortality, morbidity, treatment time, and hospitalization are significantly reduced. Images Figure 1 Figure 2 Figure 3 PMID:2319613

  6. Targeting Neuroendocrine Prostate Cancer: Molecular and Clinical Perspectives

    PubMed Central

    Vlachostergios, Panagiotis J.; Papandreou, Christos N.

    2015-01-01

    Neuroendocrine prostate carcinoma, either co-present with the local adenocarcinoma disease or as a result of transdifferentiation later in time, was described as one major process of emerging resistance to androgen deprivation therapies, and at the clinical level it is consistent with the development of rapidly progressive visceral disease, often in the absence of elevated serum prostate-specific antigen level. Until present, platinum-based chemotherapy has been the only treatment modality, able to produce a fair amount of responses but of short duration. Recently, several efforts for molecular characterization of this lethal phenotype have resulted in identification of novel signaling factors involved in microenvironment interactions, mitosis, and neural reprograming as potential therapeutic targets. Ongoing clinical testing of specific inhibitors of these targets, for example, Aurora kinase A inhibitors, in carefully selected patients and exploitation of expression changes of the target before and after manipulation is anticipated to increase the existing data and facilitate therapeutic decision making at this late stage of the disease when hormonal manipulations, even with the newest androgen-directed therapies are no longer feasible. PMID:25699233

  7. Racial Differences in Diffusion of Intensity-Modulated Radiation Therapy for Localized Prostate Cancer.

    PubMed

    Cobran, Ewan K; Chen, Ronald C; Overman, Robert; Meyer, Anne-Marie; Kuo, Tzy-Mey; O'Brien, Jonathon; Sturmer, Til; Sheets, Nathan C; Goldin, Gregg H; Penn, Dolly C; Godley, Paul A; Carpenter, William R

    2016-09-01

    Intensity-modulated radiation therapy (IMRT), an innovative treatment option for prostate cancer, has rapidly diffused over the past decade. To inform our understanding of racial disparities in prostate cancer treatment and outcomes, this study compared diffusion of IMRT in African American (AA) and Caucasian American (CA) prostate cancer patients during the early years of IMRT diffusion using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. A retrospective cohort of 947 AA and 10,028 CA patients diagnosed with localized prostate cancer from 2002 through 2006, who were treated with either IMRT or non-IMRT as primary treatment within 1 year of diagnoses was constructed. Logistic regression was used to examine potential differences in diffusion of IMRT in AA and CA patients, while adjusting for socioeconomic and clinical covariates. A significantly smaller proportion of AA compared with CA patients received IMRT for localized prostate cancer (45% vs. 53%, p < .0001). Racial differences were apparent in multivariable analysis though did not achieve statistical significance, as time and factors associated with race (socioeconomic, geographic, and tumor related factors) explained the preponderance of variance in use of IMRT. Further research examining improved access to innovative cancer treatment and technologies is essential to reducing racial disparities in cancer care.

  8. The Influence of Prostate Volume on Outcome After High-Dose-Rate Brachytherapy Alone for Localized Prostate Cancer

    SciTech Connect

    Le, Hien Rojas, Ana; Alonzi, Roberto; Hughes, Robert; Ostler, Peter; Lowe, Gerry; Bryant, Linda; Hoskin, Peter

    2013-10-01

    Objective: To determine whether late genitourinary toxicity, biochemical control of prostate cancer, and dosimetric parameters in patients with large prostate glands is different from those variables in men with smaller glands after treatment with high-dose-rate brachytherapy alone (HDR-BT). Methods: From November 2003 to July 2009, 164 patients with locally advanced prostate carcinoma were sequentially enrolled and treated with 34 or 36 Gy in 4 fractions and 31.5 Gy in 3 fractions of {sup 192}Ir HDR-BT alone. The median follow-up time was 71 months. Gland size was not considered in the selection criteria for this study. Estimates of freedom from biochemical relapse (FFbR) and late morbidity, stratified by median clinical target volume (CTV), were obtained, and differences were compared. Results: The median CTV volume was 60 cc (range, 15-208 cc). Dose–volume parameters D90 and V100 (ie, minimum dose to 90% of the prostate volume and volume receiving 100% of the prescribed isodose) achieved in patients with glands ≥60 cc were not significantly different from those with glands <60 cc (P≥.2). Nonetheless, biochemical control in patients with larger CTV was significantly higher (91% vs 78% at 6 years; P=.004). In univariate and multivariate analysis, CTV was a significant predictor for risk of biochemical relapse. This was not at the expense of an increase in either moderate (P=.6) or severe (P=.3) late genitourinary toxicity. The use of hormonal therapy was 17% lower in the large gland group (P=.01). Conclusions: Prostate gland size does not affect dosimetric parameters in HDR-BT assessed by D90 and V100. In patients with larger glands, a significantly higher biochemical control of disease was observed, with no difference in late toxicity. This improvement cannot be attributed to differences in dosimetry. Gland size should not be considered in the selection of patients for HDR-BT.

  9. Intrafractional prostate motion during external beam radiotherapy monitored by a real-time target localization system.

    PubMed

    Tong, Xu; Chen, Xiaoming; Li, Jinsheng; Xu, Qianqian; Lin, Mu-Han; Chen, Lili; Price, Robert A; Ma, Chang-Ming

    2015-03-08

    This paper investigates the clinical significance of real-time monitoring of intrafractional prostate motion during external beam radiotherapy using a commercial 4D localization system. Intrafractional prostate motion was tracked during 8,660 treatment fractions for 236 patients. The following statistics were analyzed: 1) the percentage of fractions in which the prostate shifted 2-7 mm for a certain duration; 2) the proportion of the entire tracking time during which the prostate shifted 2-7mm; and 3) the proportion of each minute in which the shift exceeded 2-7 mm. The ten patients exhibiting maximum intrafractional-motion patterns were analyzed separately. Our results showed that the percentage of fractions in which the prostate shifted by > 2, 3, 5, and 7 mm off the baseline in any direction for > 30 s was 56.8%, 27.2%, 4.6%, and 0.7% for intact prostate and 68.7%, 35.6%, 10.1%, and 1.8% for postprostatectomy patients, respectively. For the ten patients, these percentages were 91.3%, 72.4%, 36.3%, and 6%, respectively. The percentage of tracking time during which the prostate shifted > 2, 3, 5, and 7 mm was 27.8%, 10.7%, 1.6%, and 0.3%, respectively, and it was 56.2%, 33.7%, 11.2%, and 2.1%, respectively, for the ten patients. The percentage of tracking time for a > 3 mm posterior motion was four to five times higher than that in other directions. For treatments completed in 5 min (VMAT) and 10 min (IMRT), the proportion for the prostate to shift by > 3mm was 4% and 12%, respectively. Although intrafractional prostate motion was generally small, caution should be taken for patients who exhibit frequent large intrafractional motion. For those patients, adjustment of patient positioning may be necessary or a larger treatment margin may be used. After the initial alignment, the likelihood of prostate motion increases with time. Therefore, it is favorable to use advanced techniques (e.g., VMAT) that require less delivery time in order to reduce the treatment

  10. Clinical utility of radiolabeled monoclonal antibodies in prostate cancer.

    PubMed

    David, Kevin A; Milowsky, Matthew I; Kostakoglu, Lale; Vallabhajosula, Shankar; Goldsmith, Stanley J; Nanus, David M; Bander, Neil H

    2006-03-01

    Prostate cancer represents an ideal target for radioimmunotherapy based on the pattern of spread, including bone marrow and lymph nodes, sites that typically receive high levels of circulating antibody, and the small volume of disease, ideally suited for antibody delivery and antigen access. This review explores possible antibody targets in prostate cancer and focuses on the potential role for radioimmunotherapy by highlighting several clinical trials involving radiolabeled anti-prostate-specific membrane antigen monoclonal antibody J591. Prostate-specific membrane antigen, a highly prostate-restricted transmembrane glycoprotein with increased expression in high-grade, metastatic, and hormone-refractory disease, represents an ideal target for monoclonal antibody therapy in prostate cancer. Radiolabeled anti-prostate-specific membrane antigen monoclonal antibody J591 trials using the radiometals yttrium-90 and lutetium-177 have demonstrated manageable myelotoxicity, no significant nonhematologic toxicity, excellent targeting of soft-tissue and bone metastases, and preliminary efficacy including prostate-specific antigen and measurable disease responses. Additional studies are under way to better define the activity of radiolabeled antibody therapy as well as the role for fractionated therapy and combination approaches with taxane-based chemotherapy.

  11. Race and Survival Following Brachytherapy-Based Treatment for Men With Localized or Locally Advanced Adenocarcinoma of the Prostate

    SciTech Connect

    Winkfield, Karen M.; Chen Minghui; Dosoretz, Daniel E.; Salenius, Sharon A.; Katin, Michael; Ross, Rudi; D'Amico, Anthony V.

    2011-11-15

    Purpose: We investigated whether race was associated with risk of death following brachytherapy-based treatment for localized prostate cancer, adjusting for age, cardiovascular comorbidity, treatment, and established prostate cancer prognostic factors. Methods: The study cohort was composed of 5,360 men with clinical stage T1-3N0M0 prostate cancer who underwent brachytherapy-based treatment at 20 centers within the 21st Century Oncology consortium. Cox regression multivariable analysis was used to evaluate the risk of death in African-American and Hispanic men compared to that in Caucasian men, adjusting for age, pretreatment prostate-specific antigen (PSA) level, Gleason score, clinical T stage, year and type of treatment, median income, and cardiovascular comorbidities. Results: After a median follow-up of 3 years, there were 673 deaths. African-American and Hispanic races were significantly associated with an increased risk of all-cause mortality (ACM) (adjusted hazard ratio, 1.77 and 1.79; 95% confidence intervals, 1.3-2.5 and 1.2-2.7; p < 0.001 and p = 0.005, respectively). Other factors significantly associated with an increased risk of death included age (p < 0.001), Gleason score of 8 to 10 (p = 0.04), year of brachytherapy (p < 0.001), and history of myocardial infarction treated with stent or coronary artery bypass graft (p < 0.001). Conclusions: After adjustment for prostate cancer prognostic factors, age, income level, and revascularized cardiovascular comorbidities, African-American and Hispanic races were associated with higher ACM in men with prostate cancer. Additional causative factors need to be identified.

  12. Multiparametric MRI and targeted prostate biopsy: Improvements in cancer detection, localization, and risk assessment

    PubMed Central

    Bjurlin, Marc A.; Mendhiratta, Neil; Wysock, James S.

    2016-01-01

    Introduction Multiparametric-MRI (mp-MRI) is an evolving noninvasive imaging modality that increases the accurate localization of prostate cancer at the time of MRI targeted biopsy, thereby enhancing clinical risk assessment, and improving the ability to appropriately counsel patients regarding therapy. Material and methods We used MEDLINE/PubMed to conduct a comprehensive search of the English medical literature. Articles were reviewed, data was extracted, analyzed, and summarized. In this review, we discuss the mp-MRI prostate exam, its role in targeted prostate biopsy, along with clinical applications and outcomes of MRI targeted biopsies. Results Mp-MRI, consisting of T2-weighted imaging, diffusion-weighted imaging, dynamic contrast-enhanced imaging, and possibly MR spectroscopy, has demonstrated improved specificity in prostate cancer detection as compared to conventional T2-weighted images alone. An MRI suspicion score has been developed and is depicted using an institutional Likert or, more recently, a standardized reporting scale (PI-RADS). Techniques of MRI-targeted biopsy include in-gantry MRI guided biopsy, TRUS-guided visual estimation biopsy, and software co-registered MRI-US guided biopsy (MRI-US fusion). Among men with no previous biopsy, MRI-US fusion biopsy demonstrates up to a 20% increase in detection of clinically significant cancers compared to systematic biopsy while avoiding a significant portion of low risk disease. These data suggest a potential role in reducing over-detection and, ultimately, over-treatment. Among men with previous negative biopsy, 72–87% of cancers detected by MRI targeted biopsy are clinically significant. Among men with known low risk cancer, repeat biopsy by MR-targeting improves risk stratification in selecting men appropriate for active surveillance secondarily reducing the need for repetitive biopsy during surveillance. Conclusions Use of mp-MRI for targeting prostate biopsies has the potential to reduce the

  13. Markers of Field Cancerization: Proposed Clinical Applications in Prostate Biopsies

    PubMed Central

    Trujillo, Kristina A.; Jones, Anna C.; Griffith, Jeffrey K.; Bisoffi, Marco

    2012-01-01

    Field cancerization denotes the occurrence of genetic, epigenetic, and biochemical aberrations in structurally intact cells in histologically normal tissues adjacent to cancerous lesions. This paper tabulates markers of prostate field cancerization known to date and discusses their potential clinical value in the analysis of prostate biopsies, including diagnosis, monitoring progression during active surveillance, and assessing efficacy of presurgical neoadjuvant and focal therapeutic interventions. PMID:22666601

  14. Clinical Collection and Protein Properties of Expressed Prostatic Secretions as a Source for Biomarkers of Prostatic Disease

    PubMed Central

    Drake, Richard R.; White, Krista Y.; Fuller, Thomas W.; Igwe, Elena; Clements, Mary Ann; Nyalwidhe, Julius O.; Given, Robert W.; Lance, Raymond S.; Semmes, O. John

    2009-01-01

    The prostate gland secretes many proteins in a prostatic fluid that combines with seminal vesicle derived fluids to promote sperm activation and function. Proximal fluids of the prostate that can be collected clinically are seminal plasma and expressed-prostatic secretion (EPS) fluids. EPS represents the fluid being secreted by the prostate following a digital rectal prostate massage, which in turn can be collected in voided urine post-exam. This collection is not disruptive to a standard urological exam, and it can be repeatedly collected from men across all prostatic disease states. A direct EPS fluid can also be collected under anesthesia prior to prostatectomy. While multiple genetic assays for prostate cancer detection are being developed for the shed epithelial cell fraction of EPS urines, the remaining fluid that contains many prostate-derived proteins has been minimally characterized. Approaches to optimization and standardization of EPS collection consistent with current urological exam and surgical practices are described, and initial proteomic and glycomic evaluations of the of EPS fluid are summarized for prostate specific antigen and prostatic acid phosphatase. Continued characterization of the prostate specific protein components of EPS urine combined with optimization of clinical collection procedures should facilitate discovery of new biomarkers for prostate cancer. PMID:19457353

  15. Neuroendocrine prostate cancer: subtypes, biology, and clinical outcomes.

    PubMed

    Aggarwal, Rahul; Zhang, Tian; Small, Eric J; Armstrong, Andrew J

    2014-05-01

    Neuroendocrine prostate cancer (NEPC) encompasses various clinical contexts, ranging from the de novo presentation of small cell prostatic carcinoma to a treatment-emergent transformed phenotype that arises from typical adenocarcinoma of the prostate. The development of resistance to potent androgen receptor signaling inhibition may be associated with the emergence of aggressive phenotype, advanced castration-resistant NEPC. Clinically, small cell prostate cancer and NEPC are often manifested by the presence of visceral or large soft tissue metastatic disease, a disproportionately low serum prostate-specific antigen level relative to the overall burden of disease, and a limited response to targeting of the androgen signaling axis. These tumors are often characterized by loss of androgen receptor expression, loss of retinoblastoma tumor suppressor copy number or expression, amplification of Aurora kinase A and N-Myc, and activation of the PI3K pathway. However, a consensus phenotype-genotype definition of NEPC has yet to emerge, and molecularly based biomarkers are needed to expand on traditional morphologic and immunohistochemical markers of NEPC to fully define the spectrum of this aggressive, androgen receptor-independent disease. Emerging studies implicate a shared clonal origin with prostatic adenocarcinoma in many cases, with the adaptive emergence of unique cellular programming and gene expression profiles. Ongoing clinical studies are focused on developing novel targeted therapeutic approaches for this high-risk, lethal subset of disease, to improve on the limited durations of response often observed with traditional platinum-based chemotherapy.

  16. Efficient use of continuous, real-time prostate localization

    NASA Astrophysics Data System (ADS)

    Malinowski, Kathleen T.; Noel, Camille; Roy, Meghana; Willoughby, Twyla; Djemi, Toufik; Jani, Shirish; Solberg, Timothy; Liu, David; Levine, Lisa; Parikh, Parag J.

    2008-09-01

    Recent technological advances make it possible to monitor prostate movement during radiation delivery. Using previously published data from 35 patients who underwent continuous localization during prostate cancer treatment, we simulated various interventions to identify the radiation-gating and patient-repositioning strategies that least prolonged the time to complete the daily treatment. Acceptable response protocols were those that resulted in at least 95% of patients' prostates remaining within the planning margins at least 95% of the time. Gating and repositioning were not necessary for margins of 7 or 10 mm because of the rarity of excursions at these margins. However, intervention was routinely necessary for margins of 3 and 5 mm. In simulated interventions for which the therapist could reposition the treatment couch without entering the room, the most time-efficient response protocol was to reposition the couch immediately after the prostate position was outside the treatment margins. In simulations in which the therapist had to enter the room to reposition the couch, overall treatment time could be reduced and accuracy could be increased by manually gating treatment for 11 and 21 s for 3- and 5-mm margins, respectively, before interrupting treatment to reposition the treatment couch.

  17. Comparison of clinical symptoms scored according to the National Institutes of Health chronic prostatitis symptoms index and assessment of antimicrobial treatment in patients with chronic prostatitis syndrome.

    PubMed

    Skerk, Visnja; Roglić, S; Cajić, V; Markotić, A; Radonić, A; Skerk, Vedrana; Granić, J; Zidovec-Lepej, S; Parazajder, J; Begovac, J

    2009-04-01

    We examined a total of 194 patients over 18 years of age with chronic prostatitis syndrome and no evidence of structural or functional lower genitourinary tract abnormalities. The following data were obtained for each patient: clinical history--the severity of chronic prostatitis symptoms scored by a Croatian translation of the NiH CPSI questionnaire, clinical status including digitorectal examination, urethral swab specimens, and selective samples of urine and expressed prostatic secretion, according to the 4-glass localization test (meares and Stamey localization technique). Patients were treated orally with antimicrobial agents in doses and duration according to clinical practice in Croatia. An infectious etiology was determined in 169 (87%) patients. Chlamydia trachomatis was the causative pathogen in 38 (20%), Trichomonas vaginalis in 35 (18%), Enterococcus in 36 (19%) and Escherichia coli in 35 (18%) patients. In the remaining 25 patients the following causative pathogens were found: Ureaplasma urealyticum, Proteus mirabilis, Klebsiella pneumoniae, Streptococcus agalactiae and Pseudomonas aeruginosa. Comparison of symptoms scores and effect on quality of life has shown that the most severe clinical presentation of disease was recorded in patients with chronic bacterial prostatitis caused by E. coli and Enterococcus (p<0.001). Clinical success was paralleled by bacteriological eradication in chronic bacterial prostatitis caused by C. trachomatis, Enterococcus and E. coli (kappa >0.2<0.5), but not in inflammatory chronic pelvic pain syndrome caused by T. vaginalis. PMID:19423471

  18. Daily variations in delivered doses in patients treated with radiotherapy for localized prostate cancer

    SciTech Connect

    Kupelian, Patrick A. . E-mail: patrick.kupelian@orhs.org; Langen, Katja M.; Zeidan, Omar A.; Meeks, Sanford L.; Willoughby, Twyla R.; Wagner, Thomas H.; Jeswani, Sam; Ruchala, Kenneth J.; Haimerl, Jason; Olivera, Gustavo H.

    2006-11-01

    Purpose: The aim of this work was to study the variations in delivered doses to the prostate, rectum, and bladder during a full course of image-guided external beam radiotherapy. Methods and Materials: Ten patients with localized prostate cancer were treated with helical tomotherapy to 78 Gy at 2 Gy per fraction in 39 fractions. Daily target localization was performed using intraprostatic fiducials and daily megavoltage pelvic computed tomography (CT) scans, resulting in a total of 390 CT scans. The prostate, rectum, and bladder were manually contoured on each CT by a single physician. Daily dosimetric analysis was performed with dose recalculation. The study endpoints were D95 (dose to 95% of the prostate), rV2 (absolute rectal volume receiving 2 Gy), and bV2 (absolute bladder volume receiving 2 Gy). Results: For the entire cohort, the average D95 ({+-}SD) was 2.02 {+-} 0.04 Gy (range, 1.79-2.20 Gy). The average rV2 ({+-}SD) was 7.0 {+-} 8.1 cc (range, 0.1-67.3 cc). The average bV2 ({+-}SD) was 8.7 {+-} 6.8 cc (range, 0.3-36.8 cc). Unlike doses for the prostate, there was significant daily variation in rectal and bladder doses, mostly because of variations in volume and shape of these organs. Conclusion: Large variations in delivered doses to the rectum and bladder can be documented with daily megavoltage CT scans. Image guidance for the targeting of the prostate, even with intraprostatic fiducials, does not take into account the variation in actual rectal and bladder doses. The clinical impact of techniques that take into account such dosimetric parameters in daily patient set-ups should be investigated.

  19. Hypofractionated intensity-modulated radiotherapy in patients with localized prostate cancer: a preliminary study

    PubMed Central

    Kang, Hye Jin; Son, Seok Hyun; Kim, Myungsoo; Jo, In Young; Lee, So Jung; Lee, Dong Hwan; Suh, Hong Jin; Choi, Yong Sun

    2016-01-01

    Purpose The aim of this work was to assess the efficacy and tolerability of hypofractionated intensity-modulated radiotherapy (IMRT) in patients with localized prostate cancer. Materials and Methods Thirty-nine patients who received radical hypofractionated IMRT were retrospectively reviewed. Based on a pelvic lymph node involvement risk of 15% as the cutoff value, we decided whether to deliver treatment prostate and seminal vesicle only radiotherapy (PORT) or whole pelvis radiotherapy (WPRT). Sixteen patients (41%) received PORT with prostate receiving 45 Gy in 4.5 Gy per fraction in 2 weeks and the other 23 patients (59%) received WPRT with the prostate receiving 72 Gy in 2.4 Gy per fraction in 6 weeks. The median equivalent dose in 2 Gy fractions to the prostate was 79.9 Gy based on the assumption that the α/β ratio is 1.5 Gy. Results The median follow-up time was 38 months (range, 4 to 101 months). The 3-year biochemical failure-free survival rate was 88.2%. The 3-year clinical failure-free and overall survival rates were 94.5% and 96.3%, respectively. The rates of grade 2 acute genitourinary (GU) and gastrointestinal (GI) toxicities were 20.5% and 12.8%, respectively. None of the patients experienced grade ≥3 acute GU and GI toxicities. The grade 2-3 late GU and GI toxicities were found in 8.1% and 5.4% of patients, respectively. No fatal late toxicity was observed. Conclusion Favorable biochemical control with low rates of toxicity was observed after hypofractionated IMRT, suggesting that our radiotherapy schedule can be an effective treatment option in the treatment of localized prostate cancer. PMID:27104166

  20. Psychological aspects of prostate cancer: a clinical review.

    PubMed

    De Sousa, A; Sonavane, S; Mehta, J

    2012-06-01

    Prostate cancer is the most common non-skin cancer in men. It is fraught with both physical and psychological symptomatology. Depression, anxiety, stress, fatigue, pain and psychosocial factors all affect the patient with prostate cancer. Impotence, erectile dysfunction, sexual issues and incontinence in these patients complicate matters further. Anxiety may exist both before testing and while awaiting test results. Confusion over choosing from various interventions often adds to anxiety and depression in these patients. Various demographic factors and the developmental stage of the couple affect these psychological symptoms. The caregiver may undergo significant psychological turmoil while caring for a patient diagnosed with prostate cancer, which is addressed. The role of nurses in the management of prostate cancer is discussed. The present review looks at psychological issues in patients with prostate cancer from a clinical perspective, with the aim of highlighting these issues for the clinical urologist dealing with these patients. It also explores the consultation-liaison relationship between psychiatrists, psychologists and urologists as a team for the multimodal management of prostate cancer. PMID:22212706

  1. Local prostate cancer radiotherapy after prostate-specific antigen progression during primary hormonal therapy

    PubMed Central

    2012-01-01

    Background The outcome of patients after radiotherapy (RT) for localized prostate cancer in case of prostate-specific antigen (PSA) progression during primary hormonal therapy (HT) is not well known. Methods A group of 27 patients presenting with PSA progression during primary HT for local prostate cancer RT was identified among patients who were treated in the years 2000–2004 either using external-beam RT (EBRT; 70.2Gy; n=261) or Ir-192 brachytherapy as a boost to EBRT (HDR-BT; 18Gy + 50.4Gy; n=71). The median follow-up period after RT was 68 months. Results Median biochemical recurrence free (BRFS), disease specific (DSS) and overall survival (OS) for patients with PSA progression during primary HT was found to be only 21, 54 and 53 months, respectively, with a 6-year BRFS, DSS and OS of 19%, 41% and 26%. There were no significant differences between different RT concepts (6-year OS of 27% after EBRT and 20% after EBRT with HDR-BT). Considering all 332 patients in multivariate Cox regression analysis, PSA progression during initial HT, Gleason score>6 and patient age were found to be predictive for lower OS (p<0.001). The highest hazard ratio resulted for PSA progression during initial HT (7.2 in comparison to patients without PSA progression during primary HT). PSA progression and a nadir >0.5 ng/ml during initial HT were both significant risk factors for biochemical recurrence. Conclusions An unfavourable prognosis after PSA progression during initial HT needs to be considered in the decision process before local prostate radiotherapy. Results from other centres are needed to validate our findings. PMID:23227960

  2. Maximizing dosimetric benefits of IMRT in the treatment of localized prostate cancer through multicriteria optimization planning

    SciTech Connect

    Wala, Jeremiah; Craft, David; Paly, Jon; Zietman, Anthony; Efstathiou, Jason

    2013-10-01

    We examine the quality of plans created using multicriteria optimization (MCO) treatment planning in intensity-modulated radiation therapy (IMRT) in treatment of localized prostate cancer. Nine random cases of patients receiving IMRT to the prostate were selected. Each case was associated with a clinically approved plan created using Corvus. The cases were replanned using MCO-based planning in RayStation. Dose-volume histogram data from both planning systems were presented to 2 radiation oncologists in a blinded evaluation, and were compared at a number of dose-volume points. Both physicians rated all 9 MCO plans as superior to the clinically approved plans (p<10{sup −5}). Target coverage was equivalent (p = 0.81). Maximum doses to the prostate and bladder and the V50 and V70 to the anterior rectum were reduced in all MCO plans (p<0.05). Treatment planning time with MCO took approximately 60 minutes per case. MCO-based planning for prostate IMRT is efficient and produces high-quality plans with good target homogeneity and sparing of the anterior rectum, bladder, and femoral heads, without sacrificing target coverage.

  3. Dynamic contrast-enhanced MRI for prostate cancer localization.

    PubMed

    Jackson, A S N; Reinsberg, S A; Sohaib, S A; Charles-Edwards, E M; Jhavar, S; Christmas, T J; Thompson, A C; Bailey, M J; Corbishley, C M; Fisher, C; Leach, M O; Dearnaley, D P

    2009-02-01

    Radiotherapy dose escalation improves tumour control in prostate cancer but with increased toxicity. Boosting focal tumour only may allow dose escalation with acceptable toxicity. Intensity-modulated radiotherapy can deliver this, but visualization of the tumour remains limiting. CT or conventional MRI techniques are poor at localizing tumour, but dynamic contrast-enhanced MRI (DCE-MRI) may be superior. 18 patients with prostate cancer had T(2) weighted (T2W) and DCE-MRI prior to prostatectomy. The prostate was sectioned meticulously so as to achieve accurate correlation between imaging and pathology. The accuracy of DCE-MRI for cancer detection was calculated by a pixel-by-pixel correlation of quantitative DCE-MRI parameter maps and pathology. In addition, a radiologist interpreted the DCE-MRI and T2W images. The location of tumour on imaging was compared with histology, and the accuracy of DCE-MRI and T2W images was then compared. Pixel-by-pixel comparison of quantitative parameter maps showed a significant difference between the benign peripheral zone and tumour for the parameters K(trans), v(e) and k(ep). Calculation of areas under the receiver operating characteristic curve showed that the pharmacokinetic parameters were only "fair" discriminators between cancer and benign gland. Interpretation of DCE-MRI and T2W images by a radiologist showed DCE-MRI to be more sensitive than T2W images for tumour localization (50% vs 21%; p = 0.006) and similarly specific (85% vs 81%; p = 0.593). The superior sensitivity of DCE-MRI compared with T2W images, together with its high specificity, is arguably sufficient for its use in guiding radiotherapy boosts in prostate cancer.

  4. Estimating Preferences for Treatments in Patients With Localized Prostate Cancer

    SciTech Connect

    Ávila, Mónica; Becerra, Virginia; Guedea, Ferran; Suárez, José Francisco; Fernandez, Pablo; Macías, Víctor; Mariño, Alfonso; and others

    2015-02-01

    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 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. 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

  5. [Clinical to planning target volume margins in prostate cancer radiotherapy].

    PubMed

    Ramiandrisoa, F; Duvergé, L; Castelli, J; Nguyen, T D; Servagi-Vernat, S; de Crevoisier, R

    2016-10-01

    The knowledge of inter- and intrafraction motion and deformations of the intrapelvic target volumes (prostate, seminal vesicles, prostatectomy bed and lymph nodes) as well as the main organs at risk (bladder and rectum) allow to define rational clinical to planning target volume margins, depending on the different radiotherapy techniques and their uncertainties. In case of image-guided radiotherapy, prostate margins and seminal vesicles margins can be between 5 and 10mm. The margins around the prostatectomy bed vary from 10 to 15mm and those around the lymph node clinical target volume between 7 and 10mm. Stereotactic body radiotherapy allows lower margins, which are 3 to 5mm around the prostate. Image-guided and stereotactic body radiotherapy with adequate margins allow finally moderate or extreme hypofractionation. PMID:27614515

  6. [Localized prostate cancer Focal Therapy: "A la carte" Model].

    PubMed

    Linares Espinós, E; Barret, E; Sivaraman, A; Pérez-Reggeti, J I; Sánchez-Salas, R; Rozet, F; Galiano, M; Cathelineau, X

    2016-07-01

    Focal therapy has settled as an alternative to radical treatment in selected cases of localized prostate cancer. The selection of patients who are candidates for focal therapy is based on imaging diagnosis relying on multiparametric MRI and image fusion techniques. Thanks to the oncological results and safety profiles of initial series, various energy sources have been developed over the last years. The availability of multiple types of energy sources for focal therapy, commits us to evaluate what type of energy would be the optimal depending on patient's profile and type of lesion. A unique energy for focal therapy would be ideal, but facing the research of the various types of energy we must identify which one is recommended for each lesion. With the experience of our center in different approaches of focal therapy we propose the "A LA CARTE" MODEL based on localization of the lesion. We present the criteria the "a la carte" model is based on, supported by the published evidence on the use of different ablative therapies for the treatment of localized prostate cancer. Lesion localization, technical characteristics of each type of energy, patient's profile and secondary effects must be considered in every choice of focal therapy. PMID:27416638

  7. Clinical Utility of Prostate Carcinoma Molecular Diagnostic Tests

    PubMed Central

    Shappell, Scott B

    2008-01-01

    Instead of relying on serum prostate-specific antigen (PSA) to identify patients for prostate biopsy, new laboratory tests are needed that have improved specificity for prostate carcinoma (CaP), allow accurate classification of clinically insignificant CaPs, allow for detection of clinically significant CaP in patients without elevated serum PSA, and allow for identification of aggressive forms of CaP, which may warrant adjunctive or even molecularly targeted therapy in the future. Over the last several years, high-throughput gene expression profiling and proteinomics have led to the identification of genes and proteins that are specifically overexpressed in CaP. Molecular diagnostic techniques readily translated to the clinical laboratory have been incorporated into the development of new tests based on these novel molecular alterations in CaP. Some of these tests already have well-documented clinical utility, such as in facilitating prostate biopsy decisions, and are routinely available. The current review focuses on the biological, clinical, and laboratory aspects of the most promising of these current and near-future molecular CaP tests. PMID:18470278

  8. Patient perception of local anesthesia for prostate brachytherapy.

    PubMed

    Smathers, S; Wallner, K; Simpson, C; Roof, J

    2000-05-01

    Prostate brachytherapy is an increasingly popular treatment for early-stage prostate cancer. Until now, spinal or general anesthesia for the procedure has been the standard of care. For patient safety, patient convenience, and to limit use of operating facilities, the authors started performing implants routinely with local anesthesia. We present here an evaluation of patients' acceptance of prostate brachytherapy under local anesthesia. On arrival at our department on the morning of the procedure, the patient is brought into the simulator suite, an intravenous line is started, and a urinary catheter is inserted. With the patient in the lithotomy position, a 5-by-5-cm patch of perineal skin and subcutaneous tissue is anesthetized by local infiltration of 10 mL of 1% lidocaine, using a 25-gauge 5/8-inch needle. Immediately following injection into the subcutaneous tissues, the deeper tissues, including the pelvic floor and prostate apex, are anesthetized by injecting 15 mL lidocaine solution with approximately 8 passes of a 20-gauge 1-inch needle. Following subcutaneous and periapical lidocaine injections, the transrectal ultrasound (TRUS) probe is positioned to reproduce the planning images and a 3.5- or 6-inch, 22-gauge spinal needle is inserted into the peripheral planned needle tracks, monitored by TRUS. When the tips of the needles reach the prostatic base, about 1 mL of lidocaine solution is injected in the intraprostatic track, as the needle is slowly withdrawn. The lidocaine infiltration procedure takes approximately 10 to 15 minutes. Seed implantation is then performed as previously described. At the time of this report preparation, 58 of the 71 patients (81%) were interviewed, with a median follow-up of 6 months since the implant procedure. On a scale of 1 to 10, the median biopsy pain score was 4.5 compared with a median pain score with the implant procedure of 3.0. There was no clear correlation between the two scores (r = .26). There was no correlation

  9. Preclinical and clinical development of DNA vaccines for prostate cancer.

    PubMed

    Colluru, V T; Johnson, Laura E; Olson, Brian M; McNeel, Douglas G

    2016-04-01

    Prostate cancer is the most commonly diagnosed cancer in the United States. It is also the second leading cause of cancer-related death in men, making it one of the largest public health concerns today. Prostate cancer is an ideal disease for immunotherapies because of the generally slow progression, the dispensability of the target organ in the patient population, and the availability of several tissue-specific antigens. As such, several therapeutic vaccines have entered clinical trials, with one autologous cellular vaccine (sipuleucel-T) recently gaining Food and Drug Administration approval after demonstrating overall survival benefit in randomized phase III clinical trials. DNA-based vaccines are safe, economical, alternative "off-the-shelf" approaches that have undergone extensive evaluation in preclinical models. In fact, the first vaccine approved in the United States for the treatment of cancer was a DNA vaccine for canine melanoma. Several prostate cancer-specific DNA vaccines have been developed in the last decade and have shown promising results in early phase clinical trials. This review summarizes anticancer human DNA vaccine trials, with a focus on those conducted for prostate cancer. We conclude with an outline of special considerations important for the development and successful translation of DNA vaccines from the laboratory to the clinic.

  10. Light penetration in the human prostate: a whole prostate clinical study at 763 nm

    NASA Astrophysics Data System (ADS)

    Moore, Caroline M.; Mosse, C. Alexander; Allen, Clare; Payne, Heather; Emberton, Mark; Bown, Stephen G.

    2011-01-01

    Photodynamic therapy (PDT) is being investigated as a treatment for localized prostate cancer. Photodynamic therapy uses a photosensitizing drug which is activated by a specific wavelength of light, in the presence of oxygen. The activated drug reacts with tissue oxygen to produce reactive oxygen species which are responsible for localized tissue necrosis. One of the determinants of the PDT effect is the penetration of light in the prostate. This study assesses the penetration depth of 763 nm light throughout the prostate. Eight men undergoing multiple hollow needle insertion for high dose rate brachytherapy were recruited. 763 nm light, produced by a diode laser, was delivered to the prostate using cylindrically diffusing optical fibers within the plastic needles. Light was detected at different distances from the source, using an isotropic detector within nearby needles. Penetration depth was calculated using the Boltzmann approximation to the diffusion equation. Delivery detector fiber separation was measured on computed tomography. The mean penetration depth was 0.57 cm, but there was within patient variation of a mean factor of 4.3. Further work is ongoing to assess the effect of such variability in light penetration, on the PDT effect.

  11. Kallikrein-Related Peptidases in Prostate Cancer: From Molecular Function to Clinical Application

    PubMed Central

    Fuhrman-Luck, Ruth A.; Loessner, Daniela

    2014-01-01

    Prostate cancer is a leading contributor to male cancer-related deaths worldwide. Kallikrein-related peptidases (KLKs) are serine proteases that exhibit deregulated expression in prostate cancer, with KLK3, or prostate specific antigen (PSA), being the widely-employed clinical biomarker for prostate cancer. Other KLKs, such as KLK2, show promise as prostate cancer biomarkers and, additionally, their altered expression has been utilised for the design of KLK-targeted therapies. There is also a large body of in vitro and in vivo evidence supporting their role in cancer-related processes. Here, we review the literature on studies to date investigating the potential of other KLKs, in addition to PSA, as biomarkers and in therapeutic options, as well as their current known functional roles in cancer progression. Increased knowledge of these KLK-mediated functions, including degradation of the extracellular matrix, local invasion, cancer cell proliferation, interactions with fibroblasts, angiogenesis, migration, bone metastasis and tumour growth in vivo, may help define new roles as prognostic biomarkers and novel therapeutic targets for this cancer.

  12. Is there any association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer?

    PubMed Central

    Doluoglu, Omer Gokhan; Ceylan, Cavit; Kilinc, Fatih; Gazel, Eymen; Resorlu, Berkan; Odabas, Oner

    2016-01-01

    ABSTRACT Purpose We investigated the association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer. Materials and Methods The data of 440 patients who had undergone prostate biopsies due to high PSA levels and suspicious digital rectal examination findings were reviewed retrospectively. The patients were divided into two groups based on the presence of accompanying NIH IV prostatitis. The exclusion criteria were as follows: Gleason score>6, PSA level>20ng/mL, >2 positive cores, >50% cancerous tissue per biopsy, urinary tract infection, urological interventions at least 1 week previously (cystoscopy, urethral catheterization, or similar procedure), history of prostate biopsy, and history of androgen or 5-alpha reductase use. All patient's age, total PSA and free PSA levels, ratio of free to total PSA, PSA density and prostate volume were recorded. Results In total, 101 patients were included in the study. Histopathological examination revealed only PCa in 78 (77.2%) patients and PCa+NIH IV prostatitis in 23 (22.7%) patients. The median total PSA level was 7.4 (3.5–20.0) ng/mL in the PCa+NIH IV prostatitis group and 6.5 (0.6–20.0) ng/mL in the PCa group (p=0.67). The PSA level was≤10ng/mL in 60 (76.9%) patients in the PCa group and in 16 (69.6%) patients in the PCa+NIH IV prostatitis group (p=0.32). Conclusions Our study showed no statistically significant difference in PSA levels between patients with and without NIH IV prostatitis accompanying PCa. PMID:27256190

  13. Update of Dutch Multicenter Dose-Escalation Trial of Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Al-Mamgani, Abrahim Putten, Wim L.J. van; Heemsbergen, Wilma D.; Leenders, Geert J.L.H. van; Slot, Annerie; Dielwart, Michel F.H.; Incrocci, Luca; Lebesque, Joos V.

    2008-11-15

    Purpose: To update the analysis of the Dutch dose-escalation trial of radiotherapy for prostate cancer. Patients and Methods: A total of 669 patients with localized prostate cancer were randomly assigned to receive 68 or 78 Gy. The patients were stratified by age, institution, use of neoadjuvant or adjuvant hormonal therapy, and treatment group. The primary endpoint was freedom from failure (FFF), with failure defined as clinical or biochemical failure. Two definitions of biochemical failure were used: the American Society for Therapeutic Radiology and Oncology definition (three consecutive increases in prostate-specific antigen level) and the Phoenix definition (nadir plus 2 {mu}g/L). The secondary endpoints were freedom from clinical failure, overall survival, and genitourinary and gastrointestinal toxicity. Results: After a median follow-up of 70 months, the FFF using the American Society for Therapeutic Radiology and Oncology definition was significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 54% vs. 47%, respectively; p = 0.04). The FFF using the Phoenix definition was also significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 56% vs. 45%, respectively; p = 0.03). However, no differences in freedom from clinical failure or overall survival were observed. The incidence of late Grade 2 or greater genitourinary toxicity was similar in both arms (40% and 41% at 7 years; p = 0.6). However, the cumulative incidence of late Grade 2 or greater gastrointestinal toxicity was increased in the 78-Gy arm compared with the 68-Gy arm (35% vs. 25% at 7 years; p = 0.04). Conclusion: The results of our study have shown a statistically significant improvement in FFF in prostate cancer patients treated with 78 Gy but with a greater rate of late gastrointestinal toxicity.

  14. A comparison of rigid registration methods for prostate localization on CBCT and the dependence on rectum distension

    NASA Astrophysics Data System (ADS)

    Boydev, C.; Pasquier, D.; Derraz, F.; Peyrodie, L.; Taleb-Ahmed, A.; Thiran, J. P.

    2014-03-01

    We evaluated automatic three-dimensional intensity-based rigid registration (RR) methods for prostate localization on CBCT scans and studied the impact of rectum distension on registration quality. 106 CBCT scans of 9 prostate patients were used. Each one was registered to the planning computed tomography (CT) scan using different methods: (a) global registration, (b) pelvis bony structure registration, (c) bony registration refined by a local prostate registration using the CT clinical target volume (CTV) expanded with 1, 3, 5, 8, 10, 12, 15 or 20-mm margin. Automatic CBCT contours were generated after propagation of the manual CT contours. To evaluate results, a radiation oncologist was asked to manually delineate the CTV on the CBCT scans (gold standard). The Dice similarity coefficients between propagated and manual CBCT contours were calculated.

  15. [Prognostic factors of localised, locally advanced or metastatic prostate cancer].

    PubMed

    Joly, Florence; Henry-Amar, Michel

    2007-07-01

    In prostate cancer, whatever the stage of the disease, the selection of a treatment strategy is based on prognostic factors. Clinical stage, serum PSA concentration and Gleason score are among the most recognised factors. A combination of these three parameters leads to a score used to define prognostic groups that are routinely used in daily practice. More recently, predictive statistical models have been developed that were associated with nomograms. The objective of nomograms is, for a given patient, to calculate his probability to develop disease extension or relapse based on clinical, biological, histological and therapeutic (radiotherapy, hormonotherapy) data. Such nomograms are not all validated and their application in daily practice is more difficult than that of classical prognostic classifications. Nowadays, the progress and accessibility to novel technologies applied to biology will make possible in the near future the assessment of new prognostic profiles based on genetic and/or proteomic tumour characteristics.

  16. Drug and device development for localized prostate cancer: report of a Food and Drug Administration/American Urological Association public workshop.

    PubMed

    Jarow, Jonathan P; Thompson, Ian M; Kluetz, Paul G; Baxley, John; Sridhara, Rajeshwari; Scardino, Peter; Carroll, Peter; Albertsen, Peter; Carter, H Balentine; Brawley, Otis; Sartor, Oliver; Sandler, Howard; Kiefert, James J; Morton, Ronald A

    2014-05-01

    Summary of the discussion at a public workshop cosponsored by the U.S. Food and Drug Administration (FDA) and the American Urological Association reviewing potential trial designs for product and device development for the treatment of localized prostate cancer. Product development for treatment of localized prostate cancer has been stymied by the impracticality of using overall survival as an endpoint in patients with localized disease and the lack of acceptable surrogate endpoints. A workshop evaluating potential trial designs for the development of therapies for localized prostate cancer was held in San Diego, CA, in May 2013. Invited experts represented multiple stakeholders, including urology, medical oncology, radiation oncology, industry, and patient advocates. The expert panel discussed development of products for all risk strata of clinically localized prostate cancer. The panel responded to specific questions from FDA, discussing trial design for patients with low-, intermediate-, and high-risk prostate cancer, focal therapy for prostate cancer, patients who have undergone definitive radiation therapy, and adjuvant therapy for patients undergoing radiation therapy or surgery. Expert commentary provided by the panel will inform a planned FDA guidance on pathways for product and device development for treatment of localized prostate cancer and will be discussed at meetings of the FDA's Oncologic Drugs Advisory Committee. FDA intends to develop a set of principles that can be used to promote the development of new products or devices for the treatment of this disease.

  17. Interactive 3D segmentation of the prostate in magnetic resonance images using shape and local appearance similarity analysis

    NASA Astrophysics Data System (ADS)

    Shahedi, Maysam; Fenster, Aaron; Cool, Derek W.; Romagnoli, Cesare; Ward, Aaron D.

    2013-03-01

    3D segmentation of the prostate in medical images is useful to prostate cancer diagnosis and therapy guidance, but is time-consuming to perform manually. Clinical translation of computer-assisted segmentation algorithms for this purpose requires a comprehensive and complementary set of evaluation metrics that are informative to the clinical end user. We have developed an interactive 3D prostate segmentation method for 1.5T and 3.0T T2-weighted magnetic resonance imaging (T2W MRI) acquired using an endorectal coil. We evaluated our method against manual segmentations of 36 3D images using complementary boundary-based (mean absolute distance; MAD), regional overlap (Dice similarity coefficient; DSC) and volume difference (ΔV) metrics. Our technique is based on inter-subject prostate shape and local boundary appearance similarity. In the training phase, we calculated a point distribution model (PDM) and a set of local mean intensity patches centered on the prostate border to capture shape and appearance variability. To segment an unseen image, we defined a set of rays - one corresponding to each of the mean intensity patches computed in training - emanating from the prostate centre. We used a radial-based search strategy and translated each mean intensity patch along its corresponding ray, selecting as a candidate the boundary point with the highest normalized cross correlation along each ray. These boundary points were then regularized using the PDM. For the whole gland, we measured a mean+/-std MAD of 2.5+/-0.7 mm, DSC of 80+/-4%, and ΔV of 1.1+/-8.8 cc. We also provided an anatomic breakdown of these metrics within the prostatic base, mid-gland, and apex.

  18. Influence of the number of elongated fiducial markers on the localization accuracy of the prostate

    NASA Astrophysics Data System (ADS)

    de Boer, Johan; de Bois, Josien; van Herk, Marcel; Sonke, Jan-Jakob

    2012-10-01

    Implanting fiducial markers for localization purposes has become an accepted practice in radiotherapy for prostate cancer. While many correction strategies correct for translations only, advanced correction protocols also require knowledge of the rotation of the prostate. For this purpose, typically, three or more markers are implanted. Elongated fiducial markers provide more information about their orientation than traditional round or cylindrical markers. Potentially, fewer markers are required. In this study, we evaluate the effect of the number of elongated markers on the localization accuracy of the prostate. To quantify the localization error, we developed a model that estimates, at arbitrary locations in the prostate, the registration error caused by translational and rotational uncertainties of the marker registration. Every combination of one, two and three markers was analysed for a group of 24 patients. The average registration errors at the prostate surface were 0.3-0.8 mm and 0.4-1 mm for registrations on, respectively, three markers and two markers located on different sides of the prostate. Substantial registration errors (2.0-2.2 mm) occurred at the prostate surface contralateral to the markers when two markers were implanted on the same side of the prostate or only one marker was used. In conclusion, there is no benefit in using three elongated markers: two markers accurately localize the prostate if they are implanted at some distance from each other.

  19. Active surveillance for prostate cancer: a narrative review of clinical guidelines.

    PubMed

    Bruinsma, Sophie M; Bangma, Chris H; Carroll, Peter R; Leapman, Michael S; Rannikko, Antti; Petrides, Neophytos; Weerakoon, Mahesha; Bokhorst, Leonard P; Roobol, Monique J

    2016-03-01

    In the past decade active surveillance (AS) of men with localized prostate cancer has become an increasingly popular management option, and a range of clinical guidelines have been published on this topic. Existing guidelines regarding AS for prostate cancer vary widely, but predominantly state that the most suitable patients for AS are those with pretreatment clinical stage T1c or T2 tumours, serum PSA levels <10 ng/ml, biopsy Gleason scores of 6 or less, a maximum of one or two tumour-positive biopsy core samples and/or a maximum of 50% of cancer per core sample. Following initiation of an AS programme, most guidelines recommend serial serum PSA measurements, digital rectal examinations and surveillance biopsies to check for and identify pathological indications of tumour progression. Definitions of disease reclassification and progression differ among guidelines and multiple criteria for initiation of definitive treatment are proposed. The variety of descriptions of criteria for clinically insignificant prostate cancer indicates a lack of consensus on optimal AS and intervention thresholds. A single set of guidelines are needed in order to reduce variations in clinical practice and to optimize clinical decision-making. To enable truly evidence-based guidelines, further research that combines existing evidence, while also gathering information from more long-term studies is needed. PMID:26813955

  20. Anatomic Boundaries of the Clinical Target Volume (Prostate Bed) After Radical Prostatectomy

    SciTech Connect

    Wiltshire, Kirsty L.; Brock, Kristy K.; Haider, Masoom A.; Zwahlen, Daniel; Kong, Vickie; Chan, Elisa; Moseley, Joanne; Bayley, Andrew; Catton, Charles; Chung, Peter W.M.; Gospodarowicz, Mary; Milosevic, Michael; Kneebone, Andrew; Warde, Padraig; Menard, Cynthia

    2007-11-15

    Purpose: We sought to derive and validate an interdisciplinary consensus definition for the anatomic boundaries of the postoperative clinical target volume (CTV, prostate bed). Methods and Materials: Thirty one patients who had planned for radiotherapy after radical prostatectomy were enrolled and underwent computed tomography and magnetic resonance imaging (MRI) simulation prior to radiotherapy. Through an iterative process of consultation and discussion, an interdisciplinary consensus definition was derived based on a review of published data, patterns of local failure, surgical practice, and radiologic anatomy. In validation, we analyzed the distribution of surgical clips in reference to the consensus CTV and measured spatial uncertainties in delineating the CTV and vesicourethral anastomosis. Clinical radiotherapy plans were retrospectively evaluated against the consensus CTV (prostate bed). Results: Anatomic boundaries of the consensus CTV (prostate bed) are described. Surgical clips (n = 339) were well distributed throughout the CTV. The vesicourethral anastomosis was accurately localized using central sagittal computed tomography reconstruction, with a mean {+-} standard deviation uncertainty of 1.8 {+-} 2.5 mm. Delineation uncertainties were small for both MRI and computed tomography (mean reproducibility, 0-3.8 mm; standard deviation, 1.0-2.3); they were most pronounced in the anteroposterior and superoinferior dimensions and at the superior/posterior-most aspect of the CTV. Retrospectively, the mean {+-} standard deviation CTV (prostate bed) percentage of volume receiving 100% of prescribed dose was only 77% {+-} 26%. Conclusions: We propose anatomic boundaries for the CTV (prostate bed) and present evidence supporting its validity. In the absence of gross recurrence, the role of MRI in delineating the CTV remains to be confirmed. The CTV is larger than historically practiced at our institution and should be encompassed by a microscopic tumoricidal dose.

  1. The prostatic acid phosphatase (ACPP) gene is localized to human chromosome 3q21-q23

    SciTech Connect

    Li, S.S.L.; Sharief, F.S. )

    1993-09-01

    Human prostatic acid phosphatase (ACPP) has been used as a diagnostic marker for prostate cancer. It is synthesized under androgen regulation and secreted by the epithelial cells of the prostate gland. The authors have confirmed the previous assignment of the ACPP gene to chromosome 3 by probing a panel of 25 human-Chinese hamster somatic cell hybrids, and they have further localized the ACPP gene to chromosome 3q21-q23 by fluorescence in situ hybridization. 10 refs., 1 fig.

  2. Economic analysis of a phase III clinical trial evaluating the addition of total androgen suppression to radiation versus radiation alone for locally advanced prostate cancer (Radiation Therapy Oncology Group protocol 86-10)

    SciTech Connect

    Konski, Andre . E-mail: a_konski@fccc.edu; Sherman, Eric; Krahn, Murray; Bremner, Karen; Beck, J. Robert; Watkins-Bruner, Deborah; Pilepich, Michael

    2005-11-01

    Purpose: To evaluate the cost-effectiveness of adding hormone therapy to radiation for patients with locally advanced prostate cancer, using a Monte Carlo simulation of a Markov Model. Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 86-10 randomized patients to receive radiation therapy (RT) alone or RT plus total androgen suppression (RTHormones) 2 months before and during RT for the treatment of locally advanced prostate cancer. A Markov model was designed with Data Pro (TreeAge Software, Williamstown, MA). The analysis took a payer's perspective. Transition probabilities from one state of health (i.e., with no disease progression or with hormone-responsive metastatic disease) to another were calculated from published rates pertaining to RTOG 86-10. Patients remained in one state of health for 1 year. Utility values for each health state and treatment were obtained from the literature. Distributions were sampled at random from the treatment utilities according to a second-order Monte Carlo simulation technique. Results: The mean expected cost for the RT-only treatments was $29,240 (range, $29,138-$29,403). The mean effectiveness for the RT-only treatment was 5.48 quality-adjusted life years (QALYs) (range, 5.47-5.50). The mean expected cost for RTHormones was $31,286 (range, $31,058-$31,555). The mean effectiveness was 6.43 QALYs (range, 6.42-6.44). Incremental cost-effectiveness analysis showed RTHormones to be within the range of cost-effectiveness at $2,153/QALY. Cost-effectiveness acceptability curve analysis resulted in a >80% probability that RTHormones is cost-effective. Conclusions: Our analysis shows that adding hormonal treatment to RT improves health outcomes at a cost that is within the acceptable cost-effectiveness range.

  3. An arranged marriage for precision medicine: hypoxia and genomic assays in localized prostate cancer radiotherapy.

    PubMed

    Bristow, R G; Berlin, A; Dal Pra, A

    2014-03-01

    Prostate cancer (CaP) is the most commonly diagnosed malignancy in males in the Western world with one in six males diagnosed in their lifetime. Current clinical prognostication groupings use pathologic Gleason score, pre-treatment prostatic-specific antigen and Union for International Cancer Control-TNM staging to place patients with localized CaP into low-, intermediate- and high-risk categories. These categories represent an increasing risk of biochemical failure and CaP-specific mortality rates, they also reflect the need for increasing treatment intensity and justification for increased side effects. In this article, we point out that 30-50% of patients will still fail image-guided radiotherapy or surgery despite the judicious use of clinical risk categories owing to interpatient heterogeneity in treatment response. To improve treatment individualization, better predictors of prognosis and radiotherapy treatment response are needed to triage patients to bespoke and intensified CaP treatment protocols. These should include the use of pre-treatment genomic tests based on DNA or RNA indices and/or assays that reflect cancer metabolism, such as hypoxia assays, to define patient-specific CaP progression and aggression. More importantly, it is argued that these novel prognostic assays could be even more useful if combined together to drive forward precision cancer medicine for localized CaP.

  4. An arranged marriage for precision medicine: hypoxia and genomic assays in localized prostate cancer radiotherapy

    PubMed Central

    Berlin, A; Dal Pra, A

    2014-01-01

    Prostate cancer (CaP) is the most commonly diagnosed malignancy in males in the Western world with one in six males diagnosed in their lifetime. Current clinical prognostication groupings use pathologic Gleason score, pre-treatment prostatic-specific antigen and Union for International Cancer Control-TNM staging to place patients with localized CaP into low-, intermediate- and high-risk categories. These categories represent an increasing risk of biochemical failure and CaP-specific mortality rates, they also reflect the need for increasing treatment intensity and justification for increased side effects. In this article, we point out that 30–50% of patients will still fail image-guided radiotherapy or surgery despite the judicious use of clinical risk categories owing to interpatient heterogeneity in treatment response. To improve treatment individualization, better predictors of prognosis and radiotherapy treatment response are needed to triage patients to bespoke and intensified CaP treatment protocols. These should include the use of pre-treatment genomic tests based on DNA or RNA indices and/or assays that reflect cancer metabolism, such as hypoxia assays, to define patient-specific CaP progression and aggression. More importantly, it is argued that these novel prognostic assays could be even more useful if combined together to drive forward precision cancer medicine for localized CaP. PMID:24588670

  5. IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy

    PubMed Central

    Li, Dujuan; Kan, Yunzhen; Fu, Fangfang; Wang, Shuhuan; Shi, Ligang; Liu, Jie; Kong, Lingfei

    2015-01-01

    Immunoglobulin G4-related disease (IgG4-RD) is a recently described inflammatory disease involving multiple organs. Prostate involvement with IgG4-RD is very rare. In this report, we describe a case of IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy. This patient was present with urine retention symptoms. MRI and CT examination revealed the prostatic enlargement and the multiple lymphadenopathy. Serum IgG4 levels were elevated. Prostatic tissue samples resected both this time and less than 1 year earlier showed the same histological type of prostatitis with histopathologic and immunohistochemical findings characteristic of IgG4-RD. The right submandibular lymph nodes excised 2 years earlier were eventually proven to be follicular hyperplasia-type IgG4-related lymphadenopathy. This is the first case of IgG4-RD that began as localized IgG4-related lymphadenopathy and progressed into a systemic disease involving prostate and multiple lymph nodes. This patient showed a good response to steroid therapy. This leads us to advocate a novel pathogenesis of prostatitis, and a novel therapeutic approach against prostatitis. Pathologists and urologists should consider this disease entity in the patients with elevated serum IgG4 levels and the symptoms of prostatic hyperplasia to avoid ineffective medical or unnecessary surgical treatment. PMID:26617921

  6. Locally Advanced Prostate Cancer: Three-Dimensional Magnetic Resonance Spectroscopy to Monitor Prostate Response to Therapy

    SciTech Connect

    Valentini, Anna Lia; Gui, Benedetta; D'Agostino, Giuseppe Roberto; Mattiucci, Giancarlo; Clementi, Valeria; Di Molfetta, Ippolita Valentina; Bonomo, Pierluigi; Mantini, Giovanna

    2012-11-01

    Purpose: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels and time since external beam irradiation (EBRT) in patients treated with long-term hormone therapy (HT) and EBRT for locally advanced disease to verify successful treatment by documenting the achievement of metabolic atrophy (MA). Methods and Materials: Between 2006 and 2008, 109 patients were consecutively enrolled. MA was assessed by choline and citrate peak area-to-noise-ratio <5:1. Cancerous metabolism (CM) was defined by choline-to-creatine ratio >1.5:1 or choline signal-to-noise-ratio >5:1. To test the strength of association between MRSI results and the time elapsed since EBRT (TEFRT), PSA levels, Gleason score (GS), and stage, logistic regression (LR) was performed. p value <0.05 was statistically significant. The patients' outcomes were verified in 2011. Results: MRSI documented MA in 84 of 109 and CM in 25 of 109 cases. LR showed that age, GS, stage, and initial and recent PSA had no significant impact on MRSI results which were significantly related to PSA values at the time of MRSI and to TEFRT. Patients were divided into three groups according to TEFRT: <1 year, 1-2 years, and >2 years. MA was detected in 54.1% of patients of group 1, 88.9% of group 2, and in 94.5% of group 3 (100% when PSA nadir was reached). CM was detected in 50% of patients with reached PSA nadir in group 1. Local relapse was found in 3 patients previously showing CM at long TEFRT. Conclusion: MA detection, indicative of successful treatment because growth of normal or abnormal cells cannot occur without metabolism, increases with decreasing PSA levels and increasing time on HT after EBRT. This supports long-term HT in advanced prostate cancer. Larger study series are needed to assess whether MRSI could predict local relapse by detecting CM at long TEFRT.

  7. SU-D-9A-06: 3D Localization of Neurovascular Bundles Through MR-TRUS Registration in Prostate Radiotherapy

    SciTech Connect

    Yang, X; Rossi, P; Ogunleye, T; Jani, A; Curran, W; Liu, T

    2014-06-01

    Purpose: Erectile dysfunction (ED) is the most common complication of prostate-cancer radiotherapy (RT) and the major mechanism is radiation-induced neurovascular bundle (NVB) damage. However, the localization of the NVB remains challenging. This study's purpose is to accurately localize 3D NVB by integrating MR and transrectal ultrasound (TRUS) images through MR-TRUS fusion. Methods: T1 and T2-weighted MR prostate images were acquired using a Philips 1.5T MR scanner and a pelvic phase-array coil. The 3D TRUS images were captured with a clinical scanner and a 7.5 MHz biplane probe. The TRUS probe was attached to a stepper; the B-mode images were captured from the prostate base to apex at a 1-mm step and the Doppler images were acquired in a 5-mm step. The registration method modeled the prostate tissue as an elastic material, and jointly estimated the boundary condition (surface deformation) and the volumetric deformations under elastic constraint. This technique was validated with a clinical study of 7 patients undergoing RT treatment for prostate cancer. The accuracy of our approach was assessed through the locations of landmarks, as well as previous ultrasound Doppler images of patients. Results: MR-TRUS registration was successfully performed for all patients. The mean displacement of the landmarks between the post-registration MR and TRUS images was 1.37±0.42 mm, which demonstrated the precision of the registration based on the biomechanical model; and the NVB volume Dice Overlap Coefficient was 92.1±3.2%, which demonstrated the accuracy of the NVB localization. Conclusion: We have developed a novel approach to improve 3D NVB localization through MR-TRUS fusion for prostate RT, demonstrated its clinical feasibility, and validated its accuracy with ultrasound Doppler data. This technique could be a useful tool as we try to spare the NVB in prostate RT, monitor NBV response to RT, and potentially improve post-RT potency outcomes.

  8. A comprehensive review of contemporary role of local treatment of the primary tumor and/or the metastases in metastatic prostate cancer.

    PubMed

    Aoun, Fouad; Peltier, Alexandre; van Velthoven, Roland

    2014-01-01

    To provide an overview of the currently available literature regarding local control of primary tumor and oligometastases in metastatic prostate cancer and salvage lymph node dissection of clinical lymph node relapse after curative treatment of prostate cancer. Evidence Acquisition. A systematic literature search was conducted in 2014 to identify abstracts, original articles, review articles, research articles, and editorials relevant to the local control in metastatic prostate cancer. Evidence Synthesis. Local control of primary tumor in metastatic prostate cancer remains experimental with low level of evidence. The concept is supported by a growing body of genetic and molecular research as well as analogy with other cancers. There is only one retrospective observational population based study showing prolonged survival. To eradicate oligometastases, several options exist with excellent local control rates. Stereotactic body radiotherapy is safe, well tolerated, and efficacious treatment for lymph node and bone lesions. Both biochemical and clinical progression are slowed down with a median time to initiate ADT of 2 years. Salvage lymph node dissection is feasible in patients with clinical lymph node relapse after local curable treatment. Conclusion. Despite encouraging oncologic midterm results, a complete cure remains elusive in metastatic prostate cancer patients. Further advances in imaging are crucial in order to rapidly evolve beyond the proof of concept. PMID:25485280

  9. Iterative normalization method for improved prostate cancer localization with multispectral magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Liu, Xin; Samil Yetik, Imam

    2012-04-01

    Use of multispectral magnetic resonance imaging has received a great interest for prostate cancer localization in research and clinical studies. Manual extraction of prostate tumors from multispectral magnetic resonance imaging is inefficient and subjective, while automated segmentation is objective and reproducible. For supervised, automated segmentation approaches, learning is essential to obtain the information from training dataset. However, in this procedure, all patients are assumed to have similar properties for the tumor and normal tissues, and the segmentation performance suffers since the variations across patients are ignored. To conquer this difficulty, we propose a new iterative normalization method based on relative intensity values of tumor and normal tissues to normalize multispectral magnetic resonance images and improve segmentation performance. The idea of relative intensity mimics the manual segmentation performed by human readers, who compare the contrast between regions without knowing the actual intensity values. We compare the segmentation performance of the proposed method with that of z-score normalization followed by support vector machine, local active contours, and fuzzy Markov random field. Our experimental results demonstrate that our method outperforms the three other state-of-the-art algorithms, and was found to have specificity of 0.73, sensitivity of 0.69, and accuracy of 0.79, significantly better than alternative methods.

  10. In vivo MRI based prostate cancer localization with random forests and auto-context model.

    PubMed

    Qian, Chunjun; Wang, Li; Gao, Yaozong; Yousuf, Ambereen; Yang, Xiaoping; Oto, Aytekin; Shen, Dinggang

    2016-09-01

    Prostate cancer is one of the major causes of cancer death for men. Magnetic resonance (MR) imaging is being increasingly used as an important modality to localize prostate cancer. Therefore, localizing prostate cancer in MRI with automated detection methods has become an active area of research. Many methods have been proposed for this task. However, most of previous methods focused on identifying cancer only in the peripheral zone (PZ), or classifying suspicious cancer ROIs into benign tissue and cancer tissue. Few works have been done on developing a fully automatic method for cancer localization in the entire prostate region, including central gland (CG) and transition zone (TZ). In this paper, we propose a novel learning-based multi-source integration framework to directly localize prostate cancer regions from in vivo MRI. We employ random forests to effectively integrate features from multi-source images together for cancer localization. Here, multi-source images include initially the multi-parametric MRIs (i.e., T2, DWI, and dADC) and later also the iteratively-estimated and refined tissue probability map of prostate cancer. Experimental results on 26 real patient data show that our method can accurately localize cancerous sections. The higher section-based evaluation (SBE), combined with the ROC analysis result of individual patients, shows that the proposed method is promising for in vivo MRI based prostate cancer localization, which can be used for guiding prostate biopsy, targeting the tumor in focal therapy planning, triage and follow-up of patients with active surveillance, as well as the decision making in treatment selection. The common ROC analysis with the AUC value of 0.832 and also the ROI-based ROC analysis with the AUC value of 0.883 both illustrate the effectiveness of our proposed method. PMID:27048995

  11. The clinical phenotype of hereditary versus sporadic prostate cancer: HPC definition revisited

    PubMed Central

    Cremers, Ruben G.; Aben, Katja K.; van Oort, Inge M.; Sedelaar, J.P. Michiel; Vasen, Hans F.; Vermeulen, Sita H.

    2016-01-01

    BACKGROUND The definition of hereditary prostate cancer (HPC) is based on family history and age at onset. Intuitively, HPC is a serious subtype of prostate cancer but there are only limited data on the clinical phenotype of HPC. Here, we aimed to compare the prognosis of HPC to the sporadic form of prostate cancer (SPC). METHODS HPC patients were identified through a national registry of HPC families in the Netherlands, selecting patients diagnosed from the year 2000 onward (n = 324). SPC patients were identified from the Netherlands Cancer Registry (NCR) between 2003 and 2006 for a population‐based study into the genetic susceptibility of PC (n = 1,664). Detailed clinical data were collected by NCR‐registrars, using a standardized registration form. Follow‐up extended up to the end of 2013. Differences between the groups were evaluated by cross‐tabulations and tested for statistical significance while accounting for familial dependency of observations by GEE. Differences in progression‐free and overall survival were evaluated using χ2 testing with GEE in a proportional‐hazards model. RESULTS HPC patients were on average 3 years younger at diagnosis, had lower PSA values, lower Gleason scores, and more often locally confined disease. Of the HPC patients, 35% had high‐risk disease (NICE‐criteria) versus 51% of the SPC patients. HPC patients were less often treated with active surveillance. Kaplan–Meier 5‐year progression‐free survival after radical prostatectomy was comparable for HPC (78%) and SPC (74%; P = 0.30). The 5‐year overall survival was 85% (95%CI 81–89%) for HPC versus 80% (95%CI 78–82%) for SPC (P = 0.03). CONCLUSIONS HPC has a favorable clinical phenotype but patients more often underwent radical treatment. The major limitation of HPC is the absence of a genetics‐based definition of HPC, which may lead to over‐diagnosis of PC in men with a family history of prostate cancer. The HPC definition should

  12. 11C-Acetate PET/CT Imaging in Localized Prostate Cancer: A study with MRI and Histopathologic Correlation

    PubMed Central

    Mena, Esther; Turkbey, Baris; Mani, Haresh; Adler, Stephen; Valera, Vladimir A.; Bernardo, Marcelino; Shah, Vijay; Pohida, Thomas; McKinney, Yolanda; Kwarteng, Gideon; Daar, Dagane; Lindenberg, Maria L.; Eclarinal, Philip; Wade, Revia; Linehan, W. Marston; Merino, Maria J.; Pinto, Peter A.; Choyke, Peter L.; Kurdziel, Karen A.

    2012-01-01

    This work characterizes the uptake of 11C-Acetate in prostate cancer (PCa), benign prostate hyperplasia (BPH) and normal prostate tissue in comparison with multi-parametric MRI, whole mount histopathology and clinical markers, to evaluate its potential utility for delineating intra-prostatic tumors in a population of patients with localized PCa. METHODS 39 men with presumed localized PCa underwent dynamic/static abdomen-pelvic 11C-Acetate PET/CT for 30-minutes and 3T multi-parametric (MP) MRI prior to prostatectomy. PET/CT images were registered to MRI using pelvic bones for initial rotation-translation, followed by manual adjustments to account for prostate motion and deformation from the MRI endorectal coil. Whole-mount pathology specimens were sectioned using an MRI-based patient specific mold resulting in improved registration between the MRI, PET and pathology. 11C-Acetate PET standardized uptake values were compared with MP-MRI and pathology. RESULTS 11C-Acetate uptake was rapid but reversible, peaking at 3–5 minutes post-injection and reaching a relative plateau at ~10 minutes. The average SUVmax(10–12min) of tumors was significantly higher than that of normal prostate tissue (4.4±2.05, range 1.8–9.2 vs. 2.1±0.94, range 0.7–3.4; p<0.001); however it was not significantly different from benign prostatic hyperplasia (4.8±2.01; range 1.8–8.8). A sector-based comparison with histopathology, including all tumors > 0.5 cm, revealed a sensitivity and specificity of 61.6 % and 80.0 % for 11C-Acetate PET/CT, and 82.3% and 95.1% for MRI, respectively. Considering only tumors >0.9 cm the 11C-Acetate accuracy was comparable to that of MRI. In a small cohort (n=9), 11C-Acetate uptake was independent of fatty acid synthase expression based on immunohistochemistry. CONCLUSION 11C-Acetate PET/CT demonstrates higher uptake in tumor foci than normal prostate tissue; however 11C-Acetate uptake in tumors is similar to BPH nodules. While 11C-Acetate PET/CT is not

  13. Quality assurance for the clinical implementation of kilovoltage intrafraction monitoring for prostate cancer VMAT

    SciTech Connect

    Ng, J. A.; Booth, J. T.; O’Brien, R. T.; Huang, C.-Y.; Keall, P. J.; Colvill, E.; Poulsen, P. R.

    2014-11-01

    Purpose: Kilovoltage intrafraction monitoring (KIM) is a real-time 3D tumor monitoring system for cancer radiotherapy. KIM uses the commonly available gantry-mounted x-ray imager as input, making this method potentially more widely available than dedicated real-time 3D tumor monitoring systems. KIM is being piloted in a clinical trial for prostate cancer patients treated with VMAT (NCT01742403). The purpose of this work was to develop clinical process and quality assurance (QA) practices for the clinical implementation of KIM. Methods: Informed by and adapting existing guideline documents from other real-time monitoring systems, KIM-specific QA practices were developed. The following five KIM-specific QA tests were included: (1) static localization accuracy, (2) dynamic localization accuracy, (3) treatment interruption accuracy, (4) latency measurement, and (5) clinical conditions accuracy. Tests (1)–(4) were performed using KIM to measure static and representative patient-derived prostate motion trajectories using a 3D programmable motion stage supporting an anthropomorphic phantom with implanted gold markers to represent the clinical treatment scenario. The threshold for system tolerable latency is <1 s. The tolerances for all other tests are that both the mean and standard deviation of the difference between the programmed trajectory and the measured data are <1 mm. The (5) clinical conditions accuracy test compared the KIM measured positions with those measured by kV/megavoltage (MV) triangulation from five treatment fractions acquired in a previous pilot study. Results: For the (1) static localization, (2) dynamic localization, and (3) treatment interruption accuracy tests, the mean and standard deviation of the difference are <1.0 mm. (4) The measured latency is 350 ms. (5) For the tests with previously acquired patient data, the mean and standard deviation of the difference between KIM and kV/MV triangulation are <1.0 mm. Conclusions: Clinical process and

  14. Immunocytochemical localization of estrogen receptors in the normal male and female canine urinary tract and prostate

    SciTech Connect

    Schulze, H.; Barrack, E.R.

    1987-11-01

    We have used the monoclonal estrogen receptor (ER) antibody H222Sp gamma to localize ER by immunocytochemistry in frozen sections of the normal canine urinary tract of both sexes and of the normal prostate of the male. Striking regional heterogeneity of ER location was observed. In the urinary tract, specific ER staining was confined to nuclei of the transitional epithelium (mucosa) and subjacent stroma (submucosa) of the prostatic urethra in the male dog and of the proximal urethra in the female dog. In both sexes there was a gradient of ER staining intensity along these urethral segments. In the male, ER staining intensity was highest in the region of the verumontanum. The pattern and intensity of staining were similar in the male prostatic urethra and female proximal urethra, indicating a similar concentration of ER in these tissues, which have the same embryological origin. No specific staining was found in the kidney, ureter, bladder, or distal urethra of either sex. In the normal prostate, specific immunocytochemical ER staining was confined to nuclei of the prostatic stroma and prostatic ductal epithelium. Specific staining intensity appeared to be higher in the periurethral region of the prostate than in the periphery. No specific staining was found in the acinar epithelium of the prostate. Based on overall staining intensity there appeared to be a higher concentration of ER in the urethra than in the prostate. Scatchard analysis of (/sup 3/H)estradiol binding confirmed a similar ER content in the urethra of male and female dogs and a higher ER content in the prostatic urethra than in the prostate itself (P less than 0.001).

  15. NBN gain is predictive for adverse outcome following image-guided radiotherapy for localized prostate cancer

    PubMed Central

    Sykes, Jenna; Zafarana, Gaetano; Chu, Kenneth C.; Ramnarine, Varune R.; Ishkanian, Adrian; Sendorek, Dorota H.S.; Pasic, Ivan; Lam, Wan L.; Jurisica, Igor; van der Kwast, Theo; Milosevic, Michael; Boutros, Paul C.; Bristow, Robert G.

    2014-01-01

    Despite the use of clinical prognostic factors (PSA, T-category and Gleason score), 20-60% of localized prostate cancers (PCa) fail primary local treatment. Herein, we determined the prognostic importance of main sensors of the DNA damage response (DDR): MRE11A, RAD50, NBN, ATM, ATR and PRKDC. We studied copy number alterations in DDR genes in localized PCa treated with image-guided radiotherapy (IGRT; n=139) versus radical prostatectomy (RadP; n=154). In both cohorts, NBN gains were the most frequent genomic alteration (14.4 and 11% of cases, respectively), and were associated with overall tumour genomic instability (p<0.0001). NBN gains were the only significant predictor of 5yrs biochemical relapse-free rate (bRFR) following IGRT (46% versus 77%; p=0.00067). On multivariate analysis, NBN gain remained a significant independent predictor of bRFR after adjusting for known clinical prognostic variables (HR=3.28, 95% CI 1.56–6.89, Wald p-value=0.0017). No DDR-sensing gene was prognostic in the RadP cohort. In vitro studies correlated NBN gene overexpression with PCa cells radioresistance. In conclusion, NBN gain predicts for decreased bRFR in IGRT, but not in RadP patients. If validated independently, Nibrin gains may be the first PCa predictive biomarker to facilitate local treatment decisions using precision medicine approaches with surgery or radiotherapy. PMID:25415046

  16. Prostate cancer proteomics: The urgent need for clinically validated biomarkers.

    PubMed

    Evans, Caroline A; Glen, Adam; Eaton, Colby L; Larré, Stéphane; Catto, James W F; Hamdy, Freddie C; Wright, Phillip C; Rehman, Ishtiaq

    2009-02-01

    Prostate cancer (PCa) is the most common cancer diagnosis and the second most common cause of cancer-related deaths in men. Currently, serum prostate-specific antigen (PSA) is the only biomarker widely used in the diagnosis and management of patients with PCa. However, PSA lacks diagnostic sensitivity and specificity, leading to false-negative and false-positive test results. PSA cannot distinguish indolent from aggressive disease, leading to many patients being over-treated with associated side-effects. Furthermore, PSA is unable to identify which tumors are likely to become unresponsive to treatment at an early stage. Thus, there is an urgent need for clinically validated biomarkers which will improve the diagnosis and management of PCa. Given the heterogeneity of PCa it is likely that a panel of biomarkers will be required. In the quest for PCa biomarkers, a wide range of samples including urine, serum, tissues, and cell lines have been studied using proteomic approaches such as 2-DE, SELDI-TOF, SILAC, ICAT, iTRAQ, and MALDI-IMS. The value of these technologies, and other emerging platforms such as selected reaction monitoring (SRM) and multiple reaction monitoring (MRM), are discussed in the context of biomarker discovery, validation and addressing the "bottle-necks" that exist prior to clinical translation. PMID:26238619

  17. Korean clinical practice guideline for benign prostatic hyperplasia

    PubMed Central

    Yeo, Jeong Kyun; Choi, Hun; Bae, Jae Hyun; Kim, Jae Heon; Yang, Seong Ok; Oh, Chul Young; Cho, Young Sam; Kim, Kyoung Woo

    2016-01-01

    In 2014, the Korean Urological Association organized the Benign Prostatic Hyperplasia Guideline Developing Committee composed of experts in the field of benign prostatic hyperplasia (BPH) with the participation of the Korean Academy of Family Medicine and the Korean Continence Society to develop a Korean clinical practice guideline for BPH. The purpose of this clinical practice guideline is to provide current and comprehensive recommendations for the evaluation and treatment of BPH. The committee developed the guideline mainly by adapting existing guidelines and partially by using the de novo method. A comprehensive literature review was carried out primarily from 2009 to 2013 by using medical search engines including data from Korea. Based on the published evidence, recommendations were synthesized, and the level of evidence of the recommendations was determined by using methods adapted from the 2011 Oxford Centre for Evidence-Based Medicine. Meta-analysis was done for one key question and four recommendations. A draft guideline was reviewed by expert peer reviewers and discussed at an expert consensus meeting until final agreement was achieved. This evidence-based guideline for BPH provides recommendations to primary practitioners and urologists for the diagnosis and treatment of BPH in men older than 40 years. PMID:26966724

  18. Sex steroid receptor expression and localization in benign prostatic hyperplasia varies with tissue compartment.

    PubMed

    Nicholson, Tristan M; Sehgal, Priyanka D; Drew, Sally A; Huang, Wei; Ricke, William A

    2013-01-01

    Androgens and estrogens, acting via their respective receptors, are important in benign prostatic hyperplasia (BPH). The goals of this study were to quantitatively characterize the tissue distribution and staining intensity of androgen receptor (AR) and estrogen receptor-alpha (ERα), and assess cells expressing both AR and ERα, in human BPH compared to normal prostate. A tissue microarray composed of normal prostate and BPH tissue was used and multiplexed immunohistochemistry was performed to detect AR and ERα. We used a multispectral imaging platform for automated scanning, tissue and cell segmentation and marker quantification. BPH specimens had an increased number of epithelial and stromal cells and increased percentage of epithelium. In both stroma and epithelium, the mean nuclear area was decreased in BPH relative to normal prostate. AR expression and staining intensity in epithelial and stromal cells was significantly increased in BPH compared to normal prostate. ERα expression was increased in BPH epithelium. However, stromal ERα expression and staining intensity was decreased in BPH compared to normal prostate. Double positive (AR and ERα) epithelial cells were more prevalent in BPH, and fewer double negative (AR and ERα) stromal and epithelial negative cells were observed in BPH. These data underscore the importance of tissue layer localization and expression of steroid hormone receptors in the prostate. Understanding the tissue-specific hormone action of androgens and estrogens will lead to a better understanding of mechanisms of pathogenesis in the prostate and may lead to better treatment for BPH.

  19. Online updating of context-aware landmark detectors for prostate localization in daily treatment CT images

    SciTech Connect

    Dai, Xiubin; Gao, Yaozong; Shen, Dinggang

    2015-05-15

    Purpose: In image guided radiation therapy, it is crucial to fast and accurately localize the prostate in the daily treatment images. To this end, the authors propose an online update scheme for landmark-guided prostate segmentation, which can fully exploit valuable patient-specific information contained in the previous treatment images and can achieve improved performance in landmark detection and prostate segmentation. Methods: To localize the prostate in the daily treatment images, the authors first automatically detect six anatomical landmarks on the prostate boundary by adopting a context-aware landmark detection method. Specifically, in this method, a two-layer regression forest is trained as a detector for each target landmark. Once all the newly detected landmarks from new treatment images are reviewed or adjusted (if necessary) by clinicians, they are further included into the training pool as new patient-specific information to update all the two-layer regression forests for the next treatment day. As more and more treatment images of the current patient are acquired, the two-layer regression forests can be continually updated by incorporating the patient-specific information into the training procedure. After all target landmarks are detected, a multiatlas random sample consensus (multiatlas RANSAC) method is used to segment the entire prostate by fusing multiple previously segmented prostates of the current patient after they are aligned to the current treatment image. Subsequently, the segmented prostate of the current treatment image is again reviewed (or even adjusted if needed) by clinicians before including it as a new shape example into the prostate shape dataset for helping localize the entire prostate in the next treatment image. Results: The experimental results on 330 images of 24 patients show the effectiveness of the authors’ proposed online update scheme in improving the accuracies of both landmark detection and prostate segmentation

  20. Magnetic resonance microscopy of prostate tissue: How basic science can inform clinical imaging development

    SciTech Connect

    Bourne, Roger

    2013-03-15

    This commentary outlines how magnetic resonance imaging (MRI) microscopy studies of prostate tissue samples and whole organs have shed light on a number of clinical imaging mysteries and may enable more effective development of new clinical imaging methods.

  1. Long-Term Results of an RTOG Phase II Trial (00-19) of External-Beam Radiation Therapy Combined With Permanent Source Brachytherapy for Intermediate-Risk Clinically Localized Adenocarcinoma of the Prostate

    SciTech Connect

    Lawton, Colleen A.; Yan, Yan; Lee, W. Robert; Gillin, Michael; Firat, Selim; Baikadi, Madhava; Crook, Juanita; Kuettel, Michael; Morton, Gerald; Sandler, Howard

    2012-04-01

    Purpose: External-beam radiation therapy combined with low-doserate permanent brachytherapy are commonly used to treat men with localized prostate cancer. This Phase II trial was performed to document late gastrointestinal or genitourinary toxicity as well as biochemical control for this treatment in a multi-institutional cooperative group setting. This report defines the long-term results of this trial. Methods and Materials: All eligible patients received external-beam radiation (45 Gy in 25 fractions) followed 2-6 weeks later by a permanent iodine 125 implant of 108 Gy. Late toxicity was defined by the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme. Biochemical control was defined by the American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus definition and the ASTRO Phoenix definition. Results: One hundred thirty-eight patients were enrolled from 20 institutions, and 131 were eligible. Median follow-up (living patients) was 8.2 years (range, 2.7-9.3 years). The 8-year estimate of late grade >3 genitourinary and/or gastrointestinal toxicity was 15%. The most common grade >3 toxicities were urinary frequency, dysuria, and proctitis. There were two grade 4 toxicities, both bladder necrosis, and no grade 5 toxicities. In addition, 42% of patients complained of grade 3 impotence (no erections) at 8 years. The 8-year estimate of biochemical failure was 18% and 21% by the Phoenix and ASTRO consensus definitions, respectively. Conclusion: Biochemical control for this treatment seems durable with 8 years of follow-up and is similar to high-dose external beam radiation alone or brachytherapy alone. Late toxicity in this multi-institutional trial is higher than reports from similar cohorts of patients treated with high-dose external-beam radiation alone or permanent low-doserate brachytherapy alone, perhaps suggesting further attention to strategies that limit doses to

  2. Validation and clinical utility of prostate cancer biomarkers

    PubMed Central

    Scher, Howard I.; Morris, Michael J.; Larson, Steven; Heller, Glenn

    2013-01-01

    To improve future drug development and patient management for patients with castration-resistant prostate cancer (CRPC), surrogate biomarkers that are linked to relevant outcomes are urgently needed. A biomarker must be measurable, reproducible, linked to relevant clinical outcomes, and demonstrate utility. This is a rapidly evolving area, with recent trials in CRPC incorporating the detection of circulating tumour cells (CTCs), imaging, and patient-reported outcome biomarkers. We discuss the framework for the development of biomarkers for CRPC, including different categories and contexts of use. We also highlight the requirements of analytical validation, the sequence of trials needed for clinical validation and regulatory approval, and the future outlook for imaging and CTC biomarkers. PMID:23459624

  3. Prediction of clinical manifestations of transurethral resection syndrome by preoperative ultrasonographic estimation of prostate weight

    PubMed Central

    2014-01-01

    Background This study aimed to investigate the relationship between preoperative estimated prostate weight on ultrasonography and clinical manifestations of transurethral resection (TUR) syndrome. Methods The records of patients who underwent TUR of the prostate under regional anesthesia over a 6-year period were retrospectively reviewed. TUR syndrome is usually defined as a serum sodium level of < 125 mmol/l combined with clinical cardiovascular or neurological manifestations. This study focused on the clinical manifestations only, and recorded specific central nervous system and cardiovascular abnormalities according to the checklist proposed by Hahn. Patients with and without clinical manifestations of TUR syndrome were compared to determine the factors associated with TUR syndrome. Receiver operating characteristic curve analysis was used to determine the optimal cutoff value of estimated prostate weight for the prediction of clinical manifestations of TUR syndrome. Results This study included 167 patients, of which 42 developed clinical manifestations of TUR syndrome. There were significant differences in preoperative estimated prostate weight, operation time, resected prostate weight, intravenous fluid infusion volume, blood transfusion volume, and drainage of the suprapubic irrigation fluid between patients with and without clinical manifestations of TUR syndrome. The preoperative estimated prostate weight was correlated with the resected prostate weight (Spearman’s correlation coefficient, 0.749). Receiver operator characteristic curve analysis showed that the optimal cutoff value of estimated prostate weight for the prediction of clinical manifestations of TUR syndrome was 75 g (sensitivity, 0.70; specificity, 0.69; area under the curve, 0.73). Conclusions Preoperative estimation of prostate weight by ultrasonography can predict the development of clinical manifestations of TUR syndrome. Particular care should be taken when the estimated prostate

  4. Use of Local {sup 111}In-Capromab Pendetide Scan Results to Predict Outcome After Salvage Radiotherapy for Prostate Cancer

    SciTech Connect

    Koontz, Bridget F. Mouraviev, Vladimir; Johnson, Jeffrey L.; Mayes, Janice; Chen, Stephanie H.; Wong, Terence Z.; Anscher, Mitchell S.; Sun, Leon; Moul, Judd; Polascik, Thomas J.

    2008-06-01

    Purpose: The {sup 111}In-capromab pendetide scan (ProstaScint; Cytogen Corp., Princeton NJ) is approved by the Food and Drug Administration to evaluate increasing prostate-specific antigen (PSA) levels after radical prostatectomy. This study evaluated the role of prostate bed {sup 111}In-capromab pendetide scan findings to predict response to salvage radiotherapy (RT). Methods and Materials: Forty patients who had PSA recurrence after radical prostatectomy and a {sup 111}In-capromab pendetide scan immediately before salvage prostate bed RT (median, 66 Gy) were identified from the Duke Prostate Center database. Patients with distant uptake of capromab pendetide or long-term androgen deprivation therapy were excluded. Median follow-up after salvage RT was 2.7 years. Patient demographic, clinical, and pathologic characteristics; PSA values; and {sup 111}In-capromab pendetide scan results were retrospectively analyzed. A PSA failure after salvage RT was defined as PSA level greater than 0.2 ng/ml. Data were combined with other published results in a secondary pooled analysis of 106 patients. Results: {sup 111}In-Capromab pendetide findings included 20 patients with negative scan results and 20 with locally positive scan results. Two-year progression-free survival rates were 60% for patients with a negative scan result and 74% for those with a locally positive scan result (p = 0.49). Combined analysis did not show a difference in outcome based on local {sup 111}In-capromab pendetide scan result. Conclusion: For patients without distant signal detected by using {sup 111}In-capromab pendetide scan, patients with locally positive scan findings did not have statistically different progression-free survival than those with a negative scan result, suggesting that salvage RT may be successful in patients with either a locally positive or negative {sup 111}In-capromab pendetide scan result.

  5. Extracellular Vesicles in Prostate Cancer: New Future Clinical Strategies?

    PubMed Central

    2014-01-01

    Prostate cancer (PCa) is the most common cancer—excluding skin tumors—in men older than 50 years of age. Over time, the ability to diagnose PCa has improved considerably, mainly due to the introduction of prostate-specific antigen (PSA) in the clinical routine. However, it is important to take into account that although PSA is a highly organ-specific marker, it is not cancer-specific. This shortcoming suggests the need to find new and more specific molecular markers. Several emerging PCa biomarkers have been evaluated or are being assessed for their potential use. There is increasing interest in the prospective use of extracellular vesicles as specific markers; it is well known that the content of vesicles is dependent on their cellular origin and is strongly related to the stimulus that triggers the release of the vesicles. Consequently, the identification of a disease-specific molecule (protein, lipid or RNA) associated with vesicles could facilitate their use as novel biological markers. The present review describes several in vitro studies that demonstrate the role of vesicles in PCa progression and several in vivo studies that highlight the potential use of vesicles as PCa biomarkers. PMID:24707491

  6. Multiparametric MRI for Localized Prostate Cancer: Lesion Detection and Staging

    PubMed Central

    Margolis, Daniel J. A.

    2014-01-01

    Multiparametric MRI of the prostate combines high-resolution anatomic imaging with functional imaging of alterations in normal tissue caused by neoplastic transformation for the identification and characterization of in situ prostate cancer. Lesion detection relies on a systematic approach to the analysis of both anatomic and functional imaging using established criteria for the delineation of suspicious areas. Staging includes visual and functional analysis of the prostate “capsule” to determine if in situ disease is, in fact, organ-confined, as well as the evaluation of pelvic structures including lymph nodes and bones for the detection of metastasis. Although intertwined, the protocol can be optimized depending on whether lesion detection or staging is of the highest priority. PMID:25525600

  7. Evaluation of the Prostate Bed for Local Recurrence After Radical Prostatectomy Using Endorectal Magnetic Resonance Imaging

    SciTech Connect

    Liauw, Stanley L.; Pitroda, Sean P.; Eggener, Scott E.; Stadler, Walter M.; Pelizzari, Charles A.; Vannier, Michael W.; Oto, Aytek

    2013-02-01

    Purpose: To summarize the results of a 4-year period in which endorectal magnetic resonance imaging (MRI) was considered for all men referred for salvage radiation therapy (RT) at a single academic center; to describe the incidence and location of locally recurrent disease in a contemporary cohort of men with biochemical failure after radical prostatectomy (RP), and to identify prognostic variables associated with MRI findings in order to define which patients may have the highest yield of the study. Methods and Materials: Between 2007 and 2011, 88 men without clinically palpable disease underwent eMRI for detectable prostate-specific antigen (PSA) after RP. The median interval between RP and eMRI was 32 months (interquartile range, 14-57 months), and the median PSA level was 0.30 ng/mL (interquartile range, 0.19-0.72 ng/mL). Magnetic resonance imaging scans consisting of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging were evaluated for features consistent with local recurrence. The prostate bed was scored from 0-4, whereby 0 was definitely normal, 1 probably normal, 2 indeterminate, 3 probably abnormal, and 4 definitely abnormal. Local recurrence was defined as having a score of 3-4. Results: Local recurrence was identified in 21 men (24%). Abnormalities were best appreciated on T2-weighted axial images (90%) as focal hypointense lesions. Recurrence locations were perianastomotic (67%) or retrovesical (33%). The only risk factor associated with local recurrence was PSA; recurrence was seen in 37% of men with PSA >0.3 ng/mL vs 13% if PSA {<=}0.3 ng/mL (P<.01). The median volume of recurrence was 0.26 cm{sup 3} and was directly associated with PSA (r=0.5, P=.02). The correlation between MRI-based tumor volume and PSA was even stronger in men with positive margins (r=0.8, P<.01). Conclusions: Endorectal MRI can define areas of local recurrence after RP in a minority of men without clinical evidence of disease, with yield related to PSA

  8. Quality of Life and Toxicity From Passively Scattered and Spot-Scanning Proton Beam Therapy for Localized Prostate Cancer

    SciTech Connect

    Pugh, Thomas J.; Munsell, Mark F.; Choi, Seungtaek; Nguyen, Quyhn Nhu; Mathai, Benson; Zhu, X. Ron; Sahoo, Narayan; Gillin, Michael; Johnson, Jennifer L.; Amos, Richard A.; Dong, Lei; Mahmood, Usama; Kuban, Deborah A.; Frank, Steven J.; Hoffman, Karen E.; McGuire, Sean E.; Lee, Andrew K.

    2013-12-01

    Purpose: To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). Methods and Materials: Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ≥0.5 × baseline standard deviation. The cumulative incidence of modified Radiation Therapy Oncology Group grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. Results: A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ≥2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ≥3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. Conclusion: Both PSPT and SSPT confer low rates of grade ≥2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a

  9. Morbidity and mortality of local failure after definitive therapy for prostate cancer

    SciTech Connect

    Schellhammer, P.F.; Whitmore, R.B. 3d.; Kuban, D.A.; el-Mahdi, A.M.; Ladaga, L.A.

    1989-03-01

    We reviewed our experience with morbidity and mortality associated with clinical local failure after definitive therapy for adenocarcinoma of the prostate by interstitial 125-iodine implantation, external beam radiation therapy or radical prostatectomy. Morbid complications included unilateral ureteral obstruction; bladder obstruction and/or incontinence requiring treatment by transurethral resection, or placement of a urethral or suprapubic catheter; hematuria requiring intervention for clot evacuation or fulguration, and perineal and/or pelvic pain. Lethal complications included bilateral ureteral obstruction or bowel obstruction. We treated 108 patients with 125-iodine, 178 with external beam radiotherapy and 67 with radical prostatectomy. Clinical local failure occurred in 26 per cent of the 125-iodine, 17 per cent of the external beam radiotherapy and 12 per cent of the radical prostatectomy groups. The total incidence of local failure with 125-iodine was statistically higher than for radical prostatectomy. Stage C and poorly differentiated tumors were associated with a statistically higher incidence of local failure compared to lower stage and grade tumors. However, within each stage and grade there was no significant difference in local failure between treatment modalities. There was negligible morbidity or mortality secondary to local failure associated with stage A2, stage B1 or well differentiated tumors regardless of treatment modality. There was no difference in the morbidity and mortality between treatment modalities for stage C or poorly differentiated tumors. However, for stage B2 or moderately differentiated tumors treated by 125-iodine implantation there was a statistically greater incidence of morbidity and mortality than that associated with external beam radiotherapy and radical prostatectomy.

  10. Active surveillance for the management of localized prostate cancer: Guideline recommendations

    PubMed Central

    Morash, Chris; Tey, Rovena; Agbassi, Chika; Klotz, Laurence; McGowan, Tom; Srigley, John; Evans, Andrew

    2015-01-01

    Introduction: The objective is to provide guidance on the role of active surveillance (AS) as a management strategy for low-risk prostate cancer patients and to ensure that AS is offered to appropriate patients assessed by a standardized protocol. Prostate cancer is often a slowly progressive or sometimes non-progressive indolent disease diagnosed at an early stage with localized tumours that are unlikely to cause morbidity or death. Standard active treatments for prostate cancer include radiotherapy (RT) or radical prostatectomy (RP), but the harms from over diagnosis and overtreatment are of a significant concern. AS is increasingly being considered as a management strategy to avoid or delay the potential harms caused by unnecessary radical treatment. Methods: A literature search of MEDLINE, EMBASE, the Cochrane library, guideline databases and relevant meeting proceedings was performed and a systematic review of identified evidence was synthesized to make recommendations relating to the role of AS in the management of localized prostate cancer. Results: No exiting guidelines or reviews were suitable for use in the synthesis of evidence for the recommendations, but 59 reports of primary studies were identified. Due to studies being either non-comparative or heterogeneous, pooled meta-analyses were not conducted. Conclusion: The working group concluded that for patients with low-risk (Gleason score ≤6) localized prostate cancer, AS is the preferred disease management strategy. Active treatment (RP or RT) is appropriate for patients with intermediate-risk (Gleason score 7) localized prostate cancer. For select patients with low-volume Gleason 3+4=7 localized prostate cancer, AS can be considered. PMID:26225165

  11. [Opportunities and risks of 5α reductase inhibitors in the medical management of Active surveillance for localized prostate cancer].

    PubMed

    Linares Espinos, Estefania; Carballido Rodriguez, Joaquin

    2014-06-01

    Active surveillance (AS) as a therapeutic option is already integrated as a primary treatment strategy in low risk localized prostate cancer (PCa). There is a recent interest for the search of therapeutic interventions that result in a delay in the progression of such indolent cancers. The evaluation of the possible implication of 5 ARI drugs in the reduction of the risk of progression of PCa was enacted by the results of the clinical trials PCPT (Prostate Cancer Prevention Trial) and REDUCE (Reduction by Dutasteride of Prostate Cancer Events study). The results of the REDEEM clinical trial (Reduction by Dutasteride of clinical progression events in expectant management trial) revealed a delay in PCa progression favoring Dutasteride in comparison with placebo, being advanced age and PSA Density independent predictive factors for pathologic progression. Evidences regarding the influence of 5 ARIs in the evolution of AS patients come from few studies with limited follow up. Thus, the conclusions probably are far from being consiidered as definitive. PMID:24914845

  12. Prostate Cancer Specificity of PCA3 Gene Testing: Examples from Clinical Practice

    PubMed Central

    Marks, Leonard S; Bostwick, David G

    2008-01-01

    A specific marker for early prostate cancer would fill an important void. In initial evaluations of the prostate cancer antigen 3 (PCA3) gene vis-à-vis serum prostate-specific antigen (PSA) levels, the gene offers great promise. At the cellular level, PCA3 specificity for cancer is nearly perfect because of the gross overexpression of the gene by cancer cells. As a clinical test for early prostate cancer, heightened specificity is also seen in urine containing prostate cells from men with the disease. PCA3 gene testing holds valuable potential in PSA quandary situations: (1) men with elevated PSA levels but no cancer on initial biopsy; (2) men found to have cancer despite normal levels of PSA; (3) men with PSA elevations associated with varying degrees of prostatitis; and (4) men undergoing active surveillance for presumed microfocal disease. PMID:18836536

  13. Joint modelling of longitudinal and multi-state processes: application to clinical progressions in prostate cancer.

    PubMed

    Ferrer, Loïc; Rondeau, Virginie; Dignam, James; Pickles, Tom; Jacqmin-Gadda, Hélène; Proust-Lima, Cécile

    2016-09-30

    Joint modelling of longitudinal and survival data is increasingly used in clinical trials on cancer. In prostate cancer for example, these models permit to account for the link between longitudinal measures of prostate-specific antigen (PSA) and time of clinical recurrence when studying the risk of relapse. In practice, multiple types of relapse may occur successively. Distinguishing these transitions between health states would allow to evaluate, for example, how PSA trajectory and classical covariates impact the risk of dying after a distant recurrence post-radiotherapy, or to predict the risk of one specific type of clinical recurrence post-radiotherapy, from the PSA history. In this context, we present a joint model for a longitudinal process and a multi-state process, which is divided into two sub-models: a linear mixed sub-model for longitudinal data and a multi-state sub-model with proportional hazards for transition times, both linked by a function of shared random effects. Parameters of this joint multi-state model are estimated within the maximum likelihood framework using an EM algorithm coupled with a quasi-Newton algorithm in case of slow convergence. It is implemented under R, by combining and extending mstate and JM packages. The estimation program is validated by simulations and applied on pooled data from two cohorts of men with localized prostate cancer. Thanks to the classical covariates available at baseline and the repeated PSA measurements, we are able to assess the biomarker's trajectory, define the risks of transitions between health states and quantify the impact of the PSA dynamics on each transition intensity. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Word on the Street: Engaging Local Leaders in a Dialogue About Prostate Cancer Among African Americans

    PubMed Central

    Schoenfeld, Elinor R.; Francis, Linda E.

    2016-01-01

    African American men face the highest rates of prostate cancer, yet with no consensus for screening and treatment, making informed health care decisions is difficult. This study aimed to identify approaches to empowering African American men as proactive participants in prostate cancer decision making using an established community–campus partnership employing elements of community-based participatory research methods. Community stakeholders with an interest in, and knowledge about, health care in two local African American communities were recruited and completed key informant interviews (N = 39). Grounded theory coding identified common themes related to prostate cancer knowledge, beliefs, attitudes, and responses to them. Common barriers such as gender roles, fear, and fatalism were identified as barriers to work-up and treatment, and both communities’ inadequate and inaccurate prostate cancer information described as the key problem. To build on community strengths, participants said the change must come from inside these communities, not be imposed from the outside. To accomplish this, they suggested reaching men through women, connecting men to doctors they can trust, making men’s cancer education part of broader health education initiatives designed as fun and inexpensive family entertainment events, and having churches bring community members in to speak on their experiences with cancer. This study demonstrated the success of community engagement to identify not only barriers but also local strengths and facilitators to prostate cancer care in two suburban/rural African American communities. Building collaboratively on community strengths may improve prostate cancer care specifically and health care in general. PMID:25595017

  15. Word on the Street: Engaging Local Leaders in a Dialogue About Prostate Cancer Among African Americans.

    PubMed

    Schoenfeld, Elinor R; Francis, Linda E

    2016-09-01

    African American men face the highest rates of prostate cancer, yet with no consensus for screening and treatment, making informed health care decisions is difficult. This study aimed to identify approaches to empowering African American men as proactive participants in prostate cancer decision making using an established community-campus partnership employing elements of community-based participatory research methods. Community stakeholders with an interest in, and knowledge about, health care in two local African American communities were recruited and completed key informant interviews (N = 39). Grounded theory coding identified common themes related to prostate cancer knowledge, beliefs, attitudes, and responses to them. Common barriers such as gender roles, fear, and fatalism were identified as barriers to work-up and treatment, and both communities' inadequate and inaccurate prostate cancer information described as the key problem. To build on community strengths, participants said the change must come from inside these communities, not be imposed from the outside. To accomplish this, they suggested reaching men through women, connecting men to doctors they can trust, making men's cancer education part of broader health education initiatives designed as fun and inexpensive family entertainment events, and having churches bring community members in to speak on their experiences with cancer. This study demonstrated the success of community engagement to identify not only barriers but also local strengths and facilitators to prostate cancer care in two suburban/rural African American communities. Building collaboratively on community strengths may improve prostate cancer care specifically and health care in general.

  16. The pattern of prostate cancer local recurrence after radiation and salvage cryoablation

    PubMed Central

    Ng, Chee Kwan; Touma, Naji J.; Chalasani, Venu; Moussa, Madeleine; Downey, Donal B.; Chin, Joseph L.

    2011-01-01

    Objective: We assessed the pattern of local recurrence after salvage cryoablation of the prostate, and the impact of local recurrence on intermediate-term outcome. Methods: One hundred twenty-two patients who underwent salvage cryoablation were studied after a mean follow-up of 56 months. Serial prostate biopsy was carried out after cryoablation. The histopathology of prostate biopsies before and after cryoablation were compared. The prognostic value of post-cryoablation biopsy was assessed with the Cox regression method. Results: 23.1% of patients had a positive biopsy for prostate cancer following salvage cryoablation. Most cancer recurrences occurred in the apex (51.5%), base (21.2%) and seminal vesicles (18.2%). The presence of cancer at the base of the prostate was found to be a prognostic factor for eventual biochemical failure. Overall 5-year biochemical disease-free survival (bDFS) was 28%, however patients with cancer at the base of the prostate had a 5-year bDFS of 0%. Conclusion: Cancer recurrences occurred in areas where aggressive freezing was avoided as it might result in serious problems (e.g., urethro-rectal fistula and incontinence). Post-cryoablation biopsies and the location of persistent disease are of prognostic value. PMID:21251474

  17. Low Temperature Plasma: A Novel Focal Therapy for Localized Prostate Cancer?

    PubMed Central

    Hirst, Adam M.; Frame, Fiona M.; Maitland, Norman J.; O'Connell, Deborah

    2014-01-01

    Despite considerable advances in recent years for the focal treatment of localized prostate cancer, high recurrence rates and detrimental side effects are still a cause for concern. In this review, we compare current focal therapies to a potentially novel approach for the treatment of early onset prostate cancer: low temperature plasma. The rapidly evolving plasma technology has the potential to deliver a wide range of promising medical applications via the delivery of plasma-induced reactive oxygen and nitrogen species. Studies assessing the effect of low temperature plasma on cell lines and xenografts have demonstrated DNA damage leading to apoptosis and reduction in cell viability. However, there have been no studies on prostate cancer, which is an obvious candidate for this novel therapy. We present here the potential of low temperature plasma as a focal therapy for prostate cancer. PMID:24738076

  18. The Impact of Definitive Local Therapy for Lymph Node-Positive Prostate Cancer: A Population-Based Study

    SciTech Connect

    Rusthoven, Chad G.; Carlson, Julie A.; Waxweiler, Timothy V.; Raben, David; Dewitt, Peter E.; Crawford, E. David; Maroni, Paul D.; Kavanagh, Brian D.

    2014-04-01

    Purpose: To evaluate the survival outcomes for patients with lymph node-positive, nonmetastatic prostate cancer undergoing definitive local therapy (radical prostatectomy [RP], external beam radiation therapy [EBRT], or both) versus no local therapy (NLT) in the US population in the modern prostate specific antigen (PSA) era. Methods and Materials: The Surveillance, Epidemiology, and End Results database was queried for patients with T1-4N1M0 prostate cancer diagnosed from 1995 through 2005. To allow comparisons of equivalent datasets, patients were analyzed in separate clinical (cN+) and pathologically confirmed (pN+) lymph node-positive cohorts. Kaplan-Meier overall survival (OS) and prostate cancer-specific survival (PCSS) estimates were generated, with accompanying univariate log-rank and multivariate Cox proportional hazards comparisons. Results: A total of 796 cN+ and 2991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT and 57% had NLT. Outcomes for cN+ patients favored EBRT, with 10-year OS rates of 45% versus 29% (P<.001) and PCSS rates of 67% versus 53% (P<.001). Among pN+ patients, 78% underwent local therapy (RP 57%, EBRT 10%, or both 11%) and 22% had NLT. Outcomes for pN+ also favored local therapy, with 10-year OS rates of 65% versus 42% (P<.001) and PCSS rates of 78% versus 56% (P<.001). On multivariate analysis, local therapy in both the cN+ and pN+ cohorts remained independently associated with improved OS and PCSS (all P<.001). Local therapy was associated with favorable hazard ratios across subgroups, including patients aged ≥70 years and those with multiple positive lymph nodes. Among pN+ patients, no significant differences in survival were observed between RP versus EBRT and RP with or without adjuvant EBRT. Conclusions: In this large, population-based cohort, definitive local therapy was associated with significantly improved survival in patients with lymph node-positive prostate cancer.

  19. Variation in Adherence to External Beam Radiotherapy Quality Measures Among Elderly Men With Localized Prostate Cancer

    SciTech Connect

    Bekelman, Justin E. Zelefsky, Michael J.; Jang, Thomas L.; Basch, Ethan M.; Schrag, Deborah

    2007-12-01

    Purpose: To characterize the variation in adherence to quality measures of external beam radiotherapy (EBRT) for localized prostate cancer and its relation to patient and provider characteristics in a population-based, representative sample of U.S. men. Methods and Materials: We evaluated EBRT quality measures proposed by a RAND expert panel of physicians among men aged {>=}65 years diagnosed between 2000 and 2002 with localized prostate cancer and treated with primary EBRT using data from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare program. We assessed the adherence to five EBRT quality measures that were amenable to analysis using SEER-Medicare data: (1) use of conformal RT planning; (2) use of high-energy (>10-MV) photons; (3) use of custom immobilization; (4) completion of two follow-up visits with a radiation oncologist in the year after therapy; and (5) radiation oncologist board certification. Results: Of the 11,674 patients, 85% had received conformal RT planning, 75% had received high-energy photons, and 97% had received custom immobilization. One-third of patients had completed two follow-up visits with a radiation oncologist, although 91% had at least one visit with a urologist or radiation oncologist. Most patients (85%) had been treated by a board-certified radiation oncologist. Conclusions: The overall high adherence to EBRT quality measures masked substantial variation in geography, socioeconomic status in the area of residence, and teaching affiliation of the RT facility. Future research should examine the reasons for the variations in these measures and whether the variation is associated with important clinical outcomes.

  20. Focal partial salvage low-dose-rate brachytherapy for local recurrent prostate cancer after permanent prostate brachytherapy with a review of the literature

    PubMed Central

    Wakumoto, Yoshiaki; Yamaguchi, Nanae; Horie, Shigeo; Sasai, Keisuke

    2016-01-01

    Purpose To investigate the treatment results for focal partial salvage re-implantation against local recurrence after permanent prostate brachytherapy. Material and methods Between January 2010 and September 2015, 12 patients were treated with focal partial salvage re-implantation for local recurrence after low-dose-rate brachytherapy using 125I seeds. The focal clinical target volume (F-CTV) was delineated on positive biopsy areas in a mapping biopsy, combining the cold spots on the post-implant dosimetry for initial brachytherapy. The F-CTV was expanded by 3 mm to create the planning target volume (PTV) as a margin to compensate for uncertainties in image registration and treatment delivery. The prescribed dose to the PTV was 145 Gy. The characteristics and biochemical disease-free survival (BdFS) rates were analyzed. Genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4. Results The median prostate-specific antigen (PSA) level at re-implantation was 4.09 ng/ml (range: 2.91-8.24 ng/ml). The median follow-up time was 56 months (range: 6-74 months). The median RD2cc and UD10 were 63 Gy and 159 Gy, respectively. The 4-year BdFS rate was 78%, which included non-responders. Biochemical recurrence occurred in two patients after 7 and 31 months, respectively. The former was treated with hormonal therapy after biochemical failure, and the latter underwent watchful waiting (PSA at the last follow-up of 53 months: 7.3 ng/ml) at the patient's request. No patients had grade 3 GU/GI toxicities or died after salvage re-implantation. Conclusions The partial salvage low-dose-rate brachytherapy used to treat local recurrence after permanent prostate brachytherapy is well-tolerated, with high biochemical response rates. This treatment can be not only a method to delay chemical castration but also a curative treatment option in cases of local recurrence of prostate carcinoma after seed implantation

  1. Therapeutic vaccines in metastatic castration-resistant prostate cancer: principles in clinical trial design.

    PubMed

    Madan, Ravi A; Mohebtash, Mahsa; Schlom, Jeffrey; Gulley, James L

    2010-01-01

    Although docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer in 2004, additional therapies are still required. Prostate cancer is often slow-growing and expresses many tumor-associated antigens, making it a feasible target for immunotherapy. Several therapeutic cancer vaccines have been developed for prostate cancer, including antigen-presenting-cell-based, vector-based, and whole tumor cell vaccines. Initial trials demonstrated that vaccine approaches have limited toxicity. Clinical trials of targeted biologic therapies have demonstrated that patient selection is vital, and there is preliminary evidence that clinical parameters can be used to encompass metastatic prostate cancer patients who will more probably respond to vaccine treatment. In addition to appropriate patient selection, a successful clinical trial must have an appropriate primary endpoint as well. Three randomized, 'placebo'-controlled studies in metastatic castration-resistant prostate cancer have suggested a clinically significant survival advantage in spite of a lack of improvement in time to progression, implying that overall survival is the ideal endpoint for such trials. Careful examination of data from completed immunotherapy clinical trials in prostate cancer has identified appropriate patient populations and endpoints. Those principles need to be applied to future trial design to properly evaluate prostate cancer vaccines.

  2. Imaging techniques for local recurrence of prostate cancer: for whom, why and how?

    PubMed

    Rouvière, O

    2012-04-01

    Since there are salvage solutions, it is important to detect local recurrence of prostate cancer as early as possible. The first sign is "biochemical failure" in that the prostate specific antigen (PSA) concentration rises again. The definition of biochemical failure varies depending on the initial treatment: PSA greater than 0.2ng/mL after prostatectomy, nadir+2ng/mL after radiotherapy. There is no standardised definition of biochemical failure after cryotherapy, focused ultrasound, or brachytherapy. Magnetic resonance imaging (MRI) (particularly dynamic MRI) can detect local recurrence with good sensitivity. The role of spectroscopy is still under discussion. For the moment, ultrasound techniques are less effective than MRI.

  3. Effect of Increasing Radiation Doses on Local and Distant Failures in Patients With Localized Prostate Cancer

    SciTech Connect

    Kupelian, Patrick A. Ciezki, Jay; Reddy, Chandana A.; Klein, Eric A.; Mahadevan, Arul

    2008-05-01

    Purpose: To study the effect of radiation dose on local failure (LF) and distant metastasis (DM) in prostate cancer patients treated with external beam radiotherapy. Methods and Materials: The study sample consisted of 919 Stage T1-T3N0M0 patients treated with radiotherapy alone. Three separate dose groups were analyzed: <72 Gy (n = 552, median dose, 68.4 Gy), {>=}72 but <82 Gy (n = 215, median dose, 78 Gy), and {>=}82 Gy (n = 152, median dose, 83 Gy). The median follow-up period for all patients and those receiving <72 Gy, {>=}72 but <82 Gy, and {>=}82 Gy was 97, 112, 94, and 65 months, respectively. Results: For all patients, the LF rate at 10 and 15 years was 6% and 13%, respectively. The 7-year LF rate stratified by dose group (<72 Gy, {>=}72 but <82 Gy, and {>=}82 Gy) was 6%, 2%, and 2%, respectively (p 0.012). For all patients, the DM rate at 10 and 15 years was 10% and 17%, respectively. The 7-year DM rate stratified by dose group (<72 Gy, {>=}72 but <82 Gy, and {>=}82 Gy) was 9%, 6%, and 1%, respectively (p = 0.008). Multivariate analysis revealed T stage (p < 0.001), pretreatment prostate-specific antigen level (p = 0.001), Gleason score (p < 0.001), and dose (p = 0.018) to be independent predictors of DM. For all 919 patients, multivariate analysis revealed only Gleason score (p = 0.009) and dose (p 0.004) to be independent predictors of LF. Conclusion: Although the effect of increasing radiation doses has been documented mostly for biochemical failure rates, the results of our study have shown a clear association between greater radiation doses and lower LF and DM rates.

  4. 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

  5. Two year experience with transrectal prostate ultrasound.

    PubMed

    Badalament, R A; York, J P; Drago, J R

    1990-01-01

    During the last two and a half years, transrectal prostate ultrasound has been used extensively at our institution. Three hundred and twenty patients have been evaluated in a double blind fashion as part of a study comparing digital rectal examination and transrectal prostatic ultrasound. Prostate cancer was detected in twenty three patients (7.2%); 13 had palpable nodules (4.1%) and 10 had non-palpable nodules (3.1%). Of the 23 patients, 19 had clinically localized (Stage B) prostate cancer. Clinical and pathologic staging correlated in 15 patients (79%). This compares favorably to clinical staging accuracy of 55% in patients prior to utilization of transrectal prostatic ultrasound.

  6. Targeting bone metastases in prostate cancer: improving clinical outcome.

    PubMed

    Body, Jean-Jacques; Casimiro, Sandra; Costa, Luís

    2015-06-01

    Bone metastases develop in most patients with metastatic castration-resistant prostate cancer (mCRPC). They affect the structural integrity of bone, manifesting as pain and skeletal-related events (SREs), and are the primary cause of patient disability, reduced quality of life (QOL) and death. Understanding the pathophysiology of bone metastases resulted in the development of agents that improve clinical outcome, suggesting that managing both the systemic disease and associated bone events is important. Historically, the treatment of CRPC bone metastases with early radiopharmaceuticals and external beam radiation therapy was largely supportive; however, now, zoledronic acid and denosumab are integral to the therapeutic strategy for mCRPC. These agents substantially reduce skeletal morbidity and improve patient QOL. Radium-223 dichloride is the first bone-targeting agent to show improved survival and reduced pain and symptomatic skeletal events in patients with mCRPC without visceral disease. Five other systemic agents are currently approved for use in mCRPC based on their ability to improve survival. These include the cytotoxic drugs docetaxel and cabazitaxel, the hormone-based therapies, abiraterone and enzalutamide, and the immunotherapeutic vaccine sipuleucel-T. Abiraterone and enzalutamide are able to reduce SREs and improve survival in this setting. Novel agents targeting tumour and bone cells are under clinical development. PMID:26119830

  7. Outcomes of high-dose intensity-modulated radiotherapy alone with 1 cm planning target volume posterior margin for localized prostate cancer

    PubMed Central

    2013-01-01

    Background Clinically localized prostate cancer may be treated by different approaches of radiation therapy. The aim of this study was to report the results of disease control and toxicity in patients with clinically localized prostate cancer treated with high dose IMRT alone with 1 cm PTV posterior margin. Methods From September 2001 to April 2008, 140 patients with localized prostate cancer were treated with definitive IMRT (dose ≥ 74 Gy) without hormone therapy. Outcomes were measured from the conclusion of radiotherapy. Biochemical failure was defined as PSA nadir + 2.0 ng/dL. Toxicities were assessed using the NCI-CTCAE-version 3.0. Median follow-up was 58 months. Results Biochemical failure occurred in 13.6% of patients. Actuarial 5-year biochemical control rates were 91.7%, 82.5% and 85.9% for low-, intermediate-, and high-risk patients, respectively. Stage T2 patients presented a risk of biochemical failure almost three times higher than stage T1 (RR = 2.91; 95% CI: 1.04; 8.17). Distant metastases occurred in 3 (2%) patients. Five-year metastasis-free and overall survivals were 96% and 97.5%, respectively. Late grade 3 genitourinary and gastrointestinal toxicity rates were, respectively, 1.6% and 3%. Conclusion High-dose IMRT alone with 1 cm posterior PTV margin was effective and safe for patients with localized prostate cancer. PMID:24314072

  8. Pathological Predictors for Site of Local Recurrence After Radiotherapy for Prostate Cancer

    SciTech Connect

    Chopra, Supriya; Toi, Ants; Taback, Nathan; Evans, Andrew; Haider, Masoom A.; Milosevic, Michael; Bristow, Robert G.; Chung, Peter; Bayley, Andrew; Morton, Gerard; Vesprini, Danny; Warde, Padraig; Catton, Charles; Menard, Cynthia

    2012-03-01

    Purpose: Rational design of targeted radiotherapy (RT) in prostate cancer (Pca) hinges on a better understanding of spatial patterns of recurrence. We sought to identify pathological factors predictive for site of local recurrence (LR) after external beam RT. Methods and Materials: Prospective databases were reviewed to identify men with LR after RT from 1997 through 2009. Patients with biochemical failure and biopsy-confirmed Pca more than 2 years after RT were evaluated. Prediction for site of recurrence based on the following pretreatment factors was determined on independent and cluster-sextant basis: presence of malignancy, dominant vs. nondominant percentage core length (PCL) involvement, PCL {>=} or <40%, and Gleason score. Sites of dominant PCL were defined as sextants with peak PCL involvement minus 10%, and >5% for each patient. Results: Forty-one patients with low-intermediate risk Pca constituted the study cohort. Median time to biopsy after RT was 51 months (range, 24-145). Of 246 sextants, 74 were involved with tumor at baseline. When sextants are treated as independent observations the presence of malignancy (77% vs. 22%, p = 0.0001), dominant PCL (90% vs. 46%, p = 0.0001), and PCL {>=}40% (89% vs. 68 %, p = 0.04) were found to be significant predictors for LR, although PCL {>=}40% did not retain statistical significance if sextants were considered correlated. The vast majority of patients (95%) recurred at the original site of dominant PCL or PCL {>=}40%, and 44% also recurred in regions of nondominant PCL <40% (n = 8) and/or benign sampling (n = 14) at baseline. Conclusions: LR after RT predominantly occurs in regions bearing higher histological tumor burden but are not isolated to these sites. Our data highlights the value of spatially resolved baseline pathological sampling and may assist in the design of clinical trials tailoring RT dose prescriptions to subregions of the prostate gland.

  9. Genetic variants of the CYP1B1 gene as predictors of biochemical recurrence after radical prostatectomy in localized prostate cancer patients.

    PubMed

    Gu, Cheng-Yuan; Qin, Xiao-Jian; Qu, Yuan-Yuan; Zhu, Yu; Wan, Fang-Ning; Zhang, Gui-Ming; Sun, Li-Jiang; Zhu, Yao; Ye, Ding-Wei

    2016-07-01

    Clinically localized prostate cancer is curative. Nevertheless many patients suffered from biochemical recurrence (BCR) after radical prostatectomy (RP). Mounting evidence suggest that estrogen and xenobiotic carcinogens play an essential role in progression of prostate cancervia oxidative estrogen metabolism. CYP1B1 is an enzyme involved in the hydroxylation of estrogens, a reaction of key relevance in estrogen metabolism. Given the role of CYP1B1 in the oxidative metabolism of endogenous/exogenous estrogen and compounds, CYP1B1 polymorphisms have the potential to modify its expression and subsequently lead to progression. We hypothesize that genetic variants of the CYP1B1 gene may influence clinical outcome in clinically localized prostate cancer patients. In this cohort study, we genotyped 9 tagging single nucleotide polymorphisms (SNPs) from the CYP1B1 gene in 312 patients treated with RP. For replication, these SNPs were genotyped in an independent cohort of 426 patients. The expression level of CYP1B1 in the adjacent normal prostate tissues was quantified by reverse transcription and real-time polymerase chain reaction. Kaplan-Meier analysis and Cox proportional hazard models were utilized to identify SNPs that correlated with BCR. CYP1B1 rs1056836 was significantly associated with BCR (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.40-0.89, P = 0.002) and relative CYP1B1 mRNA expression. Our findings suggest inherited genetic variation in the CYP1B1 gene may contribute to variable clinical outcomes for patients with clinically localized prostate cancer. PMID:27399092

  10. Intermittent hormone therapy versus continuous hormone therapy for locally advanced prostate cancer: a meta-analysis.

    PubMed

    Dong, ZhiLong; Wang, Hanzhang; Xu, MengMeng; Li, Yang; Hou, MingLi; Wei, YanLing; Liu, Xingchen; Wang, ZhiPing; Xie, XiaoDong

    2015-01-01

    Few randomized studies have compared intermittent hormone therapy (IHT) with continuous hormone therapy (CHT) for the treatment of locally advanced prostate cancer (PCa). Here, we report the results of a meta-analysis of a randomized controlled trial, evaluating the effectiveness of IHT versus CHT for patients with locally advanced PCa. Types of intervention were IHT versus CHT. The primary endpoint of this study is overall mortality and the secondary endpoints are any progression of disease, quality of life (QOL) and adverse effects between two groups. Six randomized controlled trials totaling 2996 patients were included. Results are as follows: after hormone therapy, patients undergoing IHT demonstrated no significant difference from those undergoing CHT in terms of the overall mortality (OR = 1.0, 95% CI [0.86, 1.17]) and disease progression (OR = 1.16, 95% CI [0.86, 1.57]). Men treated with IHT also reported better QOL, fewer adverse effects and considerable economic benefit for the individual and the community. With no difference in overall mortality and incidence of progression, current clinical studies confirm that both therapeutic methods were safe and effective. However, our study also takes into account QOL. When these secondary measures are considered, IHT may be a better option over CHT as patients report a more affordable treatment with improved QOL and fewer adverse effects.

  11. Improved Biochemical Outcomes With Statin Use in Patients With High-Risk Localized Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Kollmeier, Marisa A.; Katz, Matthew S.; Mak, Kimberley; Yamada, Yoshiya; Feder, David J.; Zhang Zhigang; Jia Xiaoyu; Shi Weiji; Zelefsky, Michael J.

    2011-03-01

    Purpose: To investigate the association between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and biochemical and survival outcomes after high-dose radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 1711 men with clinical stage T1-T3 prostate cancer were treated with conformal RT to a median dose of 81 Gy during 1995-2007. Preradiotherapy medication data were available for 1681 patients. Three hundred eighty-two patients (23%) were taking a statin medication at diagnosis and throughout RT. Nine hundred forty-seven patients received a short-course of neoadjuvant and concurrent androgen-deprivation therapy (ADT) with RT. The median follow-up was 5.9 years. Results: The 5- and 8-year PSA relapse-free survival (PRFS) rates for statin patients were 89% and 80%, compared with 83% and 74% for those not taking statins (p = 0.002). In a multivariate analysis, statin use (hazard ratio [HR]0.69, p = 0.03), National Comprehensive Cancer Network (NCCN) low-risk group, and ADT use were associated with improved PRFS. Only high-risk patients in the statin group demonstrated improvement in PRFS (HR 0.52, p = 0.02). Across all groups, statin use was not associated with improved distant metastasis-free survival (DMFS) (p = 0.51). On multivariate analysis, lower NCCN risk group (p = 0.01) and ADT use (p = 0.005) predicted improved DMFS. Conclusions: Statin use during high-dose RT for clinically localized prostate cancer was associated with a significant improvement in PRFS in high-risk patients. These data suggest that statins have anticancer activity and possibly provide radiosensitization when used in conjunction with RT in the treatment of prostate cancer.

  12. Clinical benefits of alpharadin in castrate-chemotherapy-resistant prostate cancer: case report and literature review

    PubMed Central

    Croke, Jennifer; Leung, Eugene; Segal, Roanne; Malone, Shawn

    2012-01-01

    Prostate cancer has the second-highest mortality worldwide in men. The most common site of metastasis is bone. Bone metastases and their resulting complications represent a significant source of morbidity. Radioisotopes have been used for treatment of painful bony metastases. Although shown to decrease pain and analgesia use, this has not improved outcomes. The following case report describes a patient with castrate-resistant prostate cancer who was treated with the radioisotope radium-223 as part of the phase III clinical trial Alpharadin in Patients with Symptomatic Hormone Refractory Prostate Cancer with Skeletal Metastases (ALSYMPCA). He responded to radium-223 with pain relief, bone scan response, stabilisation of prostate specific antigen (PSA) and normalisation of alkaline phosphatase. Interim analysis of this trial has shown that radium-223 significantly prolongs overall survival, time to first skeletal-related event and is well tolerated. Alpharadin is a new treatment option for men with castrate-resistant prostate cancer and symptomatic bone metastases. PMID:23125297

  13. Natural History of Clinically Staged Low- and Intermediate-Risk Prostate Cancer Treated With Monotherapeutic Permanent Interstitial Brachytherapy

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.; Wallner, Kent E.; Butler, Wayne M.

    2010-02-01

    Purpose: To evaluate the natural history of clinically staged low- and intermediate-risk prostate cancer treated with permanent interstitial seed implants as monotherapy. Methods and Materials: Between April 1995 and May 2005, 463 patients with clinically localized prostate cancer underwent brachytherapy as the sole definitive treatment. Men who received supplemental external beam radiotherapy or androgen deprivation therapy were excluded. Dosimetric implant quality was determined based on the minimum dose that covered 90% of the target volume and the volume of the prostate gland receiving 100% of the prescribed dose. Multiple parameters were evaluated as predictors of treatment outcomes. Results: The 12-year biochemical progression-free survival (bPFS), cause-specific survival, and overall survival rates for the entire cohort were 97.1%, 99.7%, and 75.4%, respectively. Only pretreatment prostate-specific antigen level, percent positive biopsy cores, and minimum dose that covered 90% of the target volume were significant predictors of biochemical recurrence. The bPFS, cause-specific survival, and overall survival rates were 97.4%, 99.6%, and 76.2%, respectively, for low-risk patients and 96.4%, 100%, and 74.0%, respectively, for intermediate-risk patients. The bPFS rate was 98.8% for low-risk patients with high-quality implants versus 92.1% for those with less adequate implants (p < 0.01), and it was 98.3% for intermediate-risk patients with high-quality implants versus 86.4% for those with less adequate implants (p < 0.01). Conclusions: High-quality brachytherapy implants as monotherapy can provide excellent outcomes for men with clinically staged low- and intermediate-risk prostate cancer. For these men, a high-quality implant can achieve results comparable to high-quality surgery in the most favorable pathologically staged patient subgroups.

  14. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

    PubMed Central

    Dal Pra, Alan; Locke, Jennifer A.; Borst, Gerben; Supiot, Stephane; Bristow, Robert G.

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  15. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer.

    PubMed

    Dal Pra, Alan; Locke, Jennifer A; Borst, Gerben; Supiot, Stephane; Bristow, Robert G

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  16. Spectrum of mitochondrial genomic variation and associated clinical presentation of prostate cancer in South African men

    PubMed Central

    McCrow, John P.; Petersen, Desiree C.; Louw, Melanie; Chan, Eva K. F.; Harmeyer, Katherine; Vecchiarelli, Stefano; Lyons, Ruth J.; Bornman, M. S. Riana

    2015-01-01

    BACKGROUND Prostate cancer incidence and mortality rates are significantly increased in African–American men, but limited studies have been performed within Sub–Saharan African populations. As mitochondria control energy metabolism and apoptosis we speculate that somatic mutations within mitochondrial genomes are candidate drivers of aggressive prostate carcinogenesis. METHODS We used matched blood and prostate tissue samples from 87 South African men (77 with African ancestry) to perform deep sequencing of complete mitochondrial genomes. Clinical presentation was biased toward aggressive disease (Gleason score >7, 64%), and compared with men without prostate cancer either with or without benign prostatic hyperplasia. RESULTS We identified 144 somatic mtDNA single nucleotide variants (SNVs), of which 80 were observed in 39 men presenting with aggressive disease. Both the number and frequency of somatic mtDNA SNVs were associated with higher pathological stage. CONCLUSIONS Besides doubling the total number of somatic PCa‐associated mitochondrial genome mutations identified to date, we associate mutational load with aggressive prostate cancer status in men of African ancestry. Prostate 76:349–358, 2016. © 2015 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID:26660354

  17. Validation of Novel Biomarkers for Prostate Cancer Progression by the Combination of Bioinformatics, Clinical and Functional Studies

    PubMed Central

    Väänänen, Riina-Minna; Mattsson, Jesse; Li, Yifeng; Tallgrén, Terhi; Tong Ochoa, Natalia; Bjartell, Anders; Åkerfelt, Malin; Taimen, Pekka; Boström, Peter J.

    2016-01-01

    The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clinical, functional or mechanistic relevance in disease progression. In this study, we have used a broad, bioinformatics-based approach to identify such biomarkers across a spectrum of progression stages, including normal and tumor-adjacent, premalignant, primary and late stage lesions. Bioinformatics data mining combined with clinical validation of biomarkers by sensitive, quantitative reverse-transcription PCR (qRT-PCR), followed by functional evaluation of candidate genes in disease-relevant processes, such as cancer cell proliferation, motility and invasion. From 300 initial candidates, eight genes were selected for validation by several layers of data mining and filtering. For clinical validation, differential mRNA expression of selected genes was measured by qRT-PCR in 197 clinical prostate tissue samples including normal prostate, compared against histologically benign and cancerous tissues. Based on the qRT-PCR results, significantly different mRNA expression was confirmed in normal prostate versus malignant PCa samples (for all eight genes), but also in cancer-adjacent tissues, even in the absence of detectable cancer cells, thus pointing to the possibility of pronounced field effects in prostate lesions. For the validation of the functional properties of these genes, and to demonstrate their putative relevance for disease-relevant processes, siRNA knock-down studies were performed in both 2D and 3D organotypic cell culture models. Silencing of three genes (DLX1, PLA2G7 and RHOU) in the prostate cancer cell lines PC3 and VCaP by siRNA resulted in marked growth arrest

  18. Validation of Novel Biomarkers for Prostate Cancer Progression by the Combination of Bioinformatics, Clinical and Functional Studies.

    PubMed

    Alinezhad, Saeid; Väänänen, Riina-Minna; Mattsson, Jesse; Li, Yifeng; Tallgrén, Terhi; Tong Ochoa, Natalia; Bjartell, Anders; Åkerfelt, Malin; Taimen, Pekka; Boström, Peter J; Pettersson, Kim; Nees, Matthias

    2016-01-01

    The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clinical, functional or mechanistic relevance in disease progression. In this study, we have used a broad, bioinformatics-based approach to identify such biomarkers across a spectrum of progression stages, including normal and tumor-adjacent, premalignant, primary and late stage lesions. Bioinformatics data mining combined with clinical validation of biomarkers by sensitive, quantitative reverse-transcription PCR (qRT-PCR), followed by functional evaluation of candidate genes in disease-relevant processes, such as cancer cell proliferation, motility and invasion. From 300 initial candidates, eight genes were selected for validation by several layers of data mining and filtering. For clinical validation, differential mRNA expression of selected genes was measured by qRT-PCR in 197 clinical prostate tissue samples including normal prostate, compared against histologically benign and cancerous tissues. Based on the qRT-PCR results, significantly different mRNA expression was confirmed in normal prostate versus malignant PCa samples (for all eight genes), but also in cancer-adjacent tissues, even in the absence of detectable cancer cells, thus pointing to the possibility of pronounced field effects in prostate lesions. For the validation of the functional properties of these genes, and to demonstrate their putative relevance for disease-relevant processes, siRNA knock-down studies were performed in both 2D and 3D organotypic cell culture models. Silencing of three genes (DLX1, PLA2G7 and RHOU) in the prostate cancer cell lines PC3 and VCaP by siRNA resulted in marked growth arrest

  19. The influence of family history on prostate cancer risk: implications for clinical management.

    PubMed

    Madersbacher, Stephan; Alcaraz, Antonio; Emberton, Mark; Hammerer, Peter; Ponholzer, Anton; Schröder, Fritz H; Tubaro, Andrea

    2011-03-01

    • The most recent evidence for the link between a family history of prostate cancer and individual risk for future disease was examined, with the aim of understanding what the existence and nature of a family history of prostate cancer does to a man's risk of developing the disease. • Our findings highlighted the clear association between a family history of prostate cancer and increased risk of developing the disease; with a greater proximity of relatedness, greater number of family members affected and/or earlier age at diagnosis of the family member elevating risk further. • These findings have important clinical implications for the identification and subsequent management of men deemed to be at increased risk of developing prostate cancer. The evidence for prostate cancer risk reduction with the mono 5α-reductase inhibitor (5ARI) finasteride in a low-risk population and, more recently, with the dual 5ARI dutasteride in a population at increased risk of developing the disease, has potential to expand management options for men at risk of developing prostate cancer beyond more frequent and/or earlier surveillance. • Given that family history can be easily assessed in routine clinical practice, it should be regarded as an important parameter to consider alongside PSA level for prostate cancer risk assessment. PMID:21166744

  20. Variation in Quality of Care Among Older Men with Localized Prostate Cancer

    PubMed Central

    Jayadevappa, Ravishankar; Chhatre, Sumedha; Johnson, Jerry C; Malkowicz, S. Bruce

    2010-01-01

    Background To assess the racial and ethnic disparities in outcomes and their association with process of care measures for Medicare elderly with localized prostate cancer. Methods We used SEER-Medicare databases for the period 1995–2003. African American, non-Hispanic white and Hispanic men with localized prostate cancer were identified and data was obtained for the one year period prior to the diagnosis of prostate cancer and up to eight years of post-diagnosis period. Short-term outcomes were complications, ER visits, readmissions and mortality. Long-term outcomes were prostate cancer-specific and all-cause mortality. Process of care measures were treatment and time to treatment. Cox proportional hazard, logistic and Poisson regressions were used to study the racial and ethnic disparities in outcomes and their association with process of care measures. Results Compared with non-Hispanic white patients, African-American patients (Hazard ration [HR], 1.43; 95% confidence interval [CE], 1.19-1.86) and Hispanic patients (HR=1.39; 95% CI-1.03-1.84) had greater hazard of long term prostate specific mortality. African American patients had higher odds of ER visits (Odds Ratio=1.4, CI=1.2, 1.7) and higher all-cause mortality (HR=1.39, CI=1.3, 1.5) compared to white patients. Time to treatment was longer for African American patients and was indicative of higher hazard of all-cause long-term mortality. Hispanic patients receiving surgery or radiation had higher hazard of long-term prostate-specific mortality compared to white patients receiving hormone therapy. Conclusion Racial and ethnic disparity in outcome is associated with process of care measures (type and time to treatment). There exists opportunity to reduce these disparities by addressing the process of care measures. PMID:24048800

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

    SciTech Connect

    Huang, Yimei Gardner, Stephen J.; Wen, Ning; Zhao, Bo; Gordon, James; Brown, Stephen; Chetty, Indrin J.

    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, followed 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

  2. Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

    ClinicalTrials.gov

    2016-06-06

    Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

  3. Coagulopathy in the prostate cancer patient: prevalence and clinical relevance.

    PubMed Central

    Adamson, A. S.; Francis, J. L.; Witherow, R. O.; Snell, M. E.

    1993-01-01

    Carcinoma of the prostate has historically been associated with the bleeding diathesis which accompanies disseminated intravascular coagulation. We have performed a prospective study into the prevalence of coagulopathy in patients with untreated prostate cancer using matched patients with benign prostatic hypertrophy (BPH) as controls. Haemostatic activation was assessed by measuring fibrinopeptide A (FpA) by an ELISA and D-dimer by a latex agglutination assay. FpA and D-dimer levels were correlated with serum prostate specific antigen (PSA) and bone scan status. Of the cancer patients, 40% had elevated FpA, levels being higher in those with bone scan positive disease (P < 0.05). D-dimer was detectable in 24% of those with prostate cancer but in none with BPH. Neither FpA nor D-dimer were related to serum PSA but D-dimer appeared to be a predictor of bone scan status with a positive predictive value of 91%. It is concluded that changes compatible with subclinical DIC are common in patients presenting with prostate cancer and that measurement of FpA and D-dimer may have roles as tumour markers in this disease. PMID:7682795

  4. Intensity-Modulated Radiotherapy of Pelvic Lymph Nodes in Locally Advanced Prostate Cancer: Planning Procedures and Early Experiences

    SciTech Connect

    Muren, Ludvig Paul Wasbo, Ellen; Helle, Svein Inge; Hysing, Liv Bolstad; Karlsdottir, Asa; Odland, Odd Harald; Valen, Harald; Ekerold, Randi; Johannessen, Dag Clement

    2008-07-15

    Purpose: We present planning and early clinical outcomes of a study of intensity-modulated radiotherapy (IMRT) for locally advanced prostate cancer. Methods and Materials: A total of 43 patients initially treated with an IMRT plan delivering 50 Gy to the prostate, seminal vesicles, and pelvic lymph nodes, followed by a conformal radiotherapy (CRT) plan delivering 20 Gy to the prostate and seminal vesicles, were studied. Dose-volume histogram (DVH) data for the added plans were compared with dose-volume histogram data for the sum of two CRT plans for 15 cases. Gastrointestinal (GI) and genitourinary (GU) toxicity, based on the Radiation Therapy Oncology Group scoring system, was recorded weekly throughout treatment as well as 3 to 18 months after treatment and are presented. Results: Treatment with IMRT both reduced normal tissue doses and increased the minimum target doses. Intestine volumes receiving more than 40 and 50 Gy were significantly reduced (e.g., at 50 Gy, from 81 to 19 cm{sup 3}; p = 0.026), as were bladder volumes above 40, 50, and 60 Gy, rectum volumes above 30, 50, and 60 Gy, and hip joint muscle volumes above 20, 30, and 40 Gy. During treatment, Grade 2 GI toxicity was reported by 12 of 43 patients (28%), and Grade 2 to 4 GU toxicity was also observed among 12 patients (28%). With 6 to 18 months of follow-up, 2 patients (5%) experienced Grade 2 GI effects and 7 patients (16%) experienced Grade 2 GU effects. Conclusions: Use of IMRT for pelvic irradiation in prostate cancer reduces normal tissue doses, improves target coverage, and has a promising toxicity profile.

  5. MRI-guided transurethral ultrasound therapy of the prostate gland: simulations under clinical conditions

    NASA Astrophysics Data System (ADS)

    N'Djin, W. A.; Burtnyk, M.; Kobelevskiy, I.; Bronskill, M.; Chopra, R.

    2011-09-01

    The feasibility of performing MRI-guided transurethral ultrasound therapy in humans has been shown by our group for the treatment of small subvolumes prior to radical prostatectomy. One challenge is to use this technology to treat a volume of tissue equivalent to the entire prostate gland. This simulation study evaluates the feasibility of treating the whole prostate gland and characterizes the nature of the treatment with respect to treatment time, accuracy, and safety. A numerical model was used to simulate a multi-element heating applicator rotating inside the urethra in five human prostates. 3D prostate profiles were segmented from clinical MR images obtained from subjects after insertion of a transurethral heating applicator into the prostate gland. Clinical treatment planning conditions were simulated including device orientation, prostate & rectum geometry, temperature uncertainty, imaging time, and spatial resolution. During ultrasound exposures, acoustic power, frequency and rotation rate were varied based on the prostate radius and on temperature feedback every 5 seconds using MR thermometry. Two treatment approaches (10 or 20 W.cm-2 acoustic power) were tested as well as single and dual-frequency strategies (4.05/13.10 MHz). A 20 W.cm-2 dual-frequency treatment was shown to be the most efficient configuration in achieving full human prostate treatments. Increasing the power from 10 to 20 W.cm-2 led, on average, to treatment times shorter by 50%. Full prostate coagulations were performed in 20.6±1.6 min at a rate of 1.6±0.2 cm3.min-1, and resulted in <8% of undertreated tissue. This configuration succeeded in preserving high-priority critical regions such as the adjacent rectal wall tissues. The principles of prostate thermal therapy using an MR thermometry-guided transurethral ultrasound technique were shown in simulations to be suitable for full gland treatment in prostate geometries derived from human subjects undergoing partial coagulations. Dual

  6. Fast radioactive seed localization in intraoperative cone beam CT for low-dose-rate prostate brachytherapy

    NASA Astrophysics Data System (ADS)

    Hu, Yu-chi; Xiong, Jian-ping; Cohan, Gilad; Zaider, Marco; Mageras, Gig; Zelefsky, Michael

    2013-03-01

    A fast knowledge-based radioactive seed localization method for brachytherapy was developed to automatically localize radioactive seeds in an intraoperative volumetric cone beam CT (CBCT) so that corrections, if needed, can be made during prostate implant surgery. A transrectal ultrasound (TRUS) scan is acquired for intraoperative treatment planning. Planned seed positions are transferred to intraoperative CBCT following TRUS-to-CBCT registration using a reference CBCT scan of the TRUS probe as a template, in which the probe and its external fiducial markers are pre-segmented and their positions in TRUS are known. The transferred planned seeds and probe serve as an atlas to reduce the search space in CBCT. Candidate seed voxels are identified based on image intensity. Regions are grown from candidate voxels and overlay regions are merged. Region volume and intensity variance is checked against known seed volume and intensity profile. Regions meeting the above criteria are flagged as detected seeds; otherwise they are flagged as likely seeds and sorted by a score that is based on volume, intensity profile and distance to the closest planned seed. A graphical interface allows users to review and accept or reject likely seeds. Likely seeds with approximately twice the seed volume are automatically split. Five clinical cases are tested. Without any manual correction in seed detection, the method performed the localization in 5 seconds (excluding registration time) for a CBCT scan with 512×512×192 voxels. The average precision rate per case is 99% and the recall rate is 96% for a total of 416 seeds. All false negative seeds are found with 15 in likely seeds and 1 included in a detected seed. With the new method, updating of calculations of dose distribution during the procedure is possible and thus facilitating evaluation and improvement of treatment quality.

  7. A single nucleotide polymorphism in ADIPOQ predicts biochemical recurrence after radical prostatectomy in localized prostate cancer

    PubMed Central

    Zhang, Guiming; Sun, LiJiang; Zhu, Yao; Ye, Dingwei

    2015-01-01

    Adiponectin has been implicated in prostate cancer (PCa) aggressiveness. However, the role of genetic variations in the adiponectin (ADIPOQ) gene in PCa progression remains unknown. To determine whether genetic variants in ADIPOQ are associated with the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We evaluated three common ADIPOQ polymorphisms in 728 men with clinically localized PCa who underwent RP. Multivariable Cox proportional hazards models and Kaplan–Meier analysis were used to assess their prognostic significance on BCR. The plasma adiponectin concentrations were measured by enzyme-linked immunosorbent assay. ADIPOQ rs182052 variant allele was associated with both increased risk of BCR [HR: 2.44; 95% confidence interval (CI): 1.57–3.79, P = 6×10−5] and decreased adiponectin level (β = −0.048, P = 0.004). Stratified analyses demonstrated that the association was more pronounced in men with higher visceral adipose tissue. Our data support that the ADIPOQ rs182052 SNP may be a predictive biomarker for BCR after RP by a possible mechanism of altering the adiponectin level. If validated, genetic predictors of outcome may help individualizing treatment for PCa. PMID:26320190

  8. A single nucleotide polymorphism in ADIPOQ predicts biochemical recurrence after radical prostatectomy in localized prostate cancer.

    PubMed

    Gu, Chengyuan; Qu, Yuanyuan; Zhang, Guiming; Sun, LiJiang; Zhu, Yao; Ye, Dingwei

    2015-10-13

    Adiponectin has been implicated in prostate cancer (PCa) aggressiveness. However, the role of genetic variations in the adiponectin (ADIPOQ) gene in PCa progression remains unknown. To determine whether genetic variants in ADIPOQ are associated with the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We evaluated three common ADIPOQ polymorphisms in 728 men with clinically localized PCa who underwent RP. Multivariable Cox proportional hazards models and Kaplan-Meier analysis were used to assess their prognostic significance on BCR. The plasma adiponectin concentrations were measured by enzyme-linked immunosorbent assay. ADIPOQ rs182052 variant allele was associated with both increased risk of BCR [HR: 2.44; 95% confidence interval (CI): 1.57-;3.79, P = 6×10-5] and decreased adiponectin level (β = -0.048, P = 0.004). Stratified analyses demonstrated that the association was more pronounced in men with higher visceral adipose tissue. Our data support that the ADIPOQ rs182052 SNP may be a predictive biomarker for BCR after RP by a possible mechanism of altering the adiponectin level. If validated, genetic predictors of outcome may help individualizing treatment for PCa.

  9. Endorectal MRI of Prostate Cancer: Incremental Prognostic Importance of Gross Locally Advanced Disease

    PubMed Central

    Muglia, Valdair F.; Westphalen, Antonio C.; Wang, Zhen J.; Kurhanewicz, John; Carroll, Peter R.; Coakley, Fergus V.

    2013-01-01

    OBJECTIVE The purpose of this study was to determine the frequency and incremental prognostic importance of gross locally advanced disease seen at endorectal MRI in patients with prostate cancer. MATERIALS AND METHODS We retrospectively identified the cases of all patients with biopsy-proven prostate cancer who underwent pretreatment endorectal MRI over a 6-year period (n = 1777). Three experienced radiologists identified by consensus patients with gross locally advanced disease, defined as unequivocal extracapsular extension or unequivocal seminal vesicle invasion. Outcome among these patients was compared with that in a control group without gross locally advanced disease matched by D'Amico risk stratification. RESULTS Sixty-six of 1777 (3.7%) patients had gross locally advanced disease. One of 1085 (0.1%) patients had low-risk disease, 25 of 489 (5.1%) had intermediate-risk disease, and 40 of 203 (19.7%) had high-risk disease. Follow-up data were available for 44 of these 66 patients. During a median follow-up period of 79 months, biochemical failure and metastasis had developed in 17 and 6 of these 44 patients compared with 9 and none of the 65 patients in the control group (p < 0.001). CONCLUSION Almost 4% of patients with prostate cancer, particularly those with intermediate- and high-risk disease, have gross locally advanced disease at endorectal MRI and have a significantly worse prognosis than matched controls. These patients may be candidates for more aggressive treatment. PMID:22109291

  10. Designing normative messages about active surveillance for men with localized prostate cancer

    PubMed Central

    Volk, Robert J.; Kinsman, Gianna T.; Le, Yen-Chi L.; Swank, Paul; Blumenthal-Barby, Jennifer; McFall, Stephanie L.; Byrd, Theresa L.; Mullen, Patricia Dolan; Cantor, Scott B.

    2016-01-01

    Active surveillance (AS) is increasingly recognized as a reasonable option for men with low-risk, localized prostate cancer, yet few men who might benefit from conservative management receive it. We examined the acceptability of normative messages about AS as a management option for patients with low-risk prostate cancer. Men with a diagnosis of localized prostate cancer who were recruited through prostate cancer support organizations completed a web-based survey (N=331). They rated messages about AS for believability, accuracy, and importance for men to hear when making treatment decisions. The message “you don’t have to panic…you have time to think about your options” was perceived as believable, accurate, and important by over 80% of the survivors. In contrast, messages about trust in the AS protocol and “knowing in plenty of time” if treatment is needed were rated as accurate by only about 36% of respondents. For AS to be viewed as a reasonable alternative, men will need reassurance that following an AS protocol is likely to allow time for curative treatment if the cancer progresses. PMID:26066011

  11. Identification of Threshold Prostate Specific Antigen Levels to Optimize the Detection of Clinically Significant Prostate Cancer by Magnetic Resonance Imaging/Ultrasound Fusion Guided Biopsy

    PubMed Central

    Shakir, Nabeel A.; George, Arvin K.; Siddiqui, M. Minhaj; Rothwax, Jason T.; Rais-Bahrami, Soroush; Stamatakis, Lambros; Su, Daniel; Okoro, Chinonyerem; Raskolnikov, Dima; Walton-Diaz, Annerleim; Simon, Richard; Turkbey, Baris; Choyke, Peter L.; Merino, Maria J.; Wood, Bradford J.; Pinto, Peter A.

    2015-01-01

    Purpose Prostate specific antigen sensitivity increases with lower threshold values but with a corresponding decrease in specificity. Magnetic resonance imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and of higher grade than standard 12-core transrectal ultrasound biopsy but the optimal population for its use is not well defined. We evaluated the performance of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across a prostate specific antigen continuum. Materials and Methods We reviewed the records of all patients enrolled in a prospective trial who underwent 12-core transrectal ultrasound and magnetic resonance imaging/ultrasound targeted biopsies from August 2007 through February 2014. Patients were stratified by each of 4 prostate specific antigen cutoffs. The greatest Gleason score using either biopsy method was compared in and across groups as well as across the population prostate specific antigen range. Clinically significant prostate cancer was defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses were performed. Results A total of 1,003 targeted and 12-core transrectal ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a 56.2% detection rate. Targeted biopsy led to significantly more upgrading to clinically significant disease compared to 12-core biopsy. This trend increased more with increasing prostate specific antigen, specifically in patients with prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy, corresponding to 64% of patients who underwent multiparametric magnetic resonance imaging and subsequent fusion biopsy. Conversely a greater proportion of clinically insignificant disease was detected by 12-core vs targeted biopsy overall. These differences persisted when controlling for potential confounders on multivariate analysis. Conclusions Prostate

  12. Stereotactic Body Radiation Therapy for Prostate Cancer: What is the Appropriate Patient-Reported Outcome for Clinical Trial Design?

    PubMed Central

    Woo, Jennifer Ai-Lian; Chen, Leonard N.; Wang, Hongkun; Cyr, Robyn A.; Bhattasali, Onita; Kim, Joy S.; Moures, Rudy; Yung, Thomas M.; Lei, Siyuan; Collins, Brian Timothy; Suy, Simeng; Dritschilo, Anatoly; Lynch, John H.; Collins, Sean P.

    2015-01-01

    Purpose: Stereotactic body radiation therapy (SBRT) is increasingly utilized as primary treatment for clinically localized prostate cancer. Consensus regarding the appropriate patient-reported outcome (PRO) endpoints for clinical trials evaluating radiation modalities for early stage prostate cancer is lacking. To aid in clinical trial design, this study presents PROs over a 36-month period following SBRT for clinically localized prostate cancer. Methods: Between February 2008 and September 2010, 174 hormone-naïve patients with clinically localized prostate cancer were treated with 35–36.25 Gy SBRT (CyberKnife, Accuray) delivered in 5 fractions. Patients completed the validated Expanded Prostate Cancer Index Composite (EPIC)-26 questionnaire at baseline and all follow-ups. The proportion of patients developing a clinically significant decline in each EPIC domain score was determined. The minimally important difference (MID) was defined as a change of one-half the standard deviation from the baseline. Per Radiation Therapy Oncology Group (RTOG) 0938, we also examined the patients who experienced a decline in EPIC urinary domain summary score of >2 points (unacceptable toxicity defined as ≥60% of all patients reporting this degree of decline) and EPIC bowel domain summary score of >5 points (unacceptable toxicity defined as >55% of all patients reporting this degree of decline) from baseline to 1 year. Results: A total of 174 patients at a median age of 69 years received SBRT with a minimum follow-up of 36 months. The proportion of patients reporting a clinically significant decline (MID for urinary/bowel are 5.5/4.4) in EPIC urinary/bowel domain scores was 34%/30% at 6 months, 40%/32.2% at 12 months, and 32.8%/21.5% at 36 months. The patients reporting a decrease in the EPIC urinary domain summary score of >2 points was 43.2% (CI: 33.7%, 54.6%) at 6 months, 51.6% (CI: 43.4%, 59.7%) at 12 months, and 41.8% (CI: 33.3%, 50.6%) at 36 months. The

  13. Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

    PubMed Central

    Mason, Malcolm D.; Parulekar, Wendy R.; Sydes, Matthew R.; Brundage, Michael; Kirkbride, Peter; Gospodarowicz, Mary; Cowan, Richard; Kostashuk, Edmund C.; Anderson, John; Swanson, Gregory; Parmar, Mahesh K.B.; Hayter, Charles; Jovic, Gordana; Hiltz, Andrea; Hetherington, John; Sathya, Jinka; Barber, James B.P.; McKenzie, Michael; El-Sharkawi, Salah; Souhami, Luis; Hardman, P.D. John; Chen, Bingshu E.; Warde, Padraig

    2015-01-01

    Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer. PMID:25691677

  14. Prostate-specific antigen doubling time predicts clinical outcome and survival in prostate cancer patients treated with combined radiation and hormone therapy

    SciTech Connect

    Lee, Andrew K. . E-mail: aklee@mdanderson.org; Levy, Larry B.; Cheung, Rex; Kuban, Deborah

    2005-10-01

    Purpose: To determine whether prostate-specific antigen (PSA) doubling time predicts clinical outcomes in patients with prostate cancer that has been treated with combined radiation and hormone therapy. Methods and Materials: We reviewed the medical records of 621 men with nonmetastatic prostate cancer treated with radiation therapy and hormone therapy between 1989 and 2003. 'Any' clinical failure was defined as any distant, nodal, or local failure, or the use of salvage therapy. 'True' clinical failure was defined as any distant, nodal, or local failure. PSA doubling time was calculated by using the log PSA values from patients with a PSA failure as defined by the American Society of Therapeutic Radiology Oncology consensus statement. One hundred thirty-seven men were at intermediate risk for PSA failure (as determined by T2b, Gleason score of 7, or PSA 10.1-0 ng/mL) and 484 men were at high risk for failure (T2c-4; Gleason 8-10; or PSA >20 ng/mL). Pretreatment PSA value, Gleason score, tumor stage, timing and duration of hormone therapy, radiation therapy dose, and PSA doubling time were analyzed for any associations with time to clinical failure by using Cox regression analysis. Estimates of survival were calculated by using the Kaplan-Meier method. Pairwise comparisons were made by using the log-rank test. Results: Sixty-two men experienced any clinical failure, and 22 men experienced true clinical failure. Multivariate analysis revealed that pretreatment PSA (p = 0.013), Gleason score (p = 0.0019), and a PSA doubling time (PSADT) {<=}8 months (p < 0.001) were independently associated with time to any clinical failure. Tumor stage, hormone therapy timing, hormone therapy duration, and radiation therapy dose were not statistically significant on multivariate or univariate analysis. Only hormone therapy duration (p 0.008) and PSADT {<=}8 months (<0.001) were significantly associated with time to true clinical failure. The estimated 5-year rate of any clinical

  15. Long noncoding RNAs in prostate cancer: overview and clinical implications

    PubMed Central

    Malik, Bhavna; Feng, Felix Y

    2016-01-01

    Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conventional therapy and progresses to castration-resistant prostate cancer (CRPC), which is currently incurable. Thus, there is a critical need to identify biomarkers that will distinguish indolent from aggressive disease, as well as novel therapeutic targets for the prevention or treatment of CRPC. In recent years, long noncoding RNAs (lncRNAs) have emerged as an important class of biological molecules. LncRNAs are polyadenylated RNA species that share many similarities with protein-coding genes despite the fact that they are noncoding (not translated into proteins). They are usually transcribed by RNA polymerase II and exhibit the same epigenetic signatures as protein-coding genes. LncRNAs have also been implicated in the development and progression of variety of cancers, including prostate cancer. While a large number of lncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. In this review, we highlight recent findings on the functional role and molecular mechanisms of lncRNAs in the progression of prostate cancer and evaluate their use as potential biomarkers and therapeutic targets. PMID:27072044

  16. Long noncoding RNAs in prostate cancer: overview and clinical implications.

    PubMed

    Malik, Bhavna; Feng, Felix Y

    2016-01-01

    Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conventional therapy and progresses to castration-resistant prostate cancer (CRPC), which is currently incurable. Thus, there is a critical need to identify biomarkers that will distinguish indolent from aggressive disease, as well as novel therapeutic targets for the prevention or treatment of CRPC. In recent years, long noncoding RNAs (lncRNAs) have emerged as an important class of biological molecules. LncRNAs are polyadenylated RNA species that share many similarities with protein-coding genes despite the fact that they are noncoding (not translated into proteins). They are usually transcribed by RNA polymerase II and exhibit the same epigenetic signatures as protein-coding genes. LncRNAs have also been implicated in the development and progression of variety of cancers, including prostate cancer. While a large number of lncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. In this review, we highlight recent findings on the functional role and molecular mechanisms of lncRNAs in the progression of prostate cancer and evaluate their use as potential biomarkers and therapeutic targets.

  17. Integration of Prostate Cancer Clinical Data Using an Ontology

    PubMed Central

    Min, Hua; Manion, Frank J.; Goralczyk, Elizabeth; Wong, Yu-Ning; Ross, Eric; Beck, J. Robert

    2009-01-01

    It is increasingly important for investigators to efficiently and effectively access, interpret, and analyze the data from diverse biological, literature, and annotation sources in a unified way. The heterogeneity of biomedical data and the lack of metadata are the primary sources of the difficulty for integration, presenting major challenges to effective search and retrieval of the information. As a proof of concept, the Prostate Cancer Ontology (PCO) is created for the development of the Prostate Cancer Information System (PCIS). PCIS is applied to demonstrate how the ontology is utilized to solve the semantic heterogeneity problem from the integration of two prostate cancer related database systems at the Fox Chase Cancer Center. As the results of the integration process, the semantic query language SPARQL is applied to perform the integrated queries across the two database systems based on PCO. PMID:19497389

  18. Integration of prostate cancer clinical data using an ontology.

    PubMed

    Min, Hua; Manion, Frank J; Goralczyk, Elizabeth; Wong, Yu-Ning; Ross, Eric; Beck, J Robert

    2009-12-01

    It is increasingly important for investigators to efficiently and effectively access, interpret, and analyze the data from diverse biological, literature, and annotation sources in a unified way. The heterogeneity of biomedical data and the lack of metadata are the primary sources of the difficulty for integration, presenting major challenges to effective search and retrieval of the information. As a proof of concept, the Prostate Cancer Ontology (PCO) is created for the development of the Prostate Cancer Information System (PCIS). PCIS is applied to demonstrate how the ontology is utilized to solve the semantic heterogeneity problem from the integration of two prostate cancer related database systems at the Fox Chase Cancer Center. As the results of the integration process, the semantic query language SPARQL is applied to perform the integrated queries across the two database systems based on PCO.

  19. Cleveland Clinic experience with interstitial laser coagulation of the prostate

    NASA Astrophysics Data System (ADS)

    Ulchaker, James C.; Ng, Christopher S.; Palone, David; Angie, Michelle; Kursh, Elroy D.

    2000-05-01

    Transurethral resection of the prostate (TURP) has long been considered the gold standard therapy for benign prostatic hyperplasia (BPH). The problems associated with the TURP, which have been extensively described, include significant bleeding, TUR syndrome, incontinence, stricture, bladder neck contracture, and sexual dysfunction. The desire for simpler, less morbid alternative therapies to TURP has led to an eruption of research and development in the last decade. This is fueled by the continued research for more economical alternatives in our current high cost health care system.

  20. Monte Carlo study of interseed attenuation and tissue composition effect for clinical cases of prostate permanent implants.

    NASA Astrophysics Data System (ADS)

    Carrier, Jean-Francois; Beaulieu, Luc

    2006-03-01

    Monte Carlo simulations were used to study the interseed attenuation and the effect of tissue composition on prostate implant dosimetry. Using computed tomography images of postimplant analysis, the precise anatomy of the patient was considered voxel by voxel. The physical density of each voxel was set according to the Hounsfield Unit and the specific elemental composition of each voxel was set depending on the radiation-oncologist organ contours and the local density. Mixes of different tissues were available: muscle, prostate tissue, rectum tissue, adipose tissue, bone and prostate calcification. Typically, more than 300 combinations of elemental composition and density were used for each patient. The Monte Carlo dosimetry results were compared to the clinically approved TG43-based calculations for 30 patients. The results show an interseed attenuation of about 4.5% for the D90 parameter (minimal dose received by 90% of the target volume). The effect of the tissue composition varies from one patient to the other. Globally, the difference between the TG43-based calculations and the Monte Carlo results can reach more than 10 Gy for the D90 values. From a clinical perspective, the difference level can be non-negligible for the target volume and for the surrounding organs at risk.

  1. Cysteine (C)-X-C Receptor 4 Undergoes Transportin 1-Dependent Nuclear Localization and Remains Functional at the Nucleus of Metastatic Prostate Cancer Cells

    PubMed Central

    Don-Salu-Hewage, Ayesha S.; Chan, Siu Yuen; McAndrews, Kathleen M.; Chetram, Mahandranauth A.; Dawson, Michelle R.; Bethea, Danaya A.; Hinton, Cimona V.

    2013-01-01

    The G-protein coupled receptor (GPCR), Cysteine (C)-X-C Receptor 4 (CXCR4), plays an important role in prostate cancer metastasis. CXCR4 is generally regarded as a plasma membrane receptor where it transmits signals that support transformation, progression and eventual metastasis. Due to the central role of CXCR4 in tumorigenesis, therapeutics approaches such as antagonist and monoclonal antibodies have focused on receptors that exist on the plasma membrane. An emerging concept for G-protein coupled receptors is that they may localize to and associate with the nucleus where they retain function and mediate nuclear signaling. Herein, we demonstrate that CXCR4 associated with the nucleus of malignant prostate cancer tissues. Likewise, expression of CXCR4 was detected in nuclear fractions among several prostate cancer cell lines, compared to normal prostate epithelial cells. Our studies identified a nuclear pool of CXCR4 and we defined a nuclear transport pathway for CXCR4. We reveal a putative nuclear localization sequence (NLS), ‘RPRK’, within CXCR4 that contributed to nuclear localization. Additionally, nuclear CXCR4 interacted with Transportinβ1 and Transportinβ1-binding to CXCR4 promoted its nuclear translocation. Importantly, Gαi immunoprecipitation and calcium mobilization studies indicated that nuclear CXCR4 was functional and participated in G-protein signaling, revealing that the nuclear pool of CXCR4 retained function. Given the suggestion that functional, nuclear CXCR4 may be a mechanism underlying prostate cancer recurrence, increased metastatic ability and poorer prognosis after tumors have been treated with therapy that targets plasma membrane CXCR4, these studies addresses a novel mechanism of nuclear signaling for CXCR4, a novel mechanism of clinical targeting, and demonstrate an active nuclear pool that provides important new information to illuminate what has been primarily clinical reports of nuclear CXCR4. PMID:23468933

  2. Clinical, pathological and molecular prognostic factors in prostate cancer decision-making process.

    PubMed

    Pugliese, Dario; Palermo, Giuseppe; Totaro, Angelo; Bassi, Pier Francesco; Pinto, Francesco

    2016-01-01

    Prostate cancer is the most common urologic neoplasm and the second leading cause of cancer-related death among men in many developed countries. Given the highly heterogeneous behaviour of the disease, there is a great need for prognostic factors, in order to stratify the clinical risk and give the best treatment options to the patient. Clinical factors, such as prostate-specific antigen value and derivatives, and pathological factors, such as stage and Gleason grading, are well kown prognostic factors. Nomograms can provide useful prediction in each clinical sceario. The field of molecular biomarkers is briskly evolving towards personalized medicine. TMPRSS2-ERG fusion, deletion of PTEN ed and gene panels are some of the more extensively explored molecular features in prostate cancer outcome prediction. In the near future, circulating tumour cells, exosomes and microRNAs could give us further, not invasive important tools.

  3. Optimization of Radiation Therapy Techniques for Prostate Cancer With Prostate-Rectum Spacers: A Systematic Review

    SciTech Connect

    Mok, Gary; Benz, Eileen; Vallee, Jean-Paul; Miralbell, Raymond; Zilli, Thomas

    2014-10-01

    Dose-escalated radiation therapy for localized prostate cancer improves disease control but is also associated with worse rectal toxicity. A spacer placed between the prostate and rectum can be used to displace the anterior rectal wall outside of the high-dose radiation regions and potentially minimize radiation-induced rectal toxicity. This systematic review focuses on the published data regarding the different types of commercially available prostate-rectum spacers. Dosimetric results and preliminary clinical data using prostate-rectum spacers in patients with localized prostate cancer treated by curative radiation therapy are compared and discussed.

  4. Radical perineal prostatectomy: a model for evaluating local response of prostate therapy.

    PubMed

    Paulson, David F; Vieweg, Johannes W G

    2002-08-01

    To establish a model for preoperative counseling and postoperative outcome in patients who choose radical perineal prostatectomy for the clinically localized prostatic malignancy, the following postulates have been identified: (1) the use of preoperative prostate specific antigen (PSA) and Gleason Sum at the time of biopsy can be used to segregate the outcome among patients with Gleason Sum 2 through 6, 7, and 8 through 10. (2) Postoperative PSA levels are excellent surrogate endpoints for defining disease control. (3) The biology of the primary malignancy defines the interval of death after recurrence. A total of 1242 men with the median age of 65.2 years who had Stage cT 1-2 NOMO disease underwent radical perineal prostatectomy. The final pathologic specimen was characterized with regard to disease extent and Gleason Sum. Patients were followed at 2 weeks, 2 months, and then at 6-month intervals for biochemical, physical, and radiographic evidence of disease recurrence. Outcome was evaluated by determining time to biochemical failure (PSA 0.5 ng/ml or greater) or cancer associated death (death with a detectable PSA independent of treatment). Median time to non-cancer death was 19.3 years. Median cancer-associated death endpoints were not reached by patients with organ confined disease. Results were 17.7 years for specimen confined disease and 12.7 years for margin positive disease. At 5 years, 8, 35, and 65% of patients with organ confined, specimen confined, or margin positive disease, respectively, had PSA failure. This served as an excellent surrogate endpoint, preceding cancer associated death by 5-12 years, depending on the biological aggressiveness predicted by Gleason Sum. When segregated by Gleason Sum 2 through 6, 7 or 8 through 10 at the time of biopsy, there was a distinct differentiation in survival among these Gleason Sum classifications according to the PSA at the time of biopsy. This study confirms our postulates and provides guidelines for

  5. Long-term cancer-related fatigue outcomes in patients with locally advanced prostate cancer after intensity-modulated radiotherapy combined with hormonal therapy

    PubMed Central

    Luo, Hua-Chun; Lei, Yong; Cheng, Hui-Hua; Fu, Zhi-Chao; Liao, Shao-Guang; Feng, Jing; Yin, Qin; Chen, Qun-Hua; Lin, Gui-Shan; Zhu, Jin-Feng; Xu, Jian-Feng; Wang, Dian

    2016-01-01

    Abstract The aim of our study was to investigate the relationship between cancer-related fatigue and clinical parameters, and the effect factors of fatigue for the prostate cancer patients. Long-term follow-up is performed using the Fatigue Symptom Inventory before treatment (A), at the end of intensity-modulated radiotherapy (B), and 3 months (C), 12 months (D), 24 months (E), 36 months (F), and 48 months (G) after the end of intensity-modulated radiotherapy. Three dimensions of fatigue are assessed during follow-up: severity, perceived interference with quality of life, and duration in the past week. In all, 97 patients with locally advanced prostate cancer were enrolled in the study. Median follow-up time was 43.9 months. The fatigue index was significantly higher in the prostate-specific antigen >20 ng/mL, Gleason score >8, the Eastern Cooperative Oncology Group scores, and the higher education. The most severe fatigue occurred at time points B and C. The score for duration of fatigue fluctuated across the time points, with significantly increased scores at time points D, E, and F. In conclusion, we show that cancer-related fatigue is the important symptom which affects the quality of life for the prostate cancer patients. For patients with locally advanced prostate cancer with a high Eastern Cooperative Oncology Group score, a Gleason score of >8 points, prostate-specific antigen levels of >20 ng/mL, and high education, attention should be paid to the interference of fatigue with quality of life, especially general level of activity, ability to concentrate, and mood, after radiotherapy combined with hormonal therapy. PMID:27336890

  6. Survey of Clinical and Pathological Characteristics and Outcomes of Patients With Prostate Cancer

    PubMed Central

    Alizadeh, M.; Alizadeh, S.

    2014-01-01

    Introduction: The importance of implementation: Prostate cancer is the most common malignancy in men and the second leading cause of cancer death in developed countries. Therefore, further studies about the protests of disease, diagnosis and timely treatment are essential. Study Method: In this study, 80 prostate cancer patients admitted to Imam Khomeini Hospital, Urmia in Iran from 2000 to 2008 were reviewed. Patients were studied according to their age, clinical protests, Gleason scoring, positive family history, smoking, type of treatment and post-treatment conditions. Questionnaires were adjusted based on the objectives and the data were extracted from the medical records of patients and the desired results were achieved. Results: In this study, the most common age group for prostate cancer is older than 60 years (92/5%). The most common type of pathology for prostate cancer is adenocarcinoma that 93.75% of cases are included. Secondary TCC with secondary source is present in 5% and sarcoma in 1.25% of cases. 46.25% of patients with prostate cancer are smokers. The most common clinical symptoms among patients are obstructive symptoms (56.25%), and irritation of the urinary tract (52.81%). Hematuria in 26.25% and urinary incontinence in 5% of cases have been recorded. 16.3% of patients referred with metastatic symptoms. Most patients with prostate cancer have Gleason score 5-7 (40%). All patients were undergoing prostatectomy (82.5% TURP and 17.5% SPP) and 47.5% of cases were bilateral orchiectomy. The cases reviewed, 22 were followed that included 27.5% of cases. Among them, 6 people have died due prostate cancer (27.27%) that the mean age of the patients after diagnosis until death was 34.4 months. 2 others died from other causes (9.09%). The remaining 14 cases were elder patients with a mean follow-up duration of 44 months. Conclusion: According to the results obtained in the present study, the most common type of prostate cancer pathology is adenocarcinoma

  7. Salvage local therapy for radiation-recurrent prostate cancer – where are we?

    PubMed Central

    Zdrojowy, Romuald; Dembowski, Janusz; Małkiewicz, Bartosz; Tupikowski, Krzysztof

    2016-01-01

    Introduction Prostate cancer is the most frequent cancer among males in Europe and a leading cause of cancer deaths, with similar proportion in other developed countries. For more than twenty years, external-beam radiation therapy, alongside with radical prostatectomy, has been used as a primary radical therapeutic approach for localized prostate cancer. Yet, EBRT failures relate to 22–69% following curative radiotherapy (± androgen deprivation therapy). Additionally, a proportion of these men will have a biopsy-proven local recurrence. Material and methods The Medline and Web of Science databases were searched without a time limit during March 2016 using the terms ‘prostate cancer’ in conjunction with ‘radiotherapy’, ‘recurrence’, ‘biochemical’, ‘salvage’, ‘brachytherapy’, ‘prostatectomy’, ‘HIFU’, ‘cryotherapy’ and ‘focal’. The search was limited to the English, Polish, German and Spanish literature. Results Currently, salvage treatment after failed radiotherapy includes radical prostatectomy, brachytherapy and ablative whole-gland therapies, such as cryotherapy and high intensity focused ultrasound. New approaches, so called focal salvage therapy, involve ablation of only the zone of recurrence in order to decrease tissue injury and therefore to diminish morbidity. Conclusions At present no authoritative recommendations can be concluded because of the absence of randomized data with standardized definitions and protocols. Nevertheless, we believe that local salvage treatment should be at least considered in patients after biochemical relapse following radiotherapy. PMID:27729992

  8. Localization of MCT2 at peroxisomes is associated with malignant transformation in prostate cancer

    PubMed Central

    Valença, Isabel; Pértega-Gomes, Nelma; Vizcaino, José Rámon; Henrique, Rui M; Lopes, Carlos; Baltazar, Fátima; Ribeiro, Daniela

    2015-01-01

    Previous studies on monocarboxylate transporters expression in prostate cancer (PCa) have shown that monocarboxylate transporter 2 (MCT2) was clearly overexpressed in prostate malignant glands, pointing it out as a putative biomarker for PCa. However, its localization and possible role in PCa cells remained unclear. In this study, we demonstrate that MCT2 localizes mainly at peroxisomes in PCa cells and is able to take advantage of the peroxisomal transport machinery by interacting with Pex19. We have also shown an increase in MCT2 expression from non-malignant to malignant cells that was directly correlated with its peroxisomal localization. Upon analysis of the expression of several peroxisomal β-oxidation proteins in PIN lesions and PCa cells from a large variety of human prostate samples, we suggest that MCT2 presence at peroxisomes is related to an increase in β -oxidation levels which may be crucial for malignant transformation. Our results present novel evidence that may not only contribute to the study of PCa development mechanisms but also pinpoint novel targets for cancer therapy. PMID:25639644

  9. Calculated organ doses using Monte Carlo simulations in a reference male phantom undergoing HDR brachytherapy applied to localized prostate carcinoma

    SciTech Connect

    Candela-Juan, Cristian; Perez-Calatayud, Jose; Ballester, Facundo; Rivard, Mark J.

    2013-03-15

    Purpose: The aim of this study was to obtain equivalent doses in radiosensitive organs (aside from the bladder and rectum) when applying high-dose-rate (HDR) brachytherapy to a localized prostate carcinoma using {sup 60}Co or {sup 192}Ir sources. These data are compared with results in a water phantom and with expected values in an infinite water medium. A comparison with reported values from proton therapy and intensity-modulated radiation therapy (IMRT) is also provided. Methods: Monte Carlo simulations in Geant4 were performed using a voxelized phantom described in International Commission on Radiological Protection (ICRP) Publication 110, which reproduces masses and shapes from an adult reference man defined in ICRP Publication 89. Point sources of {sup 60}Co or {sup 192}Ir with photon energy spectra corresponding to those exiting their capsules were placed in the center of the prostate, and equivalent doses per clinical absorbed dose in this target organ were obtained in several radiosensitive organs. Values were corrected to account for clinical circumstances with the source located at various positions with differing dwell times throughout the prostate. This was repeated for a homogeneous water phantom. Results: For the nearest organs considered (bladder, rectum, testes, small intestine, and colon), equivalent doses given by {sup 60}Co source were smaller (8%-19%) than from {sup 192}Ir. However, as the distance increases, the more penetrating gamma rays produced by {sup 60}Co deliver higher organ equivalent doses. The overall result is that effective dose per clinical absorbed dose from a {sup 60}Co source (11.1 mSv/Gy) is lower than from a {sup 192}Ir source (13.2 mSv/Gy). On the other hand, equivalent doses were the same in the tissue and the homogeneous water phantom for those soft tissues closer to the prostate than about 30 cm. As the distance increased, the differences of photoelectric effect in water and soft tissue, and appearance of other materials

  10. External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

    SciTech Connect

    Cho, Eunpi; Mostaghel, Elahe A.; Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A.; Kurland, Brenda F.; Marck, Brett T.; Matsumoto, Alvin M.; Dalkin, Bruce L.; Montgomery, R. Bruce

    2015-06-01

    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 the 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

  11. NMR-based metabolomics of prostate cancer: a protagonist in clinical diagnostics.

    PubMed

    Kumar, Deepak; Gupta, Ashish; Nath, Kavindra

    2016-06-01

    Advances in the application of NMR spectroscopy-based metabolomic profiling of prostate cancer comprises a potential tactic for understanding the impaired biochemical pathways arising due to a disease evolvement and progression. This technique involves qualitative and quantitative estimation of plethora of small molecular weight metabolites of body fluids or tissues using state-of-the-art chemometric methods delivering an important platform for translational research from basic to clinical, to reveal the pathophysiological snapshot in a single step. This review summarizes the present arrays and recent advancements in NMR-based metabolomics and a glimpse of currently used medical imaging tactics, with their role in clinical diagnosis of prostate cancer. PMID:26959614

  12. Feasibility of vibro-acoustography with a quasi-2D ultrasound array transducer for detection and localizing of permanent prostate brachytherapy seeds: A pilot ex vivo study

    SciTech Connect

    Mehrmohammadi, Mohammad; Kinnick, Randall R.; Fatemi, Mostafa; Alizad, Azra; Davis, Brian J.

    2014-09-15

    Purpose: Effective permanent prostate brachytherapy (PPB) requires precise placement of radioactive seeds in and around the prostate. The impetus for this research is to examine a new ultrasound-based imaging modality, vibro-acoustography (VA), which may serve to provide a high rate of PPB seed detection while also effecting enhanced prostate imaging. The authors investigate the ability of VA, implemented on a clinical ultrasound (US) scanner and equipped with a quasi-2D (Q2D) array US transducer, to detect and localize PPB seeds in excised prostate specimens. Methods: Nonradioactive brachytherapy seeds were implanted into four excised cadaver prostates. A clinical US scanner equipped with a Q2D array US transducer was customized to acquire both US and C-scan VA images at various depths. The VA images were then used to detect and localize the implanted seeds in prostate tissue. To validate the VA results, computed tomography (CT) images of the same tissue samples were obtained to serve as the reference by which to evaluate the performance of VA in PPB seed detection. Results: The results indicate that VA is capable of accurately identifying the presence and distribution of PPB seeds with a high imaging contrast. Moreover, a large ratio of the PPB seeds implanted into prostate tissue samples could be detected through acquired VA images. Using CT-based seed identification as the standard, VA was capable of detecting 74%–92% of the implanted seeds. Additionally, the angular independency of VA in detecting PPB seeds was demonstrated through a well-controlled phantom experiment. Conclusions: Q2DVA detected a substantial portion of the seeds by using a 2D array US transducer in excised prostate tissue specimens. While VA has inherent advantages associated with conventional US imaging, it has the additional advantage of permitting detection of PPB seeds independent of their orientation. These results suggest the potential of VA as a method for PPB imaging that

  13. CIP2A is a candidate therapeutic target in clinically challenging prostate cancer cell populations

    PubMed Central

    Khanna, Anchit; Rane, Jayant K.; Kivinummi, Kati K.; Urbanucci, Alfonso; Helenius, Merja A.; Tolonen, Teemu T.; Saramäki, Outi R.; Latonen, Leena; Manni, Visa; Pimanda, John E.; Maitland, Norman J.; Westermarck, Jukka; Visakorpi, Tapio

    2015-01-01

    Residual androgen receptor (AR)-signaling and presence of cancer stem-like cells (SCs) are the two emerging paradigms for clinically challenging castration-resistant prostate cancer (CRPC). Therefore, identification of AR-target proteins that are also overexpressed in the cancer SC population would be an attractive therapeutic approach. Our analysis of over three hundred clinical samples and patient-derived prostate epithelial cultures (PPECs), revealed Cancerous inhibitor of protein phosphatase 2A (CIP2A) as one such target. CIP2A is significantly overexpressed in both hormone-naïve prostate cancer (HN-PC) and CRPC patients. CIP2A is also overexpressed, by 3- and 30-fold, in HN-PC and CRPC SCs respectively. In vivo binding of the AR to the intronic region of CIP2A and its functionality in the AR-moderate and AR-high expressing LNCaP cell-model systems is also demonstrated. Further, we show that AR positively regulates CIP2A expression, both at the mRNA and protein level. Finally, CIP2A depletion reduced cell viability and colony forming efficiency of AR-independent PPECs as well as AR-responsive LNCaP cells, in which anchorage-independent growth is also impaired. These findings identify CIP2A as a common denominator for AR-signaling and cancer SC functionality, highlighting its potential therapeutic significance in the most clinically challenging prostate pathology: castration-resistant prostate cancer. PMID:25965834

  14. Metabolomics and its Application to the Development of Clinical Laboratory Tests for Prostate Cancer

    PubMed Central

    McDunn, Jonathan E.; Stirdivant, Steven M.; Ford, Lisa A.

    2015-01-01

    Introduction There is a critical need to develop clinical laboratory assays that provide risk assessment for men at elevated risk for prostate cancer, and once diagnosed, could further identify those men with clinically significant disease. Methods Recent advancements in analytical instrumentation have enabled mass spectrometry-based metabolomics methodologies. Further advancements in chromatographic techniques have facilitated high throughput, quantitative assays for a broad spectrum of biochemicals. Results Screening metabolomics techniques have been applied to biospecimens from large cohorts of men comparing those individuals with prostate cancer to those with no evidence of malignancy. Work beginning in tissues has identified biochemical profiles that correlate with disease and disease severity, including tumor grade and stage. Some of these metabolic abnormalities, such as dramatic elevations in sarcosine, have been found to translate into biological fluids, especially blood and urine, which can be sampled in a minimally invasive manner. Discussion The differential abundances of these tumor-associated metabolites have been found to improve the performance of clinical prognostic/diagnostic tools. Conclusion The outlook is bright for metabolomic technology to address clinical diagnostic needs for prostate cancer patient management. Early validation of specific clinical tests provides a preview of further successes in this area. Metabolomics has shown its utility to complement and augment traditional clinical approaches as well as emerging genomic, transcriptomic and proteomic methodologies, and is expected to play a key role in the precision medicine-based management of the prostate cancer patient.

  15. MOLECULAR IMAGING OF PROSTATE CANCER: translating molecular biology approaches into the clinical realm

    PubMed Central

    Vargas, Hebert Alberto; Grimm, Jan; Donati, Olivio F.; Sala, Evis; Hricak, Hedvig

    2016-01-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980’s. Most prostate cancers today are detected at early stages of the disease and are considered “indolent”, however some patients’ prostate cancers demonstrate a more aggressive behavior which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterizes this disease has lead to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumor detection alone to distinguishing patients with indolent tumors that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumors that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualization of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. PMID:25693661

  16. A comparison of CT- and ultrasound-based imaging to localize the prostate for external beam radiotherapy

    SciTech Connect

    McNair, Helen A. . E-mail: Helen.McNair@rmh.nhs.uk; Mangar, Stephen A.; Coffey, Jerome; Shoulders, Beverley; Hansen, Vibeke N.; Norman, Andrew; Staffurth, John; Sohaib, S. Aslam; Warrington, Alan P.; Dearnaley, David P.

    2006-07-01

    Purpose: This study assesses the accuracy of NOMOS B-mode acquisition and targeting system (BAT) compared with computed tomography (CT) in localizing the prostate. Methods and Materials: Twenty-six patients were CT scanned, and the prostate was localized by 3 observers using the BAT system. The BAT couch shift measurements were compared with the CT localization. Six of the patients had gold markers present in the prostate, and the prostate movement determined by BAT was compared with the movement determined by the gold markers. Results: Using the BAT system, the 3 observers determined the prostate position to be a mean of 1-5 mm over all directions with respect to the CT. The proportion of readings with a difference >3 mm between the observers was in the range of 25% to 44%. The prostate movement based on gold markers was an average of 3-5 mm different from that measured by BAT. The literature assessing the accuracy and reproducibility on BAT is summarized and compared with our findings. Conclusions: We have found that there are systematic differences between the BAT-defined prostate position compared with that estimated on CT using gold grain marker seeds.

  17. Eosinophilic prostatitis and prostatic specific antigen.

    PubMed

    Liu, S; Miller, P D; Holmes, S A; Christmas, T J; Kirby, R S

    1992-01-01

    Eosinophilic prostatitis is a rare form of abacterial prostatitis with uncertain aetiology. Its clinical presentation, like other types of abacterial prostatitis, commonly mimics carcinoma of the prostate. Transrectal ultrasound may be helpful in the diagnosis of prostatitis but histological confirmation is necessary. Prostatic specific antigen has been widely used in the diagnosis and follow-up of patients with prostatic carcinoma. High levels of this antigen (greater than 30 micrograms/l) have been claimed to be highly specific for prostate cancer, although lesser elevations may also occur in patients with large benign prostate glands and in bacterial prostatitis. We report 3 patients with histologically proven eosinophilic prostatitis and high levels of prostatic specific antigen. This diagnosis may closely mimic carcinoma of the prostate and must be excluded by histological examination of biopsy material before treatment for presumed prostate carcinoma is initiated.

  18. Automatic localization of the prostate for on-line or off-line image-guided radiotherapy

    SciTech Connect

    Smitsmans, Monique H.P.; Wolthaus, Jochem W.H.; Artignan, Xavier; Bois, Josien de; Jaffray, David A.; Lebesque, Joos V.; Herk, Marcel van . E-mail: portal@nki.nl

    2004-10-01

    Purpose: With higher radiation dose, higher cure rates have been reported in prostate cancer patients. The extra margin needed to account for prostate motion, however, limits the level of dose escalation, because of the presence of surrounding organs at risk. Knowledge of the precise position of the prostate would allow significant reduction of the treatment field. Better localization of the prostate at the time of treatment is therefore needed, e.g. using a cone-beam computed tomography (CT) system integrated with the linear accelerator. Localization of the prostate relies upon manual delineation of contours in successive axial CT slices or interactive alignment and is fairly time-consuming. A faster method is required for on-line or off-line image-guided radiotherapy, because of prostate motion, for patient throughput and efficiency. Therefore, we developed an automatic method to localize the prostate, based on 3D gray value registration. Methods and materials: A study was performed on conventional repeat CT scans of 19 prostate cancer patients to develop the methodology to localize the prostate. For each patient, 8-13 repeat CT scans were made during the course of treatment. First, the planning CT scan and the repeat CT scan were registered onto the rigid bony structures. Then, the delineated prostate in the planning CT scan was enlarged by an optimum margin of 5 mm to define a region of interest in the planning CT scan that contained enough gray value information for registration. Subsequently, this region was automatically registered to a repeat CT scan using 3D gray value registration to localize the prostate. The performance of automatic prostate localization was compared to prostate localization using contours. Therefore, a reference set was generated by registering the delineated contours of the prostates in all scans of all patients. Gray value registrations that showed large differences with respect to contour registrations were detected with a {chi

  19. Clinical and economic considerations in the treatment of prostate cancer.

    PubMed

    Varenhorst, E; Carlsson, P; Pedersen, K

    1994-08-01

    Prostate cancer is a growing health problem with considerable economic consequences. Despite progress in the management of this disease, few areas in medicine generate greater disagreement. The larger part of healthcare resources are allocated to 'halfway technologies' aimed at palliative intervention to prolong life, while a relatively small part goes to measures aimed at preventing or curing the disease. The aetiology of this cancer is multifactorial and no practical measures for primary prevention are known. The number of patients diagnosed with prostate cancer is increasing steadily. The age-adjusted mortality, however, has increased only slightly. In its early stages, prostate cancer is often asymptomatic and is usually not diagnosed until it has advanced. Programmes for the early detection of prostate cancer (screening) claimed to reduce morbidity and mortality are a matter of controversy. Furthermore, there has been much debate regarding optimal treatment in the early stages of the disease. Economic considerations have not as yet been integrated into studies concerning localised prostate cancer. The routine first-line treatment of advanced prostate cancer usually involves some type of endocrine treatment. The most straightforward technique is surgical castration. Oral estrogens are as effective as castration, but have significant cardiovascular adverse effects. These may possibly be prevented if estrogens are given parenterally. A third principal endocrine treatment is the administration of antiandrogens. Medical castration can be attained by the administration of recently developed synthetic peptides, gonadotrophin-releasing hormone {luteinising hormone-releasing hormone (LHRH)} (GnRH) analogue agonists which are given parenterally. The advantage of this type of medical castration is that the trauma of surgical castration and the adverse effects of oral estrogens are avoided. In an attempt to improve the results obtained with endocrine treatment, the

  20. Minimally Invasive Ablative Therapies for Definitive Treatment of Localized Prostate Cancer in the Primary Setting

    PubMed Central

    Lee, Eugene W.; Huang, William C.

    2011-01-01

    Traditionally, the patient with a new diagnosis of localized prostate cancer faces either radical therapy, in the form of surgery or radiation, or active surveillance. A growing subset of these men may not be willing to accept the psychological burden of active surveillance nor the side effects of extirpative or radiation therapy. Local ablative therapies including cryotherapy, high-intensity focused ultrasound, and vascular-targeted photodynamic therapy have emerged as a means for minimally invasive definitive treatment. These treatments are well tolerated with decreased morbidity in association with improvements in technology; however, long-term oncologic efficacy remains to be determined. PMID:22110985

  1. Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer: A Prognostic Modelling Study

    PubMed Central

    Wright, Karen A.; Muir, Kenneth R.; Gavin, Anna

    2016-01-01

    Introduction Over 80% of the nearly 1 million men diagnosed with prostate cancer annually worldwide present with localised or locally advanced non-metastatic disease. Risk stratification is the cornerstone for clinical decision making and treatment selection for these men. The most widely applied stratification systems use presenting prostate-specific antigen (PSA) concentration, biopsy Gleason grade, and clinical stage to classify patients as low, intermediate, or high risk. There is, however, significant heterogeneity in outcomes within these standard groupings. The International Society of Urological Pathology (ISUP) has recently adopted a prognosis-based pathological classification that has yet to be included within a risk stratification system. Here we developed and tested a new stratification system based on the number of individual risk factors and incorporating the new ISUP prognostic score. Methods and Findings Diagnostic clinicopathological data from 10,139 men with non-metastatic prostate cancer were available for this study from the Public Health England National Cancer Registration Service Eastern Office. This cohort was divided into a training set (n = 6,026; 1,557 total deaths, with 462 from prostate cancer) and a testing set (n = 4,113; 1,053 total deaths, with 327 from prostate cancer). The median follow-up was 6.9 y, and the primary outcome measure was prostate-cancer-specific mortality (PCSM). An external validation cohort (n = 1,706) was also used. Patients were first categorised as low, intermediate, or high risk using the current three-stratum stratification system endorsed by the National Institute for Health and Care Excellence (NICE) guidelines. The variables used to define the groups (PSA concentration, Gleason grading, and clinical stage) were then used to sub-stratify within each risk category by testing the individual and then combined number of risk factors. In addition, we incorporated the new ISUP prognostic score as a discriminator

  2. Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer: A Prognostic Modelling Study

    PubMed Central

    Wright, Karen A.; Muir, Kenneth R.; Gavin, Anna

    2016-01-01

    Introduction Over 80% of the nearly 1 million men diagnosed with prostate cancer annually worldwide present with localised or locally advanced non-metastatic disease. Risk stratification is the cornerstone for clinical decision making and treatment selection for these men. The most widely applied stratification systems use presenting prostate-specific antigen (PSA) concentration, biopsy Gleason grade, and clinical stage to classify patients as low, intermediate, or high risk. There is, however, significant heterogeneity in outcomes within these standard groupings. The International Society of Urological Pathology (ISUP) has recently adopted a prognosis-based pathological classification that has yet to be included within a risk stratification system. Here we developed and tested a new stratification system based on the number of individual risk factors and incorporating the new ISUP prognostic score. Methods and Findings Diagnostic clinicopathological data from 10,139 men with non-metastatic prostate cancer were available for this study from the Public Health England National Cancer Registration Service Eastern Office. This cohort was divided into a training set (n = 6,026; 1,557 total deaths, with 462 from prostate cancer) and a testing set (n = 4,113; 1,053 total deaths, with 327 from prostate cancer). The median follow-up was 6.9 y, and the primary outcome measure was prostate-cancer-specific mortality (PCSM). An external validation cohort (n = 1,706) was also used. Patients were first categorised as low, intermediate, or high risk using the current three-stratum stratification system endorsed by the National Institute for Health and Care Excellence (NICE) guidelines. The variables used to define the groups (PSA concentration, Gleason grading, and clinical stage) were then used to sub-stratify within each risk category by testing the individual and then combined number of risk factors. In addition, we incorporated the new ISUP prognostic score as a discriminator

  3. Assessing the Role of Volumetric Modulated Arc Therapy (VMAT) Relative to IMRT and Helical Tomotherapy in the Management of Localized, Locally Advanced, and Post-Operative Prostate Cancer

    SciTech Connect

    Davidson, Melanie T.M.; Blake, Samuel J.; Batchelar, Deidre L.; Cheung, Patrick; Mah, Katherine

    2011-08-01

    Purpose: To quantify differences in treatment delivery efficiency and dosimetry between step-and-shoot intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT) for prostate treatment. Methods and Materials: Twenty-five prostate cancer patients were selected retrospectively for this planning study. Treatment plans were generated for: prostate alone (n = 5), prostate + seminal vesicles (n = 5), prostate + seminal vesicles + pelvic lymph nodes (n = 5), prostate bed (n = 5), and prostate bed + pelvic lymph nodes (n = 5). Target coverage, dose homogeneity, integral dose, monitor units (MU), and sparing of organs at risk (OAR) were compared across techniques. Time required to deliver each plan was measured. Results: The dosimetric quality of IMRT, VMAT, and HT plans were comparable for target coverage (planning target volume V95%, clinical target volume V100% all >98.7%) and sparing of organs at risk (OAR) for all treatment groups. Although HT resulted in a slightly higher integral dose and mean doses to the OAR, it yielded a lower maximum dose to all OAR examined. VMAT resulted in reductions in treatment times over IMRT (mean = 75%) and HT (mean = 70%). VMAT required 15-38% fewer monitor units than IMRT over all treatment volumes, with the reduction per fraction ranging from 100-423 MU from the smallest to largest volumes. Conclusions: VMAT improves efficiency of delivery for equivalent dosimetric quality as IMRT and HT across various prostate cancer treatment volumes in the intact and postoperative settings.

  4. Elevated expression of HIF-lα in actively growing prostate tissues is associated with clinical features of benign prostatic hyperplasia

    PubMed Central

    Li, Xin; Wang, Hui; Liu, Shuai; Wu, Haihu; Bi, Dongbin; Ding, Kejia; Lu, Jiaju

    2016-01-01

    Background Benign prostatic hyperplasia (BPH) is one of the most common diseases in middle-age or older men. Increasing evidence has shown that BPH is associated with hypoxia microenvironment. Methods We retrospectively collected patient data and tissue samples from fetal prostates(FP), normal prostates(NP), intra-acinar of BPH, peri-acinar of BPH, prostate cancers and sarcomas of prostate. The expression of HIF-1α, as well as VEGF was visualized by immunohistochemistry and statistically analyzed with clinical parameters. Results Expression of HIF-lα was observed in intra-acinar of BPH (69.5%), prostate cancer (85.7%) and all FPs, while NP and peri-acinar of BPH tissues were all stained negative. HIF-lα levels in FPs and the malignant tumors were higher than BPH tissues(p < 0.05), and the expression of HIF-lα in intra-acinar of BPH was higher than NP and peri-acinar of BPH (p < 0.05). The expression of HIF-lα was correlated with the weight of intra-acinar of prostate (p < 0.05). And patients with prostate weight larger that 72.45g were prone to have HIF-lα moderate-positive expression, according to the ROC curve (AUC = 0.734, 95%CI = 0.630-0.838). Moreover, the risk of acute urine retention (AUR) for HIF-lα moderate-positive patients increased significantly (OR=5.517, 95%CI = 2.434-12.504). Conclusions HIF-lα expression is increased in highly proliferative prostate tissues and correlated with the weight of intra-acinar prostate. Moreover, HIF-lα is also an independent risk factor for AUR occurrence in BPH patients. PMID:26919249

  5. Impact of Image Guidance on Outcomes After External Beam Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Kupelian, Patrick A. Willoughby, Twyla R.; Reddy, Chandana A.; Klein, Eric A.; Mahadevan, Arul

    2008-03-15

    Purpose: To verify whether rectal distention at the time of planning impacts outcomes in patients with localized prostate cancer treated with daily image guidance. Methods and Materials: Between 1998 and 2002, a total of 488 prostate cancer patients were treated with intensity-modulated radiotherapy. The radiation dose was 70 Gy delivered at 2.5 Gy per fraction in all cases. All cases were treated with a 4-mm margin posteriorly. In all cases the total rectal volume documented on the CT scan was used for treatment planning. No special bowel preparation instructions were given, either for the simulation or the daily treatments. Before each daily treatment, alignment of the prostate was performed with the B-mode acquisition and targeting (BAT) transabdominal ultrasound system. The median follow-up for all 488 patients was 60 months (range, 24-96 months). Results: For all patients the biochemical relapse-free survival (bRFS) rate at 5 years was 86%. The 5-year bRFS rate for the rectal distention <50 cm{sup 3}, 50 to <100 cm{sup 3}, and {>=}100 cm{sup 3} groups was 90%, 83%, and 85%, respectively (p = 0.18). To adjust for other potential variables affecting bRFS rates, a multivariate time-to-failure analysis using the Cox proportional hazards model was performed. Rectal distention was not an independent predictor of biochemical failure on multivariate analysis (p = 0.80). Rectal distention was not a predictor of rectal or urinary toxicity. Conclusion: The use of daily image guidance eliminates errors such as rectal distention at the initial planning stage that can affect outcomes after radiotherapy for localized prostate cancer.

  6. Complementary and Alternative Medicine use, Patient Reported Outcomes, and Treatment Satisfaction among Men with Localized Prostate Cancer

    PubMed Central

    Ramsey, Scott D.; Zeliadt, Steven B.; Blough, David K.; Fedorenko, Catherine R.; Fairweather, Megan E.; McDermott, Cara L.; Penson, David F.; Van Den Eeden, Stephen K.; Hamilton, Ann S.; Arora, Neeraj K.

    2012-01-01

    Objectives We sought to evaluate the association between complementary and alternative medicine (CAM) use, satisfaction with treatment, and patient-reported outcomes following treatment. Methods The Prostate CAncer Therapy Selection Study (PCATS) prospectively surveyed patients newly diagnosed with localized prostate cancer about their treatment decision making process and outcomes. The PCATS study recruited patients in three geographic areas through hospital-based urology clinics and community urology practices. Results More than 700 patients completed the baseline and follow-up surveys. More than 50% of respondents reported using CAM, 39% if prayer was excluded as a type of CAM. In multivariate analysis, factors related to communication with the treating physician, but not CAM use, were associated with treatment satisfaction. The likelihood of stability or improvement in urinary, bowel, and sexual function at 6 months was related to the choice of primary therapy, but unrelated to CAM use. Conclusions In this prospective observational study, CAM use was highly prevalent but unrelated to treatment satisfaction or changes in functional status. The impact of CAM on these endpoints remains to be established in comparative effectiveness studies. PMID:22546381

  7. A clinical data validated mathematical model of prostate cancer growth under intermittent androgen suppression therapy

    NASA Astrophysics Data System (ADS)

    Portz, Travis; Kuang, Yang; Nagy, John D.

    2012-03-01

    Prostate cancer is commonly treated by a form of hormone therapy called androgen suppression. This form of treatment, while successful at reducing the cancer cell population, adversely affects quality of life and typically leads to a recurrence of the cancer in an androgen-independent form. Intermittent androgen suppression aims to alleviate some of these adverse affects by cycling the patient on and off treatment. Clinical studies have suggested that intermittent therapy is capable of maintaining androgen dependence over multiple treatment cycles while increasing quality of life during off-treatment periods. This paper presents a mathematical model of prostate cancer to study the dynamics of androgen suppression therapy and the production of prostate-specific antigen (PSA), a clinical marker for prostate cancer. Preliminary models were based on the assumption of an androgen-independent (AI) cell population with constant net growth rate. These models gave poor accuracy when fitting clinical data during simulation. The final model presented hypothesizes an AI population with increased sensitivity to low levels of androgen. It also hypothesizes that PSA production is heavily dependent on androgen. The high level of accuracy in fitting clinical data with this model appears to confirm these hypotheses, which are also consistent with biological evidence.

  8. Volumetric-modulated arc therapy planning using multicriteria optimization for localized prostate cancer.

    PubMed

    Ghandour, Sarah; Matzinger, Oscar; Pachoud, Marc

    2015-05-08

    The purpose of this work is to evaluate the volumetric-modulated arc therapy (VMAT) multicriteria optimization (MCO) algorithm clinically available in the RayStation treatment planning system (TPS) and its ability to reduce treatment planning time while providing high dosimetric plan quality. Nine patients with localized prostate cancer who were previously treated with 78 Gy in 39 fractions using VMAT plans and rayArc system based on the direct machine parameter optimization (DMPO) algorithm were selected and replanned using the VMAT-MCO system. First, the dosimetric quality of the plans was evaluated using multiple conformity metrics that account for target coverage and sparing of healthy tissue, used in our departmental clinical protocols. The conformity and homogeneity index, number of monitor units, and treatment planning time for both modalities were assessed. Next, the effects of the technical plan parameters, such as constraint leaf motion CLM (cm/°) and maximum arc delivery time T (s), on the accuracy of delivered dose were evaluated using quality assurance passing rates (QAs) measured using the Delta4 phantom from ScandiDos. For the dosimetric plan's quality analysis, the results show that the VMAT-MCO system provides plans comparable to the rayArc system with no statistical difference for V95% (p < 0.01), D1% (p < 0.01), CI (p < 0.01), and HI (p < 0.01) of the PTV, bladder (p < 0.01), and rectum (p < 0.01) constraints, except for the femoral heads and healthy tissues, for which a dose reduction was observed using MCO compared with rayArc (p < 0.01). The technical parameter study showed that a combination of CLM equal to 0.5 cm/degree and a maximum delivery time of 72 s allowed the accurate delivery of the VMAT-MCO plan on the Elekta Versa HD linear accelerator. Planning evaluation and dosimetric measurements showed that VMAT-MCO can be used clinically with the advantage of enhanced planning process efficiency by reducing the treatment planning time

  9. Kilovoltage Intrafraction Monitoring for Prostate Intensity Modulated Arc Therapy: First Clinical Results

    SciTech Connect

    Ng, Jin Aun; Booth, Jeremy T.; Poulsen, Per R.; Fledelius, Walther; Worm, Esben Schjodt; Eade, Thomas; Hegi, Fiona; Kneebone, Andrew; Kuncic, Zdenka; Keall, Paul J.

    2012-12-01

    Purpose: Most linear accelerators purchased today are equipped with a gantry-mounted kilovoltage X-ray imager which is typically used for patient imaging prior to therapy. A novel application of the X-ray system is kilovoltage intrafraction monitoring (KIM), in which the 3-dimensional (3D) tumor position is determined during treatment. In this paper, we report on the first use of KIM in a prospective clinical study of prostate cancer patients undergoing intensity modulated arc therapy (IMAT). Methods and Materials: Ten prostate cancer patients with implanted fiducial markers undergoing conventionally fractionated IMAT (RapidArc) were enrolled in an ethics-approved study of KIM. KIM involves acquiring kV images as the gantry rotates around the patient during treatment. Post-treatment, markers in these images were segmented to obtain 2D positions. From the 2D positions, a maximum likelihood estimation of a probability density function was used to obtain 3D prostate trajectories. The trajectories were analyzed to determine the motion type and the percentage of time the prostate was displaced {>=}3, 5, 7, and 10 mm. Independent verification of KIM positional accuracy was performed using kV/MV triangulation. Results: KIM was performed for 268 fractions. Various prostate trajectories were observed (ie, continuous target drift, transient excursion, stable target position, persistent excursion, high-frequency excursions, and erratic behavior). For all patients, 3D displacements of {>=}3, 5, 7, and 10 mm were observed 5.6%, 2.2%, 0.7% and 0.4% of the time, respectively. The average systematic accuracy of KIM was measured at 0.46 mm. Conclusions: KIM for prostate IMAT was successfully implemented clinically for the first time. Key advantages of this method are (1) submillimeter accuracy, (2) widespread applicability, and (3) a low barrier to clinical implementation. A disadvantage is that KIM delivers additional imaging dose to the patient.

  10. Unraveling Brazilian Indian population prostate good health: clinical, anthropometric and genetic features

    PubMed Central

    de Lima, Mario M.; Reis, Leonardo O.; Ferreira, Ubirajara; Cardoso, Ulieme Oliveira; Barbieri, Raquel Bueno; de Mendonça, Gustavo B.; Ward, Laura S.

    2015-01-01

    Purpose To compare dietary, lifestyle, clinical, anthropometric, genetic and prostatic features of Brazilian Indians and non-Indians (Amazon). Methods 315 men, 228 Indians and 89 non-Indians, ≥40 years old were submitted to digital rectal examination, serum prostate specific antigen (PSA), testosterone, TP53 and GSTP1 genotyping, anthropometric, lifestyle, dietary, personal and familial medical history. Prostatic symptoms were evaluated with the International Prostate Symptom Score (IPSS). Results Macuxis and Yanomamis represented 43.6% and 14.5% of Indians respectively who spontaneously referred no prostate symptoms. Mean IPSS was 7, range 3-19, with only 15% of moderate symptoms (score 8-19); Mean age was 54.7 years, waist circumference 86.6 cm, BMI 23.9 kg/m2. Yanomamis presented both lower BMI (21.4 versus 24.8 and 23.3, p=0,001) and prostate volume than Macuxis and “other ethnic groups” (15 versus 20, p=0.001). Testosterone (414 versus 502 and 512, p=0.207) and PSA (0.48 versus 0.6 and 0.41, p=0.349) were similar with progressive PSA increase with aging. Val/Val correlated with lower PSA (p=0.0361). Indians compared to control population presented: - TP53 super representation of Arg/Arg haplotype, 74.5% versus 42.5%, p<0.0001. -GSTP1 Ile/Ile 35.3% versus 60.9%; Ile/Val 45.9% versus 28.7%; Val/Val 18.8% versus 10.3%; p=0.0003. Conclusions Observed specific dietary, lifestyle, anthropometric and genetic profile for TP53 and GSTP1 may contribute to Brazilian Indian population prostate good health. PMID:26005978

  11. Correlation of HOXD3 promoter hypermethylation with clinical and pathologic features in screening prostate biopsies

    PubMed Central

    Chen, Leonard N; Rubin, Rachel S; Othepa, Eugide; Cer, Caroline; Yun, Elizabeth; Agarwal, Raghunath P; Collins, Brian T; McGeagh, Kevin; Pahira, John; Bandi, Guarav; Kowalczyk, Keith; Kumar, Deepak; Dritschilo, Anatoly; Collins, Sean P; Bostwick, David G; Lynch, John H; Suy, Simeng

    2014-01-01

    BACKGROUND Molecular markers that can discriminate indolent cancers from aggressive ones may improve the management of prostate cancer and minimize unnecessary treatment. Aberrant DNA methylation is a common epigenetic event in cancers and HOXD3 promoter hypermethylation (H3PH) has been found in prostate cancer. Our objective was to evaluate the relationship between H3PH and clinicopathologic features in screening prostate biopsies. METHODS Ninety-two patients who underwent a prostate biopsy at our institution between October 2011 and May 2012 were included in this study. The core with the greatest percentage of the highest grade disease was analyzed for H3PH by methylation-specific PCR. Correlational analysis was used to analyze the relationship between H3PH and various clinical parameters. Chi-square analysis was used to compare H3PH status between benign and malignant disease. RESULTS Of the 80 biopsies with HOXD3 methylation status assessable, 66 sets were confirmed to have cancer. In the 14 biopsies with benign disease there was minimal H3PH with the mean percentage of methylation reference (PMR) of 0.7%. In contrast, the HOXD3 promoter was hypermethylated in 16.7% of all cancers and in 50% of high risk tumors with an average PMR of 4.3% (P = 0.008). H3PH was significantly correlated with age (P = 0.013), Gleason score (P = 0.031) and the maximum involvement of the biopsy core (P = 0.035). CONCLUSIONS H3PH is associated with clinicopathologic features. The data indicate that H3PH is more common in older higher risk patients. More research is needed to determine the role of this marker in optimizing management strategies in men with newly diagnosed prostate cancer. Prostate 74:714–721, 2014. © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID:24847526

  12. Treatment profile and complications associated with cryotherapy for localized prostate cancer: A population-based study

    PubMed Central

    Roberts, Calpurnyia B.; Jang, Thomas L.; Shao, Yu-Hsuan; Kabadi, Shaum; Moore, Dirk F.; Lu-Yao, Grace L.

    2011-01-01

    The aim of this study was to assess the treatment patterns and 3 to 12-month complication rates associated with receiving prostate cryotherapy in a population-based study. Men > 65 years diagnosed with incident localized prostate cancer in Surveillance Epidemiology End Results (SEER) - Medicare linked database from 2004 to 2005 were identified. A total of 21,344 men were included in the study, of which 380 were treated initially with cryotherapy. Recipients of cryotherapy versus aggressive forms of prostate therapy (i.e. radical prostatectomy or radiation therapy) were more likely to be older, have one co-morbidity, low income, live in the South, and be diagnosed with indolent cancer. Complication rates increased from 3 to 12 months following cryotherapy. By the twelfth month, the rates for urinary incontinence, lower urinary tract obstruction, erectile dysfunction, and bowel bleeding reached 9.8%, 28.7%, 20.1%, and 3.3%, respectively. Diagnoses of hydronephrosis, urinary fistula, or bowel fistula were not evident. The rates of corrective invasive procedures for lower urinary tract obstruction and erectile dysfunction were both <2.9% by the twelfth month. Overall, complications post cryotherapy were modest; however, diagnoses for lower urinary tract obstruction and erectile dysfunction were common. PMID:21519347

  13. ERG rearrangement as a novel marker for predicting the extra-prostatic extension of clinically localised prostate cancer

    PubMed Central

    LU, LI; ZHANG, HAO; PANG, JUN; HOU, GUO-LIANG; LU, MIN-HUA; GAO, XIN

    2016-01-01

    Currently, there are no well-established preoperative clinicopathological parameters for predicting extra-prostatic extension (EPE) in patients with clinically localised prostate cancer (PCa). The transmembrane protease serine 2 (TMPRSS2)-ETS-related gene (ERG) fusion gene is a specific biomarker of PCa and is considered a prognostic predictor. The aim of the present study was to assess the value of this marker for predicting EPE in patients with clinically localised PCa. In total, 306 PCa patients with clinically localised disease, including 220 patients (71.9%) with organ-confined disease and 86 EPE cases (28.1%), were included in the study. Receiver operating characteristic curves and logistic regression were employed to establish the optimal cut-off value and to investigate whether ERG rearrangement was an independent predictor for the EPE of clinically localised PCa. A leave-one-out cross-validation (LOOCV) model was implemented to validate the predictive power of ERG rearrangement. An increase in ERG rearrangements was identified to be associate'd with EPE, and the optimal cut-off for predicting EPE was determined to be 2.25%, with a sensitivity of 70.24% [95% confidence interval (CI), 62.6–78.9%], a specificity of 80.43% (95% CI, 75.4–85.1%), and an area under the curve (AUC) of 0.781 (95% CI, 0.730–0.826). In the LOOCV model, ERG rearrangement also demonstrated good performance for predicting EPE (sensitivity, 76.923%; specificity, 71.429%; 95% CI for AUC, 0.724–0.958). In addition, a high Gleason score (≥7) and a cT2c classification upon biopsy were independent factors for EPE. PMID:27073512

  14. Clinical Application of Circulating Tumour Cells in Prostate Cancer: From Bench to Bedside and Back

    PubMed Central

    León-Mateos, Luis; Vieito, María; Anido, Urbano; López López, Rafael; Muinelo Romay, Laura

    2016-01-01

    Prostate cancer is the most common cancer in men worldwide. To improve future drug development and patient management, surrogate biomarkers associated with relevant outcomes are required. Circulating tumour cells (CTCs) are tumour cells that can enter the circulatory system, and are principally responsible for the development of metastasis at distant sites. In recent years, interest in detecting CTCs as a surrogate biomarker has ghiiukjrown. Clinical studies have revealed that high levels of CTCs in the blood correlate with disease progression in patients with prostate cancer; however, their predictive value for monitoring therapeutic response is less clear. Despite the important progress in CTC clinical development, there are critical requirements for the implementation of their analysis as a routine oncology tool. The goal of the present review is to provide an update on the advances in the clinical validation of CTCs as a surrogate biomarker and to discuss the principal obstacles and main challenges to their inclusion in clinical practice. PMID:27657044

  15. Using circulating tumor cells to inform on prostate cancer biology and clinical utility

    PubMed Central

    Li, Jing; Gregory, Simon G.; Garcia-Blanco, Mariano A.; Armstrong, Andrew J.

    2016-01-01

    Substantial advances in the molecular biology of prostate cancer have led to the approval of multiple new systemic agents to treat men with metastatic castration-resistant prostate cancer (mCRPC). These treatments encompass androgen receptor directed therapies, immunotherapies, bone targeting radiopharmaceuticals and cytotoxic chemotherapies. There is, however, great heterogeneity in the degree of patient benefit with these agents, thus fueling the need to develop predictive biomarkers that are able to rationally guide therapy. Circulating tumor cells (CTCs) have the potential to provide an assessment of tumor-specific biomarkers through a non-invasive, repeatable “liquid biopsy” of a patient’s cancer at a given point in time. CTCs have been extensively studied in men with mCRPC, where CTC enumeration using the Cellsearch® method has been validated and FDA approved to be used in conjunction with other clinical parameters as a prognostic biomarker in metastatic prostate cancer. In addition to enumeration, more sophisticated molecular profiling of CTCs is now feasible and may provide more clinical utility as it may reflect tumor evolution within an individual particularly under the pressure of systemic therapies. Here, we review technologies used to detect and characterize CTCs, and the potential biological and clinical utility of CTC molecular profiling in men with metastatic prostate cancer. PMID:26079252

  16. Immunochemical Assays and Nucleic-Acid Detection Techniques for Clinical Diagnosis of Prostate Cancer

    PubMed Central

    Kanyong, Prosper; Rawlinson, Sean; Davis, James

    2016-01-01

    Prostate cancer (PCa) is a significant cause of morbidity and mortality and the most common cancer in men in Europe, North America, and some parts of Africa. The established methods for detecting PCa are normally based on tests using Prostate Specific Antigen (PSA) in blood, Prostate cancer antigen 3 (PCA3) in urine and tissue Alpha-methylacyl-CoA racemase (AMACR) as tumour markers in patient samples. Prior to the introduction of PSA in clinics, prostatic acid phosphatase (PAP) was the most widely used biomarker. An early diagnosis of PCa through the detection of these biomarkers requires the availability of simple, reliable, cost-effective and robust techniques. Immunoassays and nucleic acid detection techniques have experienced unprecedented growth in recent years and seem to be the most promising analytical tools. This growth has been driven in part by the surge in demand for near-patient-testing systems in clinical diagnosis. This article reviews immunochemical assays, and nucleic-acid detection techniques that have been used to clinically diagnose PCa. PMID:26958088

  17. Decision support system for localizing prostate cancer based on multiparametric magnetic resonance imaging

    PubMed Central

    Shah, Vijay; Turkbey, Baris; Mani, Haresh; Pang, Yuxi; Pohida, Thomas; Merino, Maria J.; Pinto, Peter A.; Choyke, Peter L.; Bernardo, Marcelino

    2012-01-01

    Purpose: There is a growing need to localize prostate cancers on magnetic resonance imaging (MRI) to facilitate the use of image guided biopsy, focal therapy, and active surveillance follow up. Our goal was to develop a decision support system (DSS) for detecting and localizing peripheral zone prostate cancers by using machine learning approach to calculate a cancer probability map from multiparametric MR images (MP-MRI). Methods: This IRB approved Health Insurance Portability and Accountability Act compliant retrospective study consisted of 31 patients (mean age and serum prostate specific antigen of 60.4 and 6.62 ng/ml, respectively) who had MP-MRI at 3 T followed by radical prostatectomy. Seven patients were excluded due to technical issues with their MP-MRI (e.g., motion artifact, failure to perform all sequences). Cancer and normal regions were identified in the peripheral zone by correlating them to whole mount histology slides of the excised prostatectomy specimens. To facilitate the correlation, tissue blocks matching the MR slices were obtained using a MR-based patient-specific mold. Segmented regions on the MP-MRI were correlated to histopathology and used as training sets for the learning system that generated the cancer probability maps. Leave-one-patient-out cross-validation on the cancer and normal regions was performed to determine the learning system's efficacy, an evolutionary strategies approach (also known as a genetic algorithm) was used to find the optimal values for a set of parameters, and finally a cancer probability map was generated. Results: For the 24 patients that were used in the study, 225 cancer and 264 noncancerous regions were identified from the region maps. The efficacy of DSS was first determined without optimizing support vector machines (SVM) parameters, where a region having a cancer probability greater than or equal to 50% was considered as a correct classification. The nonoptimized system had an f-measure of 85% and the

  18. Current Status of Prostate-Specific Membrane Antigen Targeting in Nuclear Medicine: Clinical Translation of Chelator Containing Prostate-Specific Membrane Antigen Ligands Into Diagnostics and Therapy for Prostate Cancer.

    PubMed

    Kratochwil, Clemens; Afshar-Oromieh, Ali; Kopka, Klaus; Haberkorn, Uwe; Giesel, Frederik L

    2016-09-01

    The prostate-specific membrane antigen (PSMA) is expressed by approximately 90% of prostate carcinomas. The expression correlates with unfavorable prognostic factors, such as a high Gleason score, infiltrative growth, metastasis, and hormone-independence. The high specificity, especially in the undifferentiated stage, makes it an excellent target for diagnosis and therapy. Therefore, antibodies and small molecule inhibitors have been developed for imaging and therapy. In 2011 PSMA-11, a ligand that consists of the Glu-urea-motif and the chelator HBED-CC, which can be exclusively radiolabeled with (68)Ga for PET imaging, presented the clinical breakthrough for prostate cancer diagnostics. In two large diagnostic studies (n = 319 and n = 248) PET/CT with PSMA-11 successfully localized the recurrent tumor in approximately 90% of patients with biochemical relapse. Integrating PSMA-PET/CT into the planning phase of radiotherapy, the treatment concept is changed in 30%-50% of the patients. The combination of the Glu-urea-motif with DOTA, which can be labeled with several diagnostic and therapeutic radionuclides, opened new avenues for therapeutic usage of the small-molecule PSMA ligands. In the beginning of 2016, there are four confirmative reports (n = 19, n = 24, n = 30, and n = 56) from four different centers reporting a PSA response in approximately 70% of patients treated with (177)Lu-labeled PSMA ligands. In conclusion, the data available up to now indicate a widespread use of PSMA ligands for diagnostic applications with respect to staging, detection of recurrence, or metastases in patients with rising tumor markers and for therapy in case of failure of guideline-compliant treatment. PMID:27553466

  19. Complications associated with preoperative radiation therapy and Iodine-125 brachytherapy for localized prostatic carcinoma

    SciTech Connect

    Flanigan, R.C.; Patterson, J.; Mendiondo, O.A.; Gee, W.F.; Lucas, B.A.; McRoberts, J.W.

    1983-08-01

    Twenty-five consecutive patients with localized adenocarcinoma of the prostate treated with 1,050 rad preoperative radiation therapy and Iodine-125 seed brachytherapy are reviewed. Significant long-term postoperative complications included radiation cystitis (12%), radiation proctitis (4%), genital and leg edema (12%), stress incontinence (8%), total incontinence (4%), and impotence (26%). Complications occurred in 75 per cent of patients who received additional postoperative radiation. Improved staging with CT scan, lymphangiography, and Chiba needle biopsy of any possibly abnormal lymph nodes provided excellent preoperative staging with only 1 patient (6%) upstaged at surgery to Stage D1.

  20. CMDX©-based single source information system for simplified quality management and clinical research in prostate cancer

    PubMed Central

    2012-01-01

    Background Histopathological evaluation of prostatectomy specimens is crucial to decision-making and prediction of patient outcomes in prostate cancer (PCa). Topographical information regarding PCa extension and positive surgical margins (PSM) is essential for clinical routines, quality assessment, and research. However, local hospital information systems (HIS) often do not support the documentation of such information. Therefore, we investigated the feasibility of integrating a cMDX-based pathology report including topographical information into the clinical routine with the aims of obtaining data, performing analysis and generating heat maps in a timely manner, while avoiding data redundancy. Methods We analyzed the workflow of the histopathological evaluation documentation process. We then developed a concept for a pathology report based on a cMDX data model facilitating the topographical documentation of PCa and PSM; the cMDX SSIS is implemented within the HIS of University Hospital Muenster. We then generated a heat map of PCa extension and PSM using the data. Data quality was assessed by measuring the data completeness of reports for all cases, as well as the source-to-database error. We also conducted a prospective study to compare our proposed method with recent retrospective and paper-based studies according to the time required for data analysis. Results We identified 30 input fields that were applied to the cMDX-based data model and the electronic report was integrated into the clinical workflow. Between 2010 and 2011, a total of 259 reports were generated with 100% data completeness and a source-to-database error of 10.3 per 10,000 fields. These reports were directly reused for data analysis, and a heat map based on the data was generated. PCa was mostly localized in the peripheral zone of the prostate. The mean relative tumor volume was 16.6%. The most PSM were localized in the apical region of the prostate. In the retrospective study, 1623 paper

  1. Planning Target Margin Calculations for Prostate Radiotherapy Based on Intrafraction and Interfraction Motion Using Four Localization Methods

    SciTech Connect

    Beltran, Chris Herman, Michael G.; Davis, Brian J.

    2008-01-01

    Purpose: To determine planning target volume (PTV) margins for prostate radiotherapy based on the internal margin (IM) (intrafractional motion) and the setup margin (SM) (interfractional motion) for four daily localization methods: skin marks (tattoo), pelvic bony anatomy (bone), intraprostatic gold seeds using a 5-mm action threshold, and using no threshold. Methods and Materials: Forty prostate cancer patients were treated with external radiotherapy according to an online localization protocol using four intraprostatic gold seeds and electronic portal images (EPIs). Daily localization and treatment EPIs were obtained. These data allowed inter- and intrafractional analysis of prostate motion. The SM for the four daily localization methods and the IM were determined. Results: A total of 1532 fractions were analyzed. Tattoo localization requires a SM of 6.8 mm left-right (LR), 7.2 mm inferior-superior (IS), and 9.8 mm anterior-posterior (AP). Bone localization requires 3.1, 8.9, and 10.7 mm, respectively. The 5-mm threshold localization requires 4.0, 3.9, and 3.7 mm. No threshold localization requires 3.4, 3.2, and 3.2 mm. The intrafractional prostate motion requires an IM of 2.4 mm LR, 3.4 mm IS and AP. The PTV margin using the 5-mm threshold, including interobserver uncertainty, IM, and SM, is 4.8 mm LR, 5.4 mm IS, and 5.2 mm AP. Conclusions: Localization based on EPI with implanted gold seeds allows a large PTV margin reduction when compared with tattoo localization. Except for the LR direction, bony anatomy localization does not decrease the margins compared with tattoo localization. Intrafractional prostate motion is a limiting factor on margin reduction.

  2. Multidrug resistance protein 1 localization in lipid raft domains and prostasomes in prostate cancer cell lines

    PubMed Central

    Gomà, Alba; Mir, Roser; Martínez-Soler, Fina; Tortosa, Avelina; Vidal, August; Condom, Enric; Pérez–Tomás, Ricardo; Giménez-Bonafé, Pepita

    2014-01-01

    Background One of the problems in prostate cancer (CaP) treatment is the appearance of the multidrug resistance phenotype, in which ATP-binding cassette transporters such as multidrug resistance protein 1 (MRP1) play a role. Different localizations of the transporter have been reported, some of them related to the chemoresistant phenotype. Aim This study aimed to compare the localization of MRP1 in three prostate cell lines (normal, androgen-sensitive, and androgen-independent) in order to understand its possible role in CaP chemoresistance. Methods MRP1 and caveolae protein markers were detected using confocal microscopy, performing colocalization techniques. Lipid raft isolation made it possible to detect these proteins by Western blot analysis. Caveolae and prostasomes were identified by electron microscopy. Results We show that MRP1 is found in lipid raft fractions of tumor cells and that the number of caveolae increases with malignancy acquisition. MRP1 is found not only in the plasma membrane associated with lipid rafts but also in cytoplasmic accumulations colocalizing with the prostasome markers Caveolin-1 and CD59, suggesting that in CaP cells, MRP1 is localized in prostasomes. Conclusion We hypothesize that the presence of MRP1 in prostasomes could serve as a reservoir of MRP1; thus, taking advantage of the release of their content, MRP1 could be translocated to the plasma membrane contributing to the chemoresistant phenotype. The presence of MRP1 in prostasomes could serve as a predictor of malignancy in CaP. PMID:25525371

  3. Identifying Clinically Significant Prostate Cancers using 3-D In Vivo Acoustic Radiation Force Impulse Imaging with Whole-Mount Histology Validation.

    PubMed

    Palmeri, Mark L; Glass, Tyler J; Miller, Zachary A; Rosenzweig, Stephen J; Buck, Andrew; Polascik, Thomas J; Gupta, Rajan T; Brown, Alison F; Madden, John; Nightingale, Kathryn R

    2016-06-01

    Overly aggressive prostate cancer (PCa) treatment adversely affects patients and places an unnecessary burden on our health care system. The inability to identify and grade clinically significant PCa lesions is a factor contributing to excessively aggressive PCa treatment, such as radical prostatectomy, instead of more focal, prostate-sparing procedures such as cryotherapy and high-dose radiation therapy. We have performed 3-D in vivo B-mode and acoustic radiation force impulse (ARFI) imaging using a mechanically rotated, side-fire endorectal imaging array to identify regions suspicious for PCa in 29 patients being treated with radical prostatectomies for biopsy-confirmed PCa. Whole-mount histopathology analyses were performed to identify regions of clinically significant/insignificant PCa lesions, atrophy and benign prostatic hyperplasia. Regions of suspicion for PCa were reader-identified in ARFI images based on boundary delineation, contrast, texture and location. These regions of suspicion were compared with histopathology identified lesions using a nearest-neighbor regional localization approach. Of all clinically significant lesions identified on histopathology, 71.4% were also identified using ARFI imaging, including 79.3% of posterior and 33.3% of anterior lesions. Among the ARFI-identified lesions, 79.3% corresponded to clinically significant PCa lesions, with these lesions having higher indices of suspicion than clinically insignificant PCa. ARFI imaging had greater sensitivity for posterior versus anterior lesions because of greater displacement signal-to-noise ratio and finer spatial sampling. Atrophy and benign prostatic hyperplasia can cause appreciable prostate anatomy distortion and heterogeneity that confounds ARFI PCa lesion identification; however, in general, ARFI regions of suspicion did not coincide with these benign pathologies. PMID:26947445

  4. Hypoxic Prostate/Muscle PO{sub 2} Ratio Predicts for Outcome in Patients With Localized Prostate Cancer: Long-Term Results

    SciTech Connect

    Turaka, Aruna; Buyyounouski, Mark K.; Hanlon, Alexandra L.; Horwitz, Eric M.; Greenberg, Richard E.; Movsas, Benjamin

    2012-03-01

    Purpose: To correlate tumor oxygenation status with long-term biochemical outcome after prostate brachytherapy. Methods and Materials: Custom-made Eppendorf PO{sub 2} microelectrodes were used to obtain PO{sub 2} measurements from the prostate (P), focused on positive biopsy locations, and normal muscle tissue (M), as a control. A total of 11,516 measurements were obtained in 57 men with localized prostate cancer immediately before prostate brachytherapy was given. The Eppendorf histograms provided the median PO{sub 2}, mean PO{sub 2}, and % <5 mm Hg or <10 mm Hg. Biochemical failure (BF) was defined using both the former American Society of Therapeutic Radiation Oncology (ASTRO) (three consecutive raises) and the current Phoenix (prostate-specific antigen nadir + 2 ng/mL) definitions. A Cox proportional hazards regression model evaluated the influence of hypoxia using the P/M mean PO{sub 2} ratio on BF. Results: With a median follow-up time of 8 years, 12 men had ASTRO BF and 8 had Phoenix BF. On multivariate analysis, P/M PO{sub 2} ratio <0.10 emerged as the only significant predictor of ASTRO BF (p = 0.043). Hormonal therapy (p = 0.015) and P/M PO{sub 2} ratio <0.10 (p = 0.046) emerged as the only independent predictors of the Phoenix BF. Kaplan-Meier freedom from BF for P/M ratio <0.10 vs. {>=}0.10 at 8 years for ASTRO BF was 46% vs. 78% (p = 0.03) and for the Phoenix BF was 66% vs. 83% (p = 0.02). Conclusions: Hypoxia in prostate cancer (low mean P/M PO{sub 2} ratio) significantly predicts for poor long-term biochemical outcome, suggesting that novel hypoxic strategies should be investigated.

  5. Locally-constrained boundary regression for segmentation of prostate and rectum in the planning CT images.

    PubMed

    Shao, Yeqin; Gao, Yaozong; Wang, Qian; Yang, Xin; Shen, Dinggang

    2015-12-01

    Automatic and accurate segmentation of the prostate and rectum in planning CT images is a challenging task due to low image contrast, unpredictable organ (relative) position, and uncertain existence of bowel gas across different patients. Recently, regression forest was adopted for organ deformable segmentation on 2D medical images by training one landmark detector for each point on the shape model. However, it seems impractical for regression forest to guide 3D deformable segmentation as a landmark detector, due to large number of vertices in the 3D shape model as well as the difficulty in building accurate 3D vertex correspondence for each landmark detector. In this paper, we propose a novel boundary detection method by exploiting the power of regression forest for prostate and rectum segmentation. The contributions of this paper are as follows: (1) we introduce regression forest as a local boundary regressor to vote the entire boundary of a target organ, which avoids training a large number of landmark detectors and building an accurate 3D vertex correspondence for each landmark detector; (2) an auto-context model is integrated with regression forest to improve the accuracy of the boundary regression; (3) we further combine a deformable segmentation method with the proposed local boundary regressor for the final organ segmentation by integrating organ shape priors. Our method is evaluated on a planning CT image dataset with 70 images from 70 different patients. The experimental results show that our proposed boundary regression method outperforms the conventional boundary classification method in guiding the deformable model for prostate and rectum segmentations. Compared with other state-of-the-art methods, our method also shows a competitive performance. PMID:26439938

  6. Clinical development of a failure detection-based online repositioning strategy for prostate IMRT—Experiments, simulation, and dosimetry study

    PubMed Central

    Liu, Wu; Qian, Jianguo; Hancock, Steven L.; Xing, Lei; Luxton, Gary

    2010-01-01

    Purpose: To implement and evaluate clinic-ready adaptive imaging protocols for online patient repositioning (motion tracking) during prostate IMRT using treatment beam imaging supplemented by minimal, as-needed use of on-board kV. Methods: The authors examine the two-step decision-making strategy: (1) Use cine-MV imaging and online-updated characterization of prostate motion to detect target motion that is potentially beyond a predefined threshold and (2) use paired MV-kV 3D localization to determine overthreshold displacement and, if needed, reposition the patient. Two levels of clinical implementation were evaluated: (1) Field-by-field based motion correction for present-day linacs and (2) instantaneous repositioning for new-generation linacs with capabilities of simultaneous MV-kV imaging and remote automatic couch control during treatment delivery. Experiments were performed on a Varian Trilogy linac in clinical mode using a 4D motion phantom programed with prostate motion trajectories taken from patient data. Dosimetric impact was examined using a 2D ion chamber array. Simulations were done for 536 trajectories from 17 patients. Results: Despite the loss of marker detection efficiency caused by the MLC leaves sometimes obscuring the field at the marker’s projected position on the MV imager, the field-by-field correction halved (from 23% to 10%) the mean percentage of time that target displacement exceeded a 3 mm threshold, as compared to no intervention. This was achieved at minimal cost in additional imaging (average of one MV-kV pair per two to three treatment fractions) and with a very small number of repositionings (once every four to five fractions). Also with low kV usage (∼2∕fraction), the instantaneous repositioning approach reduced overthreshold time by more than 75% (23% to 5%) even with severe MLC blockage as often encountered in current IMRT and could reduce the overthreshold time tenfold (to <2%) if the MLC blockage problem were relieved

  7. A Double-Blind Placebo-Controlled Randomized Clinical Trial With Magnesium Oxide to Reduce Intrafraction Prostate Motion for Prostate Cancer Radiotherapy

    SciTech Connect

    Lips, Irene M.; Gils, Carla H. van; Kotte, Alexis N.T.J.; Leerdam, Monique E. van; Franken, Stefan P.G.; Heide, Uulke A. van der; Vulpen, Marco van

    2012-06-01

    Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in {>=}50% of the fractions an intrafraction motion outside a range of 2 mm. Secondary outcome measures included quality of life and acute toxicity. Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.

  8. Improving prostate cancer detection in veterans through the development of a clinical decision rule for prostate biopsy

    PubMed Central

    2013-01-01

    Background We sought to improve prostate cancer (PC) detection through developing a prostate biopsy clinical decision rule (PBCDR), based on an elevated PSA and laboratory biomarkers. This decision rule could be used after initial PC screening, providing the patient and clinician information to consider prior to biopsy. Methods This case–control study evaluated men from the Tampa, Florida, James A. Haley (JH) Veteran’s Administration (VA) (N = 1,378), from January 1, 1998, through April 15, 2005. To assess the PBCDR we did all of the following: 1) Identified biomarkers that are related to PC and have the capability of improving the efficiency of PC screening; 2) Developed statistical models to determine which can best predict the probability of PC; 3) Compared each potential model to PSA alone using Receiver Operator Characteristic (ROC) curves, to evaluate for improved overall effectiveness in PC detection and reduction in (negative) biopsies; and 4) Evaluated dose–response relationships between specified lab biomarkers (surrogates for extra-prostatic disease development) and PC progression. Results The following biomarkers were related to PC: hemoglobin (HGB) (OR = 1.42 95% CI 1.27, 1.59); red blood cell (RBC) count (OR = 2.52 95% CI 1.67, 3.78); PSA (OR = 1.04 95% CI 1.03, 1.05); and, creatinine (OR = 1.55 95% CI 1.12, 2.15). Comparing all PC stages versus non-cancerous conditions, the ROC curve area under the curve (AUC) enlarged (increasing the probability of correctly classifying PC): PSA (alone) 0.59 (95% CI 0.55, 0.61); PBCDR model 0.68 (95% CI 0.65, 0.71), and the positive predictive value (PPV) increased: PSA 44.7%; PBCDR model 61.8%. Comparing PC (stages II, III, IV) vs. other, the ROC AUC increased: PSA (alone) 0.63 (95% CI 0.58, 0.66); PBCDR model 0.72 (95% CI 0.68, 0.75), and the PPV increased: 20.6% (PSA); PBCDR model 55.3%. Conclusions These results suggest evaluating certain common biomarkers in conjunction with PSA may improve PC prediction

  9. Shape based MRI prostate image segmentation using local information driven directional distance Bayesian method

    NASA Astrophysics Data System (ADS)

    Gao, Yi; Tannenbaum, Allen

    2010-03-01

    In this paper, we present a shape based segmentation methodology for magnetic resonance prostate images. We first propose a new way to represent shapes via the hyperbolic tangent of the signed distance function. This effectively corrects the drawbacks of the signed distance function and yields very reasonable results for the shape registration and learning. Secondly, under a Bayesian statistical framework, instead of computing the posterior using a uniform prior, a directional distance map is introduced in order to incorporate a priori knowledge of image content as well as the estimated center of target object. Essentially, the image is modeled as a Finsler manifold and the metric is computed out of the directional derivative of the image. Then the directional distance map is computed to suppress the posterior remote from the object center. Thirdly, in the posterior image, a localized region based cost functional is designed to drive the shape based segmentation. Such cost functional utilizes the local regional information and is robust to both image noise and remote/irrelevant disturbances. With these three major components, the entire shape based segmentation procedure is provided as a complete open source pipeline and is applied to magnetic resonance image (MRI) prostate data.

  10. Computer-aided diagnosis: detection and localization of prostate cancer within the peripheral zone.

    PubMed

    Rampun, Andrik; Chen, Zhili; Malcolm, Paul; Tiddeman, Bernie; Zwiggelaar, Reyer

    2016-05-01

    We propose a methodology for prostate cancer detection and localization within the peripheral zone based on combining multiple segmentation techniques. We extract four image features using Gaussian and median filters. Subsequently, we use each image feature separately to generate binary segmentations. Finally, we take the intersection of all four binary segmentations, incorporating a model of the peripheral zone, and perform erosion to remove small false-positive regions. The initial evaluation of this method is based on 275 MRI images from 37 patients, and 86% of the slices were classified correctly with 87% and 86% sensitivity and specificity achieved, respectively. This paper makes two contributions: firstly, a novel computer-aided diagnosis approach, which is based on combining multiple segmentation techniques using only a small number of simple image features, and secondly, the development of the proposed method and its application in prostate cancer detection and localization using a single MRI modality with the results comparable with the state-of-the-art multimodality and advanced computer vision methods in the literature. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Does Local Recurrence of Prostate Cancer After Radiation Therapy Occur at the Site of Primary Tumor? Results of a Longitudinal MRI and MRSI Study

    SciTech Connect

    Arrayeh, Elnasif; Westphalen, Antonio C.; Kurhanewicz, John; Roach, Mack; Jung, Adam J.; Carroll, Peter R.; Coakley, Fergus V.

    2012-04-01

    Purpose: To determine if local recurrence of prostate cancer after radiation therapy occurs at the same site as the primary tumor before treatment, using longitudinal magnetic resonance (MR) imaging and MR spectroscopic imaging to assess dominant tumor location. Methods and Materials: This retrospective study was HIPAA compliant and approved by our Committee on Human Research. We identified all patients in our institutional prostate cancer database (1996 onward) who underwent endorectal MR imaging and MR spectroscopic imaging before radiotherapy for biopsy-proven prostate cancer and again at least 2 years after radiotherapy (n = 124). Two radiologists recorded the presence, location, and size of unequivocal dominant tumor on pre- and postradiotherapy scans. Recurrent tumor was considered to be at the same location as the baseline tumor if at least 50% of the tumor location overlapped. Clinical and biopsy data were collected from all patients. Results: Nine patients had unequivocal dominant tumor on both pre- and postradiotherapy imaging, with mean pre- and postradiotherapy dominant tumor diameters of 1.8 cm (range, 1-2.2) and 1.9 cm (range, 1.4-2.6), respectively. The median follow-up interval was 7.3 years (range, 2.7-10.8). Dominant recurrent tumor was at the same location as dominant baseline tumor in 8 of 9 patients (89%). Conclusions: Local recurrence of prostate cancer after radiation usually occurs at the same site as the dominant primary tumor at baseline, suggesting supplementary focal therapy aimed at enhancing local tumor control would be a rational addition to management.

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

    SciTech Connect

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

    2010-03-09

    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 registered (Focus Surgery, Indianapolis, USA) devices. Thirty-three patients were treated with Sonablate registered 200 (S200) from 1999 to 2001, 406 patients with Sonablate registered 500 (S500) from 2001 to 2005, 200 patients with Sonablate registered 500 version 4 (V4) from 2005-2008 and 19 patients with Sonablate registered 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.

  13. Human prostatic tumor cells in culture produce growth and differentiation factors active on osteoblasts: a new biological and clinical parameter for prostatic carcinoma.

    PubMed

    Festuccia, C; Teti, A; Bianco, P; Guerra, F; Vicentini, C; Tennina, R; Villanova, I; Sciortino, G; Bologna, M

    1997-01-01

    Prostate cancer (PRCA) cells metastasize to bone with high frequency, inducing typical osteosclerotic lesions. To establish if local stimuli on the bone tissue may derive from metastatic colonies of prostatic origin, we evaluated the biologic activities secreted by human prostatic epithelium and effective on osteoblast-like cells in vitro. Supernatant from short-term tissue cultures of human prostatic tissue samples obtained from PRCA (35 cases) and benign prostatic hyperplasia (BPH, 12 cases) patients were applied to three models of cells with osteoblastic phenotype: two normal [rabbit osteoblasts (OB) and rat periosteal cells (PO)] and one transformed (human osteosarcoma cell line, MG63). Proliferative activity was monitored through enzymatic reduction of tetrazolium salts and expressed as relative mitogenic activities (RMA). Analysis of proliferation and alkaline phosphatase (ALP) activity, a marker of osteoblast function, demonstrates that conditioned media (CM) from PRCA cultures stimulate both growth and activity of osteoblast-like cells to a greater extent compared to CM from BPH. Furthermore, cell growth and activity of osteoblast-like cells are progressively increased by CM derived from patients with stage B (tumor confined within the prostate capsule), stage C (locally invasive tumor), and stage D (invasive tumor with distant metastasis) disease. One of the mechanisms potentially underlying the CM-stimulated effects on bone cells is associated with the urokinase (uPA) enzyme route, whose release progressively increases with the stage of disease. However, antibodies against uPA and p-aminobenzamidine (a low molecular weight urokinase inhibitor) treatment, which both inhibit the proliferative and differentiative effects induced by exogenous urokinase, partially slow down the effects of CM from PRCA tissue cultures, suggesting that additional factors are secreted by prostatic tumor cells in vitro. In conclusion, we show that the mitogenic and differentiative

  14. Short-Term Soy Isoflavone Intervention in Patients with Localized Prostate Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Hamilton-Reeves, Jill M.; Banerjee, Snigdha; Banerjee, Sushanta K.; Holzbeierlein, Jeffrey M.; Thrasher, J. Brantley; Kambhampati, Suman; Keighley, John; Van Veldhuizen, Peter

    2013-01-01

    Purpose We describe the effects of soy isoflavone consumption on prostate specific antigen (PSA), hormone levels, total cholesterol, and apoptosis in men with localized prostate cancer. Methodology/Principal Findings We conducted a double-blinded, randomized, placebo-controlled trial to examine the effect of soy isoflavone capsules (80 mg/d of total isoflavones, 51 mg/d aglucon units) on serum and tissue biomarkers in patients with localized prostate cancer. Eighty-six men were randomized to treatment with isoflavones (n = 42) or placebo (n = 44) for up to six weeks prior to scheduled prostatectomy. We performed microarray analysis using a targeted cell cycle regulation and apoptosis gene chip (GEArrayTM). Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol were analyzed at baseline, mid-point, and at the time of radical prostatectomy. In this preliminary analysis, 12 genes involved in cell cycle control and 9 genes involved in apoptosis were down-regulated in the treatment tumor tissues versus the placebo control. Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol in the isoflavone-treated group compared to men receiving placebo were not statistically significant. Conclusions/Significance These data suggest that short-term intake of soy isoflavones did not affect serum hormone levels, total cholesterol, or PSA. Trial Registration ClinicalTrials.gov NCT00255125 PMID:23874588

  15. Localized Prostate Cancer Detection with 18F FACBC PET/CT: Comparison with MR Imaging and Histopathologic Analysis

    PubMed Central

    Mena, Esther; Shih, Joanna; Pinto, Peter A.; Merino, Maria J.; Lindenberg, Maria L.; Bernardo, Marcelino; McKinney, Yolanda L.; Adler, Stephen; Owenius, Rikard; Choyke, Peter L.; Kurdziel, Karen A.

    2014-01-01

    Purpose To characterize uptake of 1-amino-3-fluorine 18-fluorocyclobutane-1-carboxylic acid (18F FACBC) in patients with localized prostate cancer, benign prostatic hyperplasia (BPH), and normal prostate tissue and to evaluate its potential utility in delineation of intraprostatic cancers in histopathologically confirmed localized prostate cancer in comparison with magnetic resonance (MR) imaging. Materials and Methods Institutional review board approval and written informed consent were obtained for this HIPAA-compliant prospective study. Twenty-one men underwent dynamic and static abdominopelvic 18F FACBC combined positron emission tomography (PET) and computed tomography (CT) and multiparametric (MP) 3-T endorectal MR imaging before robotic-assisted prostatectomy. PET/CT and MR images were coregistered by using pelvic bones as fiducial markers; this was followed by manual adjustments. Whole-mount histopathologic specimens were sliced with an MR-based patient-specific mold. 18F FACBC PET standardized uptake values (SUVs) were compared with those at MR imaging and histopathologic analysis for lesion- and sector-based (20 sectors per patient) analysis. Positive and negative predictive values for each modality were estimated by using generalized estimating equations with logit link function and working independence correlation structure. Results 18F FACBC tumor uptake was rapid but reversible. It peaked 3.6 minutes after injection and reached a relative plateau at 15–20 minutes (SUVmax[15–20min]). Mean prostate tumor SUVmax(15–20min) was significantly higher than that of the normal prostate (4.5 ± 0.5 vs 2.7 ± 0.5) (P < .001); however, it was not significantly different from that of BPH (4.3 ± 0.6) (P = .27). Sector-based comparison with histopathologic analysis, including all tumors, revealed sensitivity and specificity of 67% and 66%, respectively, for 18F FACBC PET/CT and 73% and 79%, respectively, for T2-weighted MR imaging. 18F FACBC PET/CT and MP MR

  16. Adaptive Radiotherapy for Prostate Cancer Using Kilovoltage Cone-Beam Computed Tomography: First Clinical Results

    SciTech Connect

    Nijkamp, Jasper; Pos, Floris J. Nuver, Tonnis T.; Jong, Rianne de; Remeijer, Peter; Sonke, Jan-Jakob; Lebesque, Joos V.

    2008-01-01

    Purpose: To evaluate the first clinical results of an off-line adaptive radiotherapy (ART) protocol for prostate cancer using kilovoltage cone-beam computed tomography (CBCT) in combination with a diet and mild laxatives. Methods and Materials: Twenty-three patients began treatment with a planning target volume (PTV) margin of 10 mm. The CBCT scans acquired during the first six fractions were used to generate an average prostate clinical target volume (AV-CTV), and average rectum (AV-Rect). Using these structures, a new treatment plan was generated with a 7-mm PTV margin. Weekly CBCT scans were used to monitor the CTV coverage. A diet and mild laxatives were introduced to improve image quality and reduce prostate motion. Results: Twenty patients were treated with conform ART protocol. For these patients, 91% of the CBCT scans could be used to calculate the AV-CTV and AV-Rect. In 96% of the follow-up CBCT scans, the CTV was located within the average PTV. In the remaining 4%, the prostate extended the PTV by a maximum of 1 mm. Systematic and random errors for organ motion were reduced by a factor of two compared with historical data without diet and laxatives. An average PTV reduction of 29% was achieved. The volume of the AV-Rect that received >65 Gy was reduced by 19%. The mean dose to the anal wall was reduced on average by 4.8 Gy. Conclusions: We safely reduced the high-dose region by 29%. The reduction in irradiated volume led to a significant reduction in the dose to the rectum. The diet and laxatives improved the image quality and tended to reduce prostate motion.

  17. Evaluation of T2-weighted and dynamic contrast-enhanced MRI in localizing prostate cancer before repeat biopsy.

    PubMed

    Cheikh, Alexandre Ben; Girouin, Nicolas; Colombel, Marc; Maréchal, Jean-Marie; Gelet, Albert; Bissery, Alvine; Rabilloud, Muriel; Lyonnet, Denis; Rouvière, Olivier

    2009-03-01

    We assessed the accuracy of T2-weighted (T2w) and dynamic contrast-enhanced (DCE) 1.5-T magnetic resonance imaging (MRI) in localizing prostate cancer before transrectal ultrasound-guided repeat biopsy. Ninety-three patients with abnormal PSA level and negative prostate biopsy underwent T2w and DCE prostate MRI using pelvic coil before repeat biopsy. T2w and DCE images were interpreted using visual criteria only. MR results were correlated with repeat biopsy findings in ten prostate sectors. Repeat biopsy found prostate cancer in 23 patients (24.7%) and 44 sectors (6.6%). At per patient analysis, the sensitivity, specificity, positive and negative predictive values were 47.8%, 44.3%, 20.4% and 79.5% for T2w imaging and 82.6%, 20%, 24.4% and 93.3% for DCE imaging. When all suspicious areas (on T2w or DCE imaging) were taken into account, a sensitivity of 82.6% and a negative predictive value of 100% could be achieved. At per sector analysis, DCE imaging was significantly less specific (83.5% vs. 89.7%, p < 0.002) than T2w imaging; it was more sensitive (52.4% vs. 32.1%), but the difference was hardly significant (p = 0.09). T2w and DCE MRI using pelvic coil and visual diagnostic criteria can guide prostate repeat biopsy, with a good sensitivity and NPV.

  18. Voxel-based population analysis for correlating local dose and rectal toxicity in prostate cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Acosta, Oscar; Drean, Gael; Ospina, Juan D.; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; de Crevoisier, Renaud

    2013-04-01

    The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (⩾Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80 Gy to the prostate by intensity modulated radiation therapy (IMRT). Within the patients presenting bleeding, a significant dose excess (6 Gy on average, p < 0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1 cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step.

  19. Intraoperative Radiotherapy During Radical Prostatectomy for Locally Advanced Prostate Cancer: Technical and Dosimetric Aspects

    SciTech Connect

    Krengli, Marco; Terrone, Carlo; Ballare, Andrea; Loi, Gianfranco; Tarabuzzi, Roberto; Marchioro, Giansilvio; Beldi, Debora; Mones, Eleonora; Bolchini, Cesare R.T.; Volpe, Alessandro; Frea, Bruno

    2010-03-15

    Purpose: To analyze the feasibility of intraoperative radiotherapy (IORT) in patients with high-risk prostate cancer and candidates for radical prostatectomy. Methods and Materials: A total of 38 patients with locally advanced prostate cancer were enrolled. No patients had evidence of lymph node or distant metastases, probability of organ-confined disease >25%, or risk of lymph node involvement >15% according to the Memorial Sloan-Kettering Cancer Center Nomogram. The IORT was delivered after exposure of the prostate by a dedicated linear accelerator with beveled collimators using electrons of 9 to 12 MeV to a total dose of 10-12 Gy. Rectal dose was measured in vivo by radiochromic films placed on a rectal probe. Administration of IORT was followed by completion of radical prostatectomy and regional lymph node dissection. All cases with extracapsular extension and/or positive margins were scheduled for postoperative radiotherapy. Patients with pT3 to pT4 disease or positive nodes received adjuvant hormonal therapy. Results: Mean dose detected by radiochromic films was 3.9 Gy (range, 0.4-8.9 Gy) to the anterior rectal wall. The IORT procedure lasted 31 min on average (range, 15-45 min). No major intra- or postoperative complications occurred. Minor complications were observed in 10/33 (30%) of cases. Of the 27/31 patients who completed the postoperative external beam radiotherapy, 3/27 experienced Grade 2 rectal toxicity and 1/27 experienced Grade 2 urinary toxicity. Conclusions: Use of IORT during radical prostatectomy is feasible and allows safe delivery of postoperative external beam radiotherapy to the tumor bed without relevant acute rectal toxicity.

  20. CYP17 inhibitors in prostate cancer: latest evidence and clinical potential.

    PubMed

    Alex, Anitha B; Pal, Sumanta K; Agarwal, Neeraj

    2016-07-01

    Since androgen signaling plays a pivotal role in the proliferation and metastasis of prostate cancer, androgen deprivation therapy (ADT) or castration therapy is considered the backbone of treatment for newly diagnosed metastatic prostate cancer. However, almost all men experience disease progression on ADT to a state known as metastatic castration-resistant prostate cancer (mCRPC), which continues to be driven by intratumoral androgen synthesis or androgen receptor signaling. Hence, the extragonadal ablation of androgen synthesis from pregnane precursors holds much promise. An inhibitor of cytochrome P450 17α-hydroxy/17,20-lyase (CYP17) enzymes, abiraterone acetate, has already been approved for men with mCRPC. Newer CYP17 inhibitors continue to be developed which are either more selective or have concomitant inhibitory actions on AR signaling. These include VT-464, orteronel, and galeterone. Herein, we focus on the molecular mechanism of action, efficacy, latest evidence, and clinical potential of CYP17 inhibitors in prostate cancer. PMID:27482286

  1. System for interstitial photodynamic therapy with online dosimetry: first clinical experiences of prostate cancer

    NASA Astrophysics Data System (ADS)

    Swartling, Johannes; Axelsson, Johan; Ahlgren, Göran; Kälkner, Karl Mikael; Nilsson, Sten; Svanberg, Sune; Svanberg, Katarina; Andersson-Engels, Stefan

    2010-09-01

    The first results from a clinical study for Temoporfin-mediated photodynamic therapy (PDT) of low-grade (T1c) primary prostate cancer using online dosimetry are presented. Dosimetric feedback in real time was applied, for the first time to our knowledge, in interstitial photodynamic therapy. The dosimetry software IDOSE provided dose plans, including optical fiber positions and light doses based on 3-D tissue models generated from ultrasound images. Tissue optical property measurements were obtained using the same fibers used for light delivery. Measurements were taken before, during, and after the treatment session. On the basis of these real-time measured optical properties, the light-dose plan was recalculated. The aim of the treatment was to ablate the entire prostate while minimizing exposure to surrounding organs. The results indicate that online dosimetry based on real-time tissue optical property measurements enabled the light dose to be adapted and optimized. However, histopathological analysis of tissue biopsies taken six months post-PDT treatment showed there were still residual viable cancer cells present in the prostate tissue sections. The authors propose that the incomplete treatment of the prostate tissue could be due to a too low light threshold dose, which was set to 5 J/cm2.

  2. The clinical efficacy and tolerability of doxazosin standard and gastrointestinal therapeutic system for benign prostatic hyperplasia.

    PubMed

    Fitzpatrick, John M; Desgrandchamps, François

    2005-03-01

    The therapeutic goal of treating benign prostatic hyperplasia (BPH) through early detection and effective therapy is to relieve the symptoms, improve patients' quality of life, decrease postvoid residual urine volume, and prevent the associated morbidity when the condition remains untreated. Alpha1-adrenoreceptor antagonists, e.g. doxazosin, terazosin, tamsulosin and alfuzosin, relax the bladder outlet to improve urinary flow, by reducing prostatic smooth muscle tone through the blockade of sympathetic adrenergic receptors. Doxazosin gastrointestinal therapeutic system (GITS) is a controlled-release formulation developed to enhance the pharmacokinetic profile of the drug while simultaneously minimizing possible adverse effects and reducing the need for dose titration. While both doxazosin standard and GITS are indicated for hypertension, they are also useful in the pharmacologically or naturally normotensive patient with BPH. In a cross-over trial comparing doxazosin GITS and tamsulosin, doxazosin gave a significantly greater improvement from baseline in symptoms. Results from recent trials (e.g. Medical Therapy of Prostatic Symptoms, MTOPS) showed that doxazosin was significantly more effective than the 5alpha-reductase inhibitor finasteride in relieving lower urinary tract symptoms, irrespective of prostate volume. The MTOPS trial showed clearly that over the long term, the combination of doxazosin and finasteride was more effective than either agent alone in significantly improving symptoms and reducing the clinical progression of BPH. Both doxazosin standard and GITS are well-tolerated, long-term therapies that are equally effective in younger and older men, and not associated with causing sexual dysfunction.

  3. CYP17 inhibitors in prostate cancer: latest evidence and clinical potential

    PubMed Central

    Alex, Anitha B.; Pal, Sumanta K.; Agarwal, Neeraj

    2016-01-01

    Since androgen signaling plays a pivotal role in the proliferation and metastasis of prostate cancer, androgen deprivation therapy (ADT) or castration therapy is considered the backbone of treatment for newly diagnosed metastatic prostate cancer. However, almost all men experience disease progression on ADT to a state known as metastatic castration-resistant prostate cancer (mCRPC), which continues to be driven by intratumoral androgen synthesis or androgen receptor signaling. Hence, the extragonadal ablation of androgen synthesis from pregnane precursors holds much promise. An inhibitor of cytochrome P450 17α−hydroxy/17,20-lyase (CYP17) enzymes, abiraterone acetate, has already been approved for men with mCRPC. Newer CYP17 inhibitors continue to be developed which are either more selective or have concomitant inhibitory actions on AR signaling. These include VT-464, orteronel, and galeterone. Herein, we focus on the molecular mechanism of action, efficacy, latest evidence, and clinical potential of CYP17 inhibitors in prostate cancer. PMID:27482286

  4. African American Participation in Oncology Clinical Trials--Focus on Prostate Cancer: Implications, Barriers, and Potential Solutions.

    PubMed

    Ahaghotu, Chiledum; Tyler, Robert; Sartor, Oliver

    2016-04-01

    In the United States, the incidence and mortality rates of many cancers, especially prostate cancer, are disproportionately high among African American men compared with Caucasian men. Recently, mortality rates for prostate cancer have declined more rapidly in African American versus Caucasian men, but prostate cancer is still the most common cancer and the second leading cause of cancer deaths in African American men in the United States. Compared with Caucasian men, prostate cancer occurs at younger ages, has a higher stage at diagnosis, and is more likely to progress after definitive treatments in African American men. Reasons for racial discrepancies in cancer are multifactorial and potentially include socioeconomic, cultural, nutritional, and biologic elements. In addition to improving access to novel therapies, clinical trial participation is essential to adequately establish the risks and benefits of treatments in African American populations. Considering the disproportionately high mortality rates noted in these groups, our understanding of the natural history and responses to therapies is limited. This review will explore African American underrepresentation in clinical trials with a focus on prostate cancer, and potentially effective strategies to engage African American communities in prostate cancer research. Solutions targeting physicians, investigators, the community, and health care systems are identified. Improvement of African American participation in prostate cancer clinical trials will benefit all stakeholders. PMID:26786562

  5. Prostate on the menu: an overview of cooking techniques and clinical outcome

    NASA Astrophysics Data System (ADS)

    van Swol, Christiaan F. P.; Verdaasdonck, Rudolf M.; van Venrooij, Ger E. P. M.; Boon, Tom A.

    1997-06-01

    In the past years there has been a significant increase in the treatment of bladder outlet obstruction caused by benign prostatic hyperplasia. Transurethral electroresection of the abundant tissue (TURP) has since the early seventies been the golden standard. The main drawback of a TURP is the relative lack of hemostasis, due to a confined energy and heat distribution around the resection loop. As sufficient tissue needs to be removed to overcome the bladder outlet obstruction, the ideal treatment has to combine both ablative and hemostatic abilities. After 1992, endoscopic laser and 'non laser' treatment modalities have been introduced, that competed with TURP as to clinical outcome. These treatments have in common that a high amounts of energy is delivered to the prostate to remove tissue either indirectly by coagulation necrosis or directly by vaporization. Various in-vitro and clinical studies were performed using different energy sources, such as Nd:YAG and diode laser light in combination with a large variety of delivery devices. Also TURP was included in the evaluation. The in-vitro results provided understanding of the efficiency in energy delivery, the extent of heat induced in the prostatic tissue and possible side-effects, using thermal imaging techniques. Over the last five years clinical data have been collected for various techniques with a follow-up of two years showing the contact techniques to be superior over non-contact and comparable with the outcome of the 'standard' TURP.

  6. Phase I trial of motexafin-lutetium-mediated interstitial photodynamic therapy in patients with locally recurrent prostate cancer

    NASA Astrophysics Data System (ADS)

    Stripp, Diana C. H.; Mick, Rosemarie; Zhu, Timothy C.; Whittington, Richard; Smith, Debbie; Dimofte, Andreea; Finlay, Jarod C.; Miles, Jeremy; Busch, Theresa M.; Shin, Daniel; Kachur, Alex; Tochner, Zelig A.; Malkowicz, S. Bruce; Glatstein, Eli; Hahn, Stephen M.

    2004-06-01

    Therapeutic options for patients with locally recurrent prostate cancer after treatment with radiation therapy are limited. An ongoing Phase I trial of interstitial photodynamic therapy (PDT) with the photosensitizer motexafin lutetium (MLu) was initiated in year 2000 for men with locally recurrent prostate cancer. The primary objective of this trial is to determine the maximally tolerated dose of motexafin lutetium-mediated PDT. Twelve men with biopsy-proven recurrent prostate cancer and no evidence of distant metastatic disease have been enrolled. Pre-treatment evaluation included an MRI of the prostate, bone scan, laboratory studies, cystoscopy, and transrectal ultrasound. Treatment plans were generated based upon the ultrasound findings. PDT dose was escalated by increasing the motexafin lutetium dose, increasing the 732 nm light dose, and decreasing the drug-light interval. Motexafin lutetium doses ranged from 0.5 to 2 mg/kg administered IV 3, 6, or 24 hours prior to 732 nm light delivery. The light dose measured in real time with in situ spherical detectors was 25-100 J/cm2 for all patients. Light was delivered through optical fibers inserted through a transperineal brachytherapy template in the operating room and optical property measurements were made before and after light therapy. Prostate biopsies were obtained before and after light delivery for spectrofluorometric measurements of photosensitizer uptake. Twelve patients have completed protocol treatment on eight dose levels without dose-limiting toxicity. Grade I PDT-related genitourinary symptoms were observed. One patient had Grade II urinary urgency that was urinary catheter-related. No rectal or other GI PDT-related toxicities were observed. Measurements of motexafin lutetium in prostate tissue demonstrated the presence of photosensitizer at all dose levels. Conclusions: Motexafin lutetium-mediated PDT designed to treat comprehensively the entired prostate gland has been well-tolerated at the doses

  7. Gene expression in normal-appearing tissue adjacent to prostate cancers are predictive of clinical outcome: evidence for a biologically meaningful field effect

    PubMed Central

    Magi-Galluzzi, Cristina; Maddala, Tara; Falzarano, Sara Moscovita; Cherbavaz, Diana B.; Zhang, Nan; Knezevic, Dejan; Febbo, Phillip G.; Lee, Mark; Lawrence, Hugh Jeffrey; Klein, Eric A.

    2016-01-01

    Purpose We evaluated gene expression in histologically normal-appearing tissue (NT) adjacent to prostate tumor in radical prostatectomy specimens, assessing for biological significance based on prediction of clinical recurrence (cR - metastatic disease or local recurrence). Results A total of 410 evaluable patients had paired tumor and NT. Fortysix genes, representing diverse biological pathways (androgen signaling, stromal response, stress response, cellular organization, proliferation, cell adhesion, and chromatin remodeling) were associated with cR in NT (FDR < 20%), of which 39 concordantly predicted cR in tumor (FDR < 20%). Overall GPS and its stromal response and androgen-signaling gene group components also significantly predicted time to cR in NT (RM-corrected HR/20 units = 1.25; 95% CI: 1.01-1.56; P = 0.024). Experimental Design Expression of 732 genes was measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) separately in tumor and adjacent NT specimens from 127 patients with and 374 without cR following radical prostatectomy for T1/T2 prostate cancer. A 17-gene expression signature (Genomic Prostate Score [GPS]), previously validated to predict aggressive prostate cancer when measured in tumor tissue, was also assessed using pre-specified genes and algorithms. Analysis used Cox proportional hazards models, Storey's false discovery rate (FDR) control, and regression to the mean (RM) correction. Conclusions Gene expression profiles, including GPS, from NT adjacent to tumor can predict prostate cancer outcome. These findings suggest that there is a biologically significant field effect in primary prostate cancer that is a marker for aggressive disease. PMID:27121323

  8. Evaluation of Image-Guidance Strategies in the Treatment of Localized Prostate Cancer

    SciTech Connect

    Kupelian, Patrick A. Lee, Choonik; Langen, Katja M.; Zeidan, Omar A.; Manon, Rafael R.; Willoughby, Twyla R.; Meeks, Sanford L.

    2008-03-15

    Purpose: To compare different image-guidance strategies in the alignment of prostate cancer patients. Using data from patients treated using daily image guidance, the remaining setup errors for several different strategies were retrospectively calculated. Methods and Materials: The alignment data from 74 patients treated with helical tomotherapy were analyzed, resulting in a data set of 2,252 fractions during which a megavoltage computed tomography image was used for image guidance with intraprostatic metallic fiducials. Given the daily positional adjustments, a variety of protocols, differing in imaging frequency and method, were retrospectively studied. The residual setup errors were determined for each protocol. Results: As expected, the systematic errors were effectively reduced with imaging. However, the random errors were unaffected. Even when image guidance was performed every other day with a running mean of the previous displacements, residual setup errors >5 mm occurred in 24% of all fractions. This frequency increased to about 40% if setup errors >3 mm were scored. Conclusion: Setup errors increased with decreasing frequency of image guidance. However, residual errors were still significant at the 5-mm level, even with imaging was performed every other day. This suggests that localizations must be performed daily in the set up of prostate cancer patients during a course of external beam radiotherapy.

  9. Is "Active Surveillance" an Acceptable Alternative?: A Qualitative Study of Couples' Decision Making about Early-Stage, Localized Prostate Cancer.

    PubMed

    Le, Chi L; McFall, Stephanie L; Byrd, Theresa L; Volk, Robert J; Cantor, Scott B; Kuban, Deborah A; Mullen, Patricia Dolan

    2016-01-01

    The objective of our study was to describe decision making by men and their partners regarding active surveillance (AS) or treatment for early-stage, localized prostate cancer. Fifteen couples were recruited from a cancer center multispecialty clinic, which gave full information about all options, including AS. Data were collected via individual, semi-structured telephone interviews. Most patients were white, non-Hispanic, had private insurance, had completed at least some college, and were aged 49-72 years. Ten chose AS. All partners were female, and couples reported strong marital satisfaction and cohesion. All couples described similar sequences of a highly emotional initial reaction and desire to be rid of the cancer, information seeking, and decision making. The choice of AS was built on a nuanced evaluation of the man's condition in which the couple differentiated prostate cancer from other cancers and early stage from later stages, wanted to avoid/delay side effects, and trusted the AS protocol to identify negative changes in time for successful treatment. Treated couples continued to want immediate treatment to remove the cancer. We concluded that having a partner's support for AS may help a man feel more comfortable with choosing and adhering to AS. Using decision aids that address both a man's and his partner's concerns regarding AS may increase its acceptability. Our research shows that some patients want to and do involve their partners in the decision-making process. Ethical issues are related to the tension between desire for partner involvement and the importance of the patient as autonomous decision-maker. The extended period of decision making, particularly for AS, is also an ethical issue that requires additional support for patients and couples in the making of fully informed choices that includes AS. PMID:27346824

  10. Is "Active Surveillance" an Acceptable Alternative?: A Qualitative Study of Couples' Decision Making about Early-Stage, Localized Prostate Cancer.

    PubMed

    Le, Chi L; McFall, Stephanie L; Byrd, Theresa L; Volk, Robert J; Cantor, Scott B; Kuban, Deborah A; Mullen, Patricia Dolan

    2016-01-01

    The objective of our study was to describe decision making by men and their partners regarding active surveillance (AS) or treatment for early-stage, localized prostate cancer. Fifteen couples were recruited from a cancer center multispecialty clinic, which gave full information about all options, including AS. Data were collected via individual, semi-structured telephone interviews. Most patients were white, non-Hispanic, had private insurance, had completed at least some college, and were aged 49-72 years. Ten chose AS. All partners were female, and couples reported strong marital satisfaction and cohesion. All couples described similar sequences of a highly emotional initial reaction and desire to be rid of the cancer, information seeking, and decision making. The choice of AS was built on a nuanced evaluation of the man's condition in which the couple differentiated prostate cancer from other cancers and early stage from later stages, wanted to avoid/delay side effects, and trusted the AS protocol to identify negative changes in time for successful treatment. Treated couples continued to want immediate treatment to remove the cancer. We concluded that having a partner's support for AS may help a man feel more comfortable with choosing and adhering to AS. Using decision aids that address both a man's and his partner's concerns regarding AS may increase its acceptability. Our research shows that some patients want to and do involve their partners in the decision-making process. Ethical issues are related to the tension between desire for partner involvement and the importance of the patient as autonomous decision-maker. The extended period of decision making, particularly for AS, is also an ethical issue that requires additional support for patients and couples in the making of fully informed choices that includes AS.

  11. A Phase II Trial of Arc-Based Hypofractionated Intensity-Modulated Radiotherapy in Localized Prostate Cancer

    SciTech Connect

    Lock, Michael; Best, Lara; Wong, Eugene; Bauman, Glenn; D'Souza, David; Venkatesan, Varagur; Sexton, Tracy; Ahmad, Belal; Izawa, Jonathan; Rodrigues, George

    2011-08-01

    Purpose: To evaluate acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and biochemical control of hypofractionated, image-guided (fiducial markers or ultrasound guidance), simplified intensity-modulated arc therapy for localized prostate cancer. Methods and Materials: This Phase II prospective clinical trial for T1a-2cNXM0 prostate cancer enrolled 66 patients who received 63.2 Gy in 20 fractions over 4 weeks. Fiducial markers were used for image guidance in 30 patients and daily ultrasound for the remainder. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: Median follow-up was 36 months. Acute Phase Grade 2 and 3 toxicity was 34% and 9% for GU vs. 25% and 10% for GI symptoms. One Grade 4 acute GI toxicity occurred in a patient with unrecognized Crohn's disease. Late Grade 2 and 3 toxicity for GU was 14% and 5%, and GI toxicity was 25% and 3%. One late GI Grade 4 toxicity was observed in a patient with significant comorbidities (anticoagulation, vascular disease). Acute GI toxicity {>=}Grade 2 was shown to be a predictor for late toxicity Grade {>=}2 (p < 0.001). The biochemical disease-free survival at 3 years was 95%. Conclusions: Hypofractionated simplified intensity-modulated arc therapy radiotherapy given as 63.2 Gy in 20 fractions demonstrated promising biochemical control rates; however, higher rates of acute Grade 3 GU and GI toxicity and higher late Grade 2 GU and GI toxicity were noted. Ongoing randomized controlled trials should ultimately clarify issues regarding patient selection and the true rate of severe toxicity that can be directly attributed to hypofractionated radiotherapy.

  12. Low-complexity atlas-based prostate segmentation by combining global, regional, and local metrics

    SciTech Connect

    Xie, Qiuliang; Ruan, Dan

    2014-04-15

    Purpose: To improve the efficiency of atlas-based segmentation without compromising accuracy, and to demonstrate the validity of the proposed method on MRI-based prostate segmentation application. Methods: Accurate and efficient automatic structure segmentation is an important task in medical image processing. Atlas-based methods, as the state-of-the-art, provide good segmentation at the cost of a large number of computationally intensive nonrigid registrations, for anatomical sites/structures that are subject to deformation. In this study, the authors propose to utilize a combination of global, regional, and local metrics to improve the accuracy yet significantly reduce the number of required nonrigid registrations. The authors first perform an affine registration to minimize the global mean squared error (gMSE) to coarsely align each atlas image to the target. Subsequently, atarget-specific regional MSE (rMSE), demonstrated to be a good surrogate for dice similarity coefficient (DSC), is used to select a relevant subset from the training atlas. Only within this subset are nonrigid registrations performed between the training images and the target image, to minimize a weighted combination of gMSE and rMSE. Finally, structure labels are propagated from the selected training samples to the target via the estimated deformation fields, and label fusion is performed based on a weighted combination of rMSE and local MSE (lMSE) discrepancy, with proper total-variation-based spatial regularization. Results: The proposed method was applied to a public database of 30 prostate MR images with expert-segmented structures. The authors’ method, utilizing only eight nonrigid registrations, achieved a performance with a median/mean DSC of over 0.87/0.86, outperforming the state-of-the-art full-fledged atlas-based segmentation approach of which the median/mean DSC was 0.84/0.82 when applying to their data set. Conclusions: The proposed method requires a fixed number of nonrigid

  13. Prostate biopsy

    MedlinePlus

    ... prostate biopsy; Fine needle biopsy of the prostate; Core biopsy of the prostate; Targeted prostate biopsy; Prostate biopsy - transrectal ultrasound (TRUS); Stereotactic transperineal prostate biopsy (STPB)

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

    SciTech Connect

    Genebes, Caroline; Filleron, Thomas; Graff, Pierre; Jonca, Frédéric; Huyghe, Eric; Thoulouzan, Matthieu; Soulie, Michel; Malavaud, Bernard; Aziza, Richard; Brun, Thomas; Delannes, Martine; Bachaud, Jean-Marc

    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-risk 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.

  15. Simultaneous integrated boost plan comparison of volumetric-modulated arc therapy and sliding window intensity-modulated radiotherapy for whole pelvis irradiation of locally advanced prostate cancer.

    PubMed

    Riou, Olivier; Regnault de la Mothe, Pauline; Azria, David; Aillères, Norbert; Dubois, Jean-Bernard; Fenoglietto, Pascal

    2013-07-08

    Concurrent radiotherapy to the pelvis plus a prostate boost with long-term androgen deprivation is a standard of care for locally advanced prostate cancer. IMRT has the ability to deliver highly conformal dose to the target while lowering irradiation of critical organs around the prostate. Volumetric-modulated arc therapy is able to reduce treatment time, but its impact on organ sparing is still controversial when compared to static gantry IMRT. We compared the two techniques in simultaneous integrated boost plans. Ten patients with locally advanced prostate cancer were included. The planning target volume (PTV) 1 was defined as the pelvic lymph nodes, the prostate, and the seminal vesicles plus setup margins. The PTV2 consisted of the prostate with setup margins. The prescribed doses to PTV1 and PTV2 were 54 Gy in 37 fractions and 74 Gy in 37 fractions, respectively. We compared simultaneous integrated boost plans by means of either a seven coplanar static split fields IMRT, or a one-arc (RA1) and a two-arc (RA2) RapidArc planning. All three techniques allowed acceptable homogeneity and PTV coverage. Static IMRT enabled a better homogeneity for PTV2 than RapidArc techniques. Sliding window IMRT and VMAT permitted to maintain doses to OAR within acceptable levels with a low risk of side effects for each organ. VMAT plans resulted in a clinically and statistically significant reduction in doses to bladder (mean dose IMRT: 50.1 ± 4.6Gy vs. mean dose RA2: 47.1 ± 3.9 Gy, p = 0.037), rectum (mean dose IMRT: 44± 4.5 vs. mean dose RA2: 41.6 ± 5.5 Gy, p = 0.006), and small bowel (V30 IMRT: 76.47 ± 14.91% vs. V30 RA2: 47.49 ± 16.91%, p = 0.002). Doses to femoral heads were higher with VMAT but within accepted constraints. Our findings suggest that simultaneous integrated boost plans using VMAT and sliding window IMRT allow good OAR sparing while maintaining PTV coverage within acceptable levels.

  16. Establishment of a New Prostate Cancer Multidisciplinary Clinic: Format and Initial Experience

    PubMed Central

    Sundi, Debasish; Cohen, Jason E; Cole, Alexander P; Neuman, Brian P; Cooper, John; Faisal, Farzana A; Ross, Ashley E; Schaeffer, Edward M

    2014-01-01

    Background The use of multidisciplinary clinics (MDCs) for outpatient cancer evaluation is increasing. MDCs may vary in format, and data on whether MDCs change prostate cancer (PCa) care are limited. Here we report on the setup and design of a relatively new PCa MDC clinic. Because MDC evaluation was associated with a comprehensive re-evaluation of all patients' staging and risk stratification data, we studied the frequency of changes in PCa grade and stage upon MDC evaluation, which provides a unique estimate of the magnitude of pathology, radiology, and exam-based risk stratification in a modern tertiary setting. Methods In 2008–2012, 887 patients underwent consultation for newly diagnosed PCa at the Johns Hopkins Hospital (JHH) weekly MDC. In a same-day process, patients are interviewed and examined in a morning clinic. Examination findings, radiology studies, and biopsy slides are then reviewed during a noon conference that involves real-time collaboration among JHH attending specialty physicians: urologists, radiation oncologists, medical oncologists, pathologists, and radiologists. During afternoon consultations, attending physicians appropriate to each patients' eligible treatment options individually meet with patients to discuss management strategies and/or clinical trials. Retrospective chart review identified presenting tumor characteristics based on outside assessment, which was compared with stage and grade as determined at MDC evaluation. Results Overall, 186/647 (28.7%) had a change in their risk category or stage. For example, 2.9% of men were down-classified as very-low-risk, rendering them eligible for active surveillance. 5.7% of men thought to have localized cancer were up-classified as metastatic, thus prompting systemic management approaches. Using NCCN guidelines as a benchmark, many men were found to have undergone nonindicated imaging (bone scan 23.9%, CT/MRI 47.4%). The three most chosen treatments after MDC evaluation were external beam

  17. Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer.

    PubMed

    Yang, Ruijie; Zhao, Nan; Liao, Anyan; Wang, Hao; Qu, Ang

    2016-01-01

    To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D90 of 34Gy in 8.5Gy per fraction, and 145Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2Gy per fraction, EQD2) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The Dmean (EQD2) of rectum decreased 22.36Gy in HDR and 17.01Gy in LDR from 30.24Gy in VMAT, respectively. The Dmean (EQD2) of bladder decreased 6.91Gy in HDR and 2.53Gy in LDR from 13.46Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD2) was 80.26, 70.23, and 104.91Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR.

  18. Saudi oncology society and Saudi urology association combined clinical management guidelines for prostate cancer.

    PubMed

    Abusamra, Ashraf; Murshid, Esam; Kushi, Hussain; Alkhateeb, Sultan; Al-Mansour, Mubarak; Saadeddin, Ahmad; Rabah, Danny; Bazarbashi, Shouki; Alotaibi, Mohammed; Alghamdi, Abdullah; Alghamdi, Khalid; Alsharm, Abdullah; Ahmad, Imran

    2016-01-01

    This is an update to the previously published Saudi guidelines for the evaluation, medical, and surgical management of patients diagnosed with prostate cancer. It is categorized according to the stage of the disease using the tumor node metastasis staging system 7(th) edition. The guidelines are presented with supporting evidence level, they are based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi oncology society and Saudi urological association. Considerations to the local availability of drugs, technology, and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health care policy makers in the management of patients diagnosed with adenocarcinoma of the prostate to. PMID:27141178

  19. Saudi oncology society and Saudi urology association combined clinical management guidelines for prostate cancer

    PubMed Central

    Abusamra, Ashraf; Murshid, Esam; Kushi, Hussain; Alkhateeb, Sultan; Al-Mansour, Mubarak; Saadeddin, Ahmad; Rabah, Danny; Bazarbashi, Shouki; Alotaibi, Mohammed; Alghamdi, Abdullah; Alghamdi, Khalid; Alsharm, Abdullah; Ahmad, Imran

    2016-01-01

    This is an update to the previously published Saudi guidelines for the evaluation, medical, and surgical management of patients diagnosed with prostate cancer. It is categorized according to the stage of the disease using the tumor node metastasis staging system 7th edition. The guidelines are presented with supporting evidence level, they are based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi oncology society and Saudi urological association. Considerations to the local availability of drugs, technology, and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health care policy makers in the management of patients diagnosed with adenocarcinoma of the prostate to. PMID:27141178

  20. DWI of Prostate Cancer: Optimal b-Value in Clinical Practice

    PubMed Central

    Manenti, Guglielmo; Vasili, Erald; Bonanno, Elena; Simonetti, Giovanni

    2014-01-01

    Aim. To compare the diagnostic performance of diffusion weighted imaging (DWI) using b-values of 1000 s/mm2 and 2000 s/mm2 at 3 Tesla (T) for the evaluation of clinically significant prostate cancer. Matherials and Methods. Seventy-eight prostate cancer patients underwent a 3T MRI scan followed by radical prostatectomy. DWI was performed using b-values of 0, 1000, and 2000 s/mm2 and qualitatively analysed by two radiologists. ADC maps were obtained at b-values of 1000 and 2000 s/mm2 and quantitatively analyzed in consensus. Results. For diagnosis of 78 prostate cancers the accuracy of DWI for the young reader was significantly greater at b = 2000 s/mm2 for the peripheral zone (PZ) but not for the transitional zone (TZ). For the experienced reader, DWI did not show significant differences in accuracy between b-values of 1000 and 2000 s/mm2. The quantitative analysis in the PZ and TZ was substantially superimposable between the two b-values, albeit with a higher accuracy with a b-value of 2000 s/mm2. Conclusions. With a b-value of 2000 s/mm2 at 3T both readers differentiated clinical significant cancer from benign tissue; higher b-values can be helpful for the less experienced readers. PMID:24693438

  1. Management of Localized Prostate Cancer by Focal Transurethral Resection of Prostate Cancer: An Application of Radical TUR-PCa to Focal Therapy

    PubMed Central

    Morita, Masaru; Matsuura, Takeshi

    2012-01-01

    Background. We analyzed radical TUR-PCa against localized prostate cancer. Patients and Methods. Seventy-nine out of 209 patients with prostate cancer in one lobe were studied. Patients' age ranged from 58 to 91 years and preoperative PSA, 0.70 to 17.30 ng/mL. In other 16 additional patients we performed focal TUR-PCa. Patients' age ranged from 51 to 87 years and preoperative PSA, 1.51 to 25.74 ng/mL. Results. PSA failure in radical TUR-PCa was 5.1% during the mean follow-up period of 58.9 months. The actuarial biochemical non-recurrence rate was 98.2% for pT2a and 90.5% for pT2b. Bladder neck contracture occurred in 28 patients (35.4%). In 209 patients, pathological study revealed prostate cancer of the peripheral zone near the neurovascular bundle bilaterally in 25%, unilaterally in 39% and no cancer bilaterally in 35%, suggesting the possibility of focal TUR-PCa. Postoperative PSA of 16 patients treated by focal TUR-PCa was stable between 0.007 and 0.406 ng/mL at 24.2 months' follow-up. No patients suffered from urinary incontinence. Bladder neck contracture developed in only 1 patient and all 5 patients underwent nerve-preserving TUR-PCa did not show erectile dysfunction. Conclusion. Focal TUR-PCa was considered to be a promising option among focal therapies against localized prostate cancer. PMID:22675347

  2. Photoacoustic imaging of prostate brachytherapy seeds in ex vivo prostate

    NASA Astrophysics Data System (ADS)

    Kuo, Nathanael; Kang, Hyun Jae; DeJournett, Travis; Spicer, James; Boctor, Emad

    2011-03-01

    The localization of brachytherapy seeds in relation to the prostate is a key step in intraoperative treatment planning (ITP) for improving outcomes in prostate cancer patients treated with low dose rate prostate brachytherapy. Transrectal ultrasound (TRUS) has traditionally been the modality of choice to guide the prostate brachytherapy procedure due to its relatively low cost and apparent ease of use. However, TRUS is unable to visualize seeds well, precluding ITP and producing suboptimal results. While other modalities such as X-ray and magnetic resonance imaging have been investigated to localize seeds in relation to the prostate, photoacoustic imaging has become an emerging and promising modality to solve this challenge. Moreover, photoacoustic imaging may be more practical in the clinical setting compared to other methods since it adds little additional equipment to the ultrasound system already adopted in procedure today, reducing cost and simplifying engineering steps. In this paper, we demonstrate the latest efforts of localizing prostate brachytherapy seeds using photoacoustic imaging, including visualization of multiple seeds in actual prostate tissue. Although there are still several challenges to be met before photoacoustic imaging can be used in the operating room, we are pleased to present the current progress in this effort.

  3. Combining radiation therapy and androgen deprivation for localized prostate cancer—a critical review

    PubMed Central

    Dal Pra, A.; Cury, F.L.; Souhami, L.

    2010-01-01

    Interest has been increasing in the use of androgen deprivation therapy (adt) combined with radiation therapy (rt) in the management of localized prostate cancer. Preclinical studies have provided some rationale for the use of this combination. In patients with high-risk disease, the benefit of a combined approach, with the addition of adjuvant hormonal therapy, is supported by results of randomized trials. In contrast, for patients with low-risk disease, there is no obvious therapeutic advantage except for cytoreduction. The usefulness of short-term hormonal therapy in association with rt for intermediate-risk patients is still debatable, particularly in the context of dose-escalated rt. The optimal timing and duration of adt, in the neoadjuvant and adjuvant settings alike, are still under investigation. In view of the potential side effects with adt, further studies are being performed to better identify subsets of patients who will definitely benefit from this therapy in combination with rt. PMID:20975876

  4. Small cell carcinoma of the prostate

    PubMed Central

    Nadal, Rosa; Schweizer, Michael; Kryvenko, Oleksandr N.; Epstein, Jonathan I.; Eisenberger, Mario A.

    2015-01-01

    Pure small-cell carcinoma (SCC) of the prostate is a rare entity and one of the most aggressive malignancies of the prostate. Histologically, prostatic SCCs of the prostate are part of a spectrum of anaplastic tumours of the prostate and are similar to SCCs of the lungs. In most cases, SCC of the prostate is associated with conventional prostatic adenocarcinoma. Both components of these mixed tumours frequently share molecular alterations such as ERG gene rearrangements or AURKA and MYCN amplifications, suggesting a common clonal origin. The clinical behaviour of small-cell prostate carcinomas is characterized by extensive local disease, visceral disease, and low PSA levels despite large metastatic burden. Commonly, the emergence of the SCC occurs in patients with high-grade adenocarcinoma who are often treated with androgen deprivation treatment (ADT). However, SCCs do not usually benefit from ADT. A biopsy of accessible lesions is strongly recommended to identify those with SCC pathological features, as management is undoubtedly affected by this finding. Chemotherapy is the standard approach for treating patients with either localized or advanced prostatic SCC. Despite the emergence of more-aggressive treatment modalities, the prognosis of men with prostatic SCC remains dismal. PMID:24535589

  5. Towards Clinically Optimized MRI-guided Surgical Manipulator for Minimally Invasive Prostate Percutaneous Interventions: Constructive Design*

    PubMed Central

    Eslami, Sohrab; Fischer, Gregory S.; Song, Sang-Eun; Tokuda, Junichi; Hata, Nobuhiko; Tempany, Clare M.; Iordachita, Iulian

    2013-01-01

    This paper undertakes the modular design and development of a minimally invasive surgical manipulator for MRI-guided transperineal prostate interventions. Severe constraints for the MRI-compatibility to hold the minimum artifact on the image quality and dimensions restraint of the bore scanner shadow the design procedure. Regarding the constructive design, the manipulator kinematics has been optimized and the effective analytical needle workspace is developed and followed by proposing the workflow for the manual needle insertion. A study of the finite element analysis is established and utilized to improve the mechanism weaknesses under some inevitable external forces to ensure the minimum structure deformation. The procedure for attaching a sterile plastic drape on the robot manipulator is discussed. The introduced robotic manipulator herein is aimed for the clinically prostate biopsy and brachytherapy applications. PMID:24683502

  6. MRI-compatible transurethral ultrasound system for the treatment of localized prostate cancer using rotational control.

    PubMed

    Chopra, Rajiv; Baker, Nicole; Choy, Vanessa; Boyes, Aaron; Tang, Kee; Bradwell, David; Bronskill, Michael J

    2008-04-01

    Magnetic resonance imaging (MRI)-guided transurethral ultrasound therapy is a potential minimally invasive treatment for localized prostate cancer offering precise targeting of tissue within the gland, short treatment times, and the capability to quantify the spatial heating pattern delivered during therapy. A significant challenge in MRI-guided ultrasound therapy is the design and construction of MRI-compatible equipment capable of operation in a closed-bore MR imager. We describe a prototype system developed for MRI-guided transurethral ultrasound therapy and characterize the performance of the different components including the heating applicator design, rotational motor, and radio frequency electronics. The ultrasound heating applicator described in this study incorporates a planar transducer and is capable of producing high intensity ultrasound energy in a localized region of tissue. Results demonstrated that the heating applicator exhibits excellent MRI-compatibility, enabling precise MR temperature measurements to be acquired as close as 6 mm from the device. Simultaneous imaging and rotational motion was also possible during treatment using a motor based on piezoelectric actuators. Heating experiments performed in both phantoms and in a canine model with the prototype system verified the capability to perform simultaneous MR imaging and therapy delivery with this system. Real-time control over therapy using MR temperature measurements acquired during heating can be implemented to achieve precise patterns of thermal damage within the prostate gland. The technical feasibility of using the system developed in this study for MRI-guided transurethral ultrasound therapy in a closed-bore MR imager has been demonstrated. PMID:18491529

  7. Phase II Trial of Hypofractionated Image-Guided Intensity-Modulated Radiotherapy for Localized Prostate Adenocarcinoma

    SciTech Connect

    Martin, Jarad M.; Rosewall, Tara; Bayley, Andrew; Bristow, Robert; Chung, Peter; Crook, Juanita; Gospodarowicz, Mary; McLean, Michael; Menard, Cynthia; Milosevic, Michael; Warde, Padraig; Catton, Charles

    2007-11-15

    Purpose: To assess in a prospective trial the feasibility and late toxicity of hypofractionated radiotherapy (RT) for prostate cancer. Methods and Materials: Eligible patients had clinical stage T1c-2cNXM0 disease. They received 60 Gy in 20 fractions over 4 weeks with intensity-modulated radiotherapy including daily on-line image guidance with intraprostatic fiducial markers. Results: Between June 2001 and March 2004, 92 patients were treated with hypofractionated RT. The cohort had a median prostate-specific antigen value of 7.06 ng/mL. The majority had Gleason grade 5-6 (38%) or 7 (59%) disease, and 82 patients had T1c-T2a clinical staging. Overall, 29 patients had low-risk, 56 intermediate-risk, and 7 high-risk disease. Severe acute toxicity (Grade 3-4) was rare, occurring in only 1 patient. Median follow-up was 38 months. According to the Phoenix definition for biochemical failure, the rate of biochemical control at 14 months was 97%. According to the previous American Society for Therapeutic Radiology and Oncology definition, biochemical control at 3 years was 76%. The incidence of late toxicity was low, with no severe (Grade {>=}3) toxicity at the most recent assessment. Conclusions: Hypofractionated RT using 60 Gy in 20 fractions over 4 weeks with image guidance is feasible and is associated with low rates of late bladder and rectal toxicity. At early follow-up, biochemical outcome is comparable to that reported for conventionally fractionated controls. The findings are being tested in an ongoing, multicenter, Phase III trial.

  8. Opioid requirement, opioid receptor expression, and clinical outcomes in patients with advanced prostate cancer

    PubMed Central

    Zylla, Dylan; Gourley, Brett L.; Vang, Derek; Jackson, Scott; Boatman, Sonja; Lindgren, Bruce; Kuskowski, Michael A.; Le, Chap; Gupta, Kalpna; Gupta, Pankaj

    2013-01-01

    Background Preclinical studies show that opioids stimulate angiogenesis and tumor progression through the mu opioid receptor (MOR). Although MOR is over-expressed in several human malignancies, the effect of chronic opioid requirement on cancer progression or survival has not been examined in humans. Methods We performed a retrospective analysis on 113 patients identified in the Minneapolis VA Tumor Registry (test cohort) and 480 patients from the national VA Central Cancer Registry (validation cohort) diagnosed with stage IV prostate cancer between 1995 and 2010, to examine whether MOR expression or opioid requirement is associated with disease progression and survival. All opioids were converted to oral morphine equivalents (OME) for comparison. Laser scanning confocal microscopy was used to analyze MOR-immunoreactivity in prostate cancer biopsies. The effects of variables on outcomes were analyzed in univariable and multivariable models. Results In patients with metastatic prostate cancer, MOR expression and opioid requirement were independently associated with inferior progression-free survival (PFS) (HR 1.65, 1.33–2.07; p<0.001 and HR 1.08, 1.03–1.13; p<0.001, respectively) and overall survival (OS; HR 1.55, 1.20–1.99; p<0.001 and HR 1.05, 1.00–1.10; p=0.031, respectively). The validation cohort confirmed that increasing opioid requirement was associated with worse OS (HR 1.005, 1.002–1.008, p=0.001). Conclusion Higher MOR expression and greater opioid requirement are associated with shorter PFS and OS in patients with metastatic prostate cancer. Nevertheless, clinical practice should not be changed until prospective randomized trials show that opioid use is associated with inferior clinical outcomes, and that abrogation of the peripheral activities of opioids ameliorates this effect. PMID:24104703

  9. Advantages of caudal block over intrarectal local anesthesia plus periprostatic nerve block for transrectal ultrasound guided prostate biopsy

    PubMed Central

    Wang, Na; Fu, Yaowen; Ma, Haichun; Wang, Jinguo; Gao, Yang

    2016-01-01

    Objective: To compare caudal block with intrarectal local anesthesia plus periprostatic nerve block for transrectal ultrasound guided prostate biopsy. Methods: One hundred and ninety patients scheduled for transrectal ultrasound guided prostate biopsy were randomized equally into Group-A who received caudal block (20 ml 1.2% lidocaine) and Group-B who received intrarectal local anesthesia (0.3% oxybuprocaine cream) plus periprostatic nerve block (10 ml 1% lidocaine plus 0.5% ropivacaine) before biopsy. During and after the procedure, the patients rated the level of pain/discomfort at various time points. Complications during the whole study period and the patient overall satisfaction were also evaluated. Results: More pain and discomfort was detected during periprostatic nerve block than during caudal block. Pain and discomfort was significantly lower during prostate biopsy and during the manipulation of the probe in the rectum in Group-A than in Group-B. No significant differences were detected in the pain intensity after biopsy and side effects between the two groups. Conclusions: Caudal block provides better anesthesia than periprostatic nerve block plus intrarectal local anesthesia for TRUS guided prostate biopsy without an increase of side effects. PMID:27648052

  10. [Correction of local and central disorders in patients with chronic abacterial prostatitis in usage of amus-01-intramag unit].

    PubMed

    Glybochko, P V; Gol'braĭkh, G E; Raĭgorodskiĭ, Iu M; Valiev, A Z; Surikov, V N

    2007-01-01

    Combined use of dynamic magnetotherapy of local and central action in combination with antibacterial endourethral therapy and rectal administration of vitaprost arrests symptoms of chronic prostatitis. Combination of local and total dynamic magnetotherapy with application of AMUS-01-INTRAMAG unit improves erection quality in 81.8% males with psychogenic form of erectile dysfunction. There was also improvement of spermogram parameters and relieve of asthenovegetative syndrome. PMID:17915452

  11. 15-Year biochemical relapse free survival in clinical Stage T1-T3 prostate cancer following combined external beam radiotherapy and brachytherapy; Seattle experience

    SciTech Connect

    Sylvester, John E. . E-mail: johnsylvester@seattleprostate.com; Grimm, Peter D.; Blasko, John C.; Millar, Jeremy; Orio, Peter F.; Skoglund, Scott; Galbreath, Robert W.; Merrick, Gregory

    2007-01-01

    Purpose: Long-term biochemical relapse-free survival (BRFS) rates in patients with clinical Stages T1-T3 prostate cancer continue to be scrutinized after treatment with external beam radiation therapy and brachytherapy. Methods and Materials: We report 15-year BRFS rates on 223 patients with clinically localized prostate cancer that were consecutively treated with I{sup 125} or Pd {sup 103} brachytherapy after 45-Gy neoadjuvant EBRT. Multivariate regression analysis was used to create a pretreatment clinical prognostic risk model using a modified American Society for Therapeutic Radiology and Oncology consensus definition (two consecutive serum prostate-specific antigen rises) as the outcome. Gleason scoring was performed by the pathologists at a community hospital. Time to biochemical failure was calculated and compared by using Kaplan-Meier plots. Results: Fifteen-year BRFS for the entire treatment group was 74%. BRFS using the Memorial Sloan-Kettering risk cohort analysis (95% confidence interval): low risk, 88%, intermediate risk 80%, and high risk 53%. Grouping by the risk classification described by D'Amico, the BRFS was: low risk 85.8%, intermediate risk 80.3%, and high risk 67.8% (p = 0.002). Conclusions: I{sup 125} or Pd{sup 103} brachytherapy combined with supplemental EBRT results in excellent 15-year biochemical control. Different risk group classification schemes lead to different BRFS results in the high-risk group cohorts.

  12. Maximum vs. Mono Androgen Blockade and the Risk of Recurrence in Men With Localized Prostate Cancer Undergoing Brachytherapy

    SciTech Connect

    Chen, Ronald C. Sadetsky, Natalia; Chen, M.-H.; Carroll, Peter R.; D'Amico, Anthony V.

    2009-09-01

    Purpose: We examined whether maximum androgen blockade (MAB) is associated with a decreased recurrence risk vs. single-agent androgen suppression (monotherapy) for men undergoing brachytherapy (BT) for localized prostate cancer. Methods and Materials: Data from 223 men in Cancer of the Prostate Strategic Urologic Research Endeavor database who received androgen deprivation therapy (ADT) concurrent with BT for intermediate- or high-risk prostatic adenocarcinoma were included; 159 (71%) received MAB, and 64 (29%) monotherapy (luteinizing hormone-releasing hormone agonist or anti-androgen alone). Cox regression analysis was performed to assess whether the choice of ADT was associated with disease recurrence adjusting for known prognostic factors. Results: Men who received MAB had similar Gleason scores, T categories, and pretreatment prostate-specific antigen as those who received monotherapy. After a median follow-up of 49 months, the use of MAB was not associated with a decrease in the risk recurrence (p = 0.72), after adjusting for known prognostic factors. A higher PSA at diagnosis (p = 0.03) and younger age at diagnosis (p < 0.01) were associated with increased recurrence risk. The 3-year recurrence free survival was 76% for patients in both monotherapy and MAB groups. Conclusions: There are varied practice patterns in physicians' choice of the extent of concurrent ADT when used with brachytherapy for men with intermediate- or high-risk prostate cancer. Given a lack of demonstrated superiority from either ADT choice, both appear to be reasonable options.

  13. Enhancing the effectiveness of androgen deprivation in prostate cancer by inducing Filamin A nuclear localization

    PubMed Central

    Mooso, Benjamin A.; Vinall, Ruth L.; Tepper, Clifford G.; Savoy, Rosalinda M.; Cheung, Jean P.; Singh, Sheetal; Siddiqui, Salma; Wang, Yu; Bedolla, Roble G.; Martinez, Anthony; Mudryj, Maria; Kung, Hsing-Jien; deVere White, Ralph W.; Ghosh, Paramita M.

    2013-01-01

    Since prostate cancer (CaP) is regulated by androgen receptor (AR) activity, metastatic CaP is treated with androgen deprivation therapy (ADT). Despite initial response, patients on ADT eventually progress to castration-resistant CaP (CRPC), which is currently incurable. We previously showed that cleavage of the 280kDa structural protein Filamin A (FlnA) to a 90kDa fragment, and nuclear localization of the cleaved product, sensitized CRPC cells to ADT. Hence, treatment promoting FlnA nuclear localization would enhance androgen responsiveness. Here, we show that FlnA nuclear localization induced apoptosis in CRPC cells during ADT, identifying it as a treatment tool in advanced CaP. Significantly, the natural product genistein-combined-polysaccharide (GCP) had a similar effect. Investigation of the mechanism of GCP-induced apoptosis showed that GCP induced FlnA cleavage and nuclear localization, and that apoptosis resulting from GCP treatment was mediated by FlnA nuclear localization. Two main components of GCP are genistein and daidzein: the ability of GCP to induce G2 arrest was due to genistein whereas sensitivity to ADT stemmed from daidzein; hence both were needed to mediate GCP's effects. FlnA cleavage is regulated by its phosphorylation; we show that ADT enhanced FlnA phosphorylation, which prevented its cleavage, whereas GCP inhibited FlnA phosphorylation, thereby sensitizing CaP cells to ADT. In a mouse model of CaP recurrence, GCP, but not vehicle, impeded relapse following castration; indicating that GCP, when administered with ADT, interrupted the development of CRPC. These results demonstrate the efficacy of GCP in promoting FlnA nuclear localization and enhancing androgen responsiveness in CaP. PMID:22993077

  14. Screening for Prostate Cancer

    MedlinePlus

    ... of Internal Medicine Summaries for Patients Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee ... Physicians The full report is titled “Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee ...

  15. Advantages and limitations of navigation-based multicriteria optimization (MCO) for localized prostate cancer IMRT planning

    SciTech Connect

    McGarry, Conor K.; Bokrantz, Rasmus; O’Sullivan, Joe M.; Hounsell, Alan R.

    2014-10-01

    Efficacy of inverse planning is becoming increasingly important for advanced radiotherapy techniques. This study’s aims were to validate multicriteria optimization (MCO) in RayStation (v2.4, RaySearch Laboratories, Sweden) against standard intensity-modulated radiation therapy (IMRT) optimization in Oncentra (v4.1, Nucletron BV, the Netherlands) and characterize dose differences due to conversion of navigated MCO plans into deliverable multileaf collimator apertures. Step-and-shoot IMRT plans were created for 10 patients with localized prostate cancer using both standard optimization and MCO. Acceptable standard IMRT plans with minimal average rectal dose were chosen for comparison with deliverable MCO plans. The trade-off was, for the MCO plans, managed through a user interface that permits continuous navigation between fluence-based plans. Navigated MCO plans were made deliverable at incremental steps along a trajectory between maximal target homogeneity and maximal rectal sparing. Dosimetric differences between navigated and deliverable MCO plans were also quantified. MCO plans, chosen as acceptable under navigated and deliverable conditions resulted in similar rectal sparing compared with standard optimization (33.7 ± 1.8 Gy vs 35.5 ± 4.2 Gy, p = 0.117). The dose differences between navigated and deliverable MCO plans increased as higher priority was placed on rectal avoidance. If the best possible deliverable MCO was chosen, a significant reduction in rectal dose was observed in comparison with standard optimization (30.6 ± 1.4 Gy vs 35.5 ± 4.2 Gy, p = 0.047). Improvements were, however, to some extent, at the expense of less conformal dose distributions, which resulted in significantly higher doses to the bladder for 2 of the 3 tolerance levels. In conclusion, similar IMRT plans can be created for patients with prostate cancer using MCO compared with standard optimization. Limitations exist within MCO regarding conversion of navigated plans to

  16. mp-MRI Prostate Characterised PIRADS 3 Lesions are Associated with a Low Risk of Clinically Significant Prostate Cancer - A Retrospective Review of 92 Biopsied PIRADS 3 Lesions

    PubMed Central

    Liddell, Heath; Jyoti, Rajeev; Haxhimolla, Hodo Z.

    2015-01-01

    Objective To determine whether prostate image reporting and data system (PIRADS) 3 lesions as assessed by a 3T multiparametric magnetic resonance imaging (MRI) represent clinically significant prostate cancer. Method A retrospective review was performed on a series of consecutive patients who underwent MRI guided biopsy of the prostate for clinical suspicion of prostate cancer between January 2013 and March 2014. Demographic, clinical, MRI and biopsy data were reviewed and compared. The same 3T MRI without the use of an endo-rectal coil was employed to assess each patient, obtaining high resolution T2 weighted images, diffusion weighted imaging and dynamic contrast enhancement. The MRI data was sent to Dynacad software for analysis. A single experienced radiologist reported all the studies from this series using a modified PIRADS scoring system. Subsequently, all the lesions marked PIRADS 3 or above were targeted with 18G core biopsy using DynaTrim in-gantry MRI guidance system. Needle position targeting the lesion was recorded prior to each biopsy. All core biopsy samples were sent to one of two pathology laboratories where they were processed and reported as per the International Society of Urological Pathology protocols. Results One hundred and eighteen patients comprising a total of 215 lesions were reviewed. Amongst this cohort, 92 PIRADS 3 lesions were identified and biopsied. The mean age of patients in this cohort was 62.6 years. Median prostate specific antigen (PSA) was 6.5 ng/ml and median prostate size was 78.4 ml. Eightysix (93.5%) of biopsied PIRADS 3 lesions were benign and 6 (6.5%) lesions were found to be malignant. Of these 6 malignant lesions, 4 (66%) were Gleason score 6 (3 + 3) and 2 (33%) were Gleason score 7 (3 + 4). Of the 86 non-malignant lesions, 1 (1.2%) represented high-grade prostate intraepithelial neoplasia and 2 (2.4%) represented atypical small acinar proliferation. PIRADS 3 lesions within the peripheral zone were more likely to be

  17. Health-Related Quality of Life After Stereotactic Body Radiation Therapy for Localized Prostate Cancer: Results From a Multi-institutional Consortium of Prospective Trials

    SciTech Connect

    King, Christopher R.; Collins, Sean; Fuller, Donald; Wang, Pin-Chieh; Kupelian, Patrick; Steinberg, Michael; Katz, Alan

    2013-12-01

    Purpose: To evaluate the early and late health-related quality of life (QOL) outcomes among prostate cancer patients following stereotactic body radiation therapy (SBRT). Methods and Materials: Patient self-reported QOL was prospectively measured among 864 patients from phase 2 clinical trials of SBRT for localized prostate cancer. Data from the Expanded Prostate Cancer Index Composite (EPIC) instrument were obtained at baseline and at regular intervals up to 6 years. SBRT delivered a median dose of 36.25 Gy in 4 or 5 fractions. A short course of androgen deprivation therapy was given to 14% of patients. Results: Median follow-up was 3 years and 194 patients remained evaluable at 5 years. A transient decline in the urinary and bowel domains was observed within the first 3 months after SBRT which returned to baseline status or better within 6 months and remained so beyond 5 years. The same pattern was observed among patients with good versus poor baseline function and was independent of the degree of early toxicities. Sexual QOL decline was predominantly observed within the first 9 months, a pattern not altered by the use of androgen deprivation therapy or patient age. Conclusion: Long-term outcome demonstrates that prostate SBRT is well tolerated and has little lasting impact on health-related QOL. A transient and modest decline in urinary and bowel QOL during the first few months after SBRT quickly recovers to baseline levels. With a large number of patients evaluable up to 5 years following SBRT, it is unlikely that unexpected late adverse effects will manifest themselves.

  18. Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer

    PubMed Central

    Du, Meijun; Dittmar, Rachel L.; Lee, Adam; Nandy, Debashis; Yuan, Tiezheng; Guo, Yongchen; Wang, Yuan; Tschannen, Michael R.; Worthey, Elizabeth; Jacob, Howard; See, William; Kilari, Deepak; Wang, Xuexia; Hovey, Raymond L.; Huang, Chiang-Ching; Wang, Liang

    2015-01-01

    Liquid biopsies, examinations of tumor components in body fluids, have shown promise for predicting clinical outcomes. To evaluate tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall survival, we applied whole genome and targeted sequencing to examine the plasma cfDNAs derived from 20 patients with advanced prostate cancer. Sequencing-based genomic abnormality analysis revealed locus-specific gains or losses that were common in prostate cancer, such as 8q gains, AR amplifications, PTEN losses and TMPRSS2-ERG fusions. To estimate tumor burden in cfDNA, we developed a Plasma Genomic Abnormality (PGA) score by summing the most significant copy number variations. Cox regression analysis showed that PGA scores were significantly associated with overall survival (p < 0.04). After androgen deprivation therapy or chemotherapy, targeted sequencing showed significant mutational profile changes in genes involved in androgen biosynthesis, AR activation, DNA repair, and chemotherapy resistance. These changes may reflect the dynamic evolution of heterozygous tumor populations in response to these treatments. These results strongly support the feasibility of using non-invasive liquid biopsies as potential tools to study biological mechanisms underlying therapy-specific resistance and to predict disease progression in advanced prostate cancer. PMID:25915538

  19. Prostate Localization on Daily Cone-Beam Computed Tomography Images: Accuracy Assessment of Similarity Metrics

    SciTech Connect

    Kim, Jinkoo; Hammoud, Rabih; Pradhan, Deepak; Zhong Hualiang; Jin, Ryan Y.; Movsas, Benjamin; Chetty, Indrin J.

    2010-07-15

    Purpose: To evaluate different similarity metrics (SM) using natural calcifications and observation-based measures to determine the most accurate prostate and seminal vesicle localization on daily cone-beam CT (CBCT) images. Methods and Materials: CBCT images of 29 patients were retrospectively analyzed; 14 patients with prostate calcifications (calcification data set) and 15 patients without calcifications (no-calcification data set). Three groups of test registrations were performed. Test 1: 70 CT/CBCT pairs from calcification dataset were registered using 17 SMs (6,580 registrations) and compared using the calcification mismatch error as an endpoint. Test 2: Using the four best SMs from Test 1, 75 CT/CBCT pairs in the no-calcification data set were registered (300 registrations). Accuracy of contour overlays was ranked visually. Test 3: For the best SM from Tests 1 and 2, accuracy was estimated using 356 CT/CBCT registrations. Additionally, target expansion margins were investigated for generating registration regions of interest. Results: Test 1-Incremental sign correlation (ISC), gradient correlation (GC), gradient difference (GD), and normalized cross correlation (NCC) showed the smallest errors ({mu} {+-} {sigma}: 1.6 {+-} 0.9 {approx} 2.9 {+-} 2.1 mm). Test 2-Two of the three reviewers ranked GC higher. Test 3-Using GC, 96% of registrations showed <3-mm error when calcifications were filtered. Errors were left/right: 0.1 {+-} 0.5mm, anterior/posterior: 0.8 {+-} 1.0mm, and superior/inferior: 0.5 {+-} 1.1 mm. The existence of calcifications increased the success rate to 97%. Expansion margins of 4-10 mm were equally successful. Conclusion: Gradient-based SMs were most accurate. Estimated error was found to be <3 mm (1.1 mm SD) in 96% of the registrations. Results suggest that the contour expansion margin should be no less than 4 mm.

  20. Impact of hormonal treatment duration in combination with radiotherapy for locally advanced prostate cancer: Meta-analysis of randomized trials

    PubMed Central

    2010-01-01

    Background Hormone therapy plus radiotherapy significantly decreases recurrences and mortality of patients affected by locally advanced prostate cancer. In order to determine if difference exists according to the hormonal treatment duration, a literature-based meta-analysis was performed. Methods Relative risks (RR) were derived through a random-effect model. Differences in primary (biochemical failure, BF; cancer-specific survival, CSS), and secondary outcomes (overall survival, OS; local or distant recurrence, LR/DM) were explored. Absolute differences (AD) and the number needed to treat (NNT) were calculated. Heterogeneity, a meta-regression for clinic-pathological predictors and a correlation test for surrogates were conducted. Results Five trials (3,424 patients) were included. Patient population ranged from 267 to 1,521 patients. The longer hormonal treatment significantly improves BF (with significant heterogeneity) with an absolute benefit of 10.1%, and a non significant trend in CSS. With regard to secondary end-points, the longer hormonal treatment significantly decrease both the LR and the DM with an absolute difference of 11.7% and 11.5%. Any significant difference in OS was observed. None of the three identified clinico-pathological predictors (median PSA, range 9.5-20.35, Gleason score 7-10, 27-55% patients/trial, and T3-4, 13-77% patients/trial), did significantly affect outcomes. At the meta-regression analysis a significant correlation between the overall treatment benefit in BF, CSS, OS, LR and DM, and the length of the treatment was found (p≤0.03). Conclusions Although with significant heterogeneity (reflecting different patient' risk stratifications), a longer hormonal treatment duration significantly decreases biochemical, local and distant recurrences, with a trend for longer cancer specific survival. PMID:21143897

  1. Early voiding dysfunction associated with prostate brachytherapy.

    PubMed

    Wagner; Nag; Young; Bahnson

    2000-12-15

    Introduction: Transperineal prostate brachytherapy is gaining popularity as a treatment for clinically localized carcinoma of the prostate. Very little prospective data exists addressing the issue of complications associated with this procedure. We present an analysis of the early voiding dysfunction associated with prostate brachytherapy. Materials and Methods: Forty-six consecutive patients who underwent Palladium-103 (Pd-103) seed placement for clinically localized prostate carcinoma were evaluated prospectively for any morbidity associated with the procedure. Twenty-three patients completed an International Prostate Symptom Score (IPSS) questionnaire preoperatively, at their first postoperative visit, and at their second postoperative visit. The total IPSS, each of the seven individual components, and the "bother" score were evaluated separately for each visit, and statistical significance was determined. Results: Urinary retention occurred in 7/46 patients (15%). Of these, 5 were able to void spontaneously after catheter removal. One patient is maintained with a suprapubic tube, and one patient is currently on continuous intermittent catheterization. Baseline IPSS was 7.1 and this went to 20.0 at the first postoperative visit (p<0.001). By the second postoperative visit, the IPSS was 8.0. Conclusions: In our experience, prostate brachytherapy for localized carcinoma of the prostate is associated with a 15% catheterization rate and a significant increase in the IPSS (7.1 to 20.0). This increase in the IPSS seems to be self-limited. Patients need to be educated on these issues prior to prostate brachytherapy. PMID:11113369

  2. Daily Isocenter Correction With Electromagnetic-Based Localization Improves Target Coverage and Rectal Sparing During Prostate Radiotherapy

    SciTech Connect

    Rajendran, Ramji Ramaswamy; Plastaras, John P.; Mick, Rosemarie; McMichael Kohler, Diane; Kassaee, Alireza; Vapiwala, Neha

    2010-03-15

    Purpose: To evaluate dosimetric consequences of daily isocenter correction during prostate cancer radiation therapy using the Calypso 4D localization system. Methods and Materials: Data were analyzed from 28 patients with electromagnetic transponders implanted in their prostates for daily target localization and tracking. Treatment planning isocenters were recorded based on the values of the vertical, longitudinal, and lateral axes. Isocenter location obtained via alignment with skin tattoos was compared with that obtained via the electromagnetic localization system. Daily isocenter shifts, based on the isocenter location differences between the two alignment methods in each spatial axis, were calculated for each patient over their entire course. The mean isocenter shifts were used to determine dosimetric consequences of treatment based on skin tattoo alignments alone. Results: The mean += SD of the percentages of treatment days with shifts beyond += 0.5 cm for vertical, longitudinal and lateral shifts were 62% += 28%, 35% += 26%, and 38% +=21%, respectively. If daily electromagnetic localization was not used, the excess in prescribed dose delivered to 70% of the rectum was 10 Gy and the deficit in prescribed dose delivered to 95% of the planning target volume was 10 Gy. The mean isocenter shift was not associated with the volumes of the prostate, rectum, or bladder, or with patient body mass index. Conclusions: Daily isocenter localization can reduce the treatment dose to the rectum. Correcting for this variability could lead to improved dose delivery, reduced side effects, and potentially improved treatment outcomes.

  3. Longitudinal Effects of Social Support and Adaptive Coping on the Emotional Well-Being of Survivors of Localized Prostate Cancer

    PubMed Central

    Zhou, Eric S.; Penedo, Frank J.; Bustillo, Natalie E.; Benedict, Catherine; Rasheed, Mikal; Lechner, Suzanne; Soloway, Mark; Kava, Bruce R.; Schneiderman, Neil; Antoni, Michael H.

    2010-01-01

    Survivors of prostate cancer experience treatment-related physical side effects that can compromise emotional well-being for years post treatment. There is limited research investigating how social support and the use of coping may affect the emotional well-being of this population following treatment. The aim of this study was to investigate how social support and coping impact emotional well-being 2 years after treatment in survivors of localized prostate cancer who have received either radical prostatectomy or radiotherapy. Psychosocial and disease-specific measures were administered to an ethnically and demographically diverse sample of 180 men treated for localized prostate cancer at baseline and at 2-year follow-up. Regression analyses demonstrated that higher levels of social support at baseline predicted better emotional well-being 2 years later. Furthermore, higher levels of adaptive coping at baseline partially mediated the relationship between social support and emotional well-being. Supportive relationships may contribute to improved emotional well-being following treatment by facilitating the use of adaptive coping strategies. Attention should be given to strengthening social support networks and educating survivors of prostate cancer on adaptive coping techniques. PMID:21086876

  4. THE IMPORTANCE OF LOCAL CONTROL IN EARLY STAGE PROSTATE CANCER: OUTCOMES OF PATIENTS WITH A POSITIVE POST-RADIOTHERAPY BIOPSY TREATED ON RTOG 9408

    PubMed Central

    Krauss, Daniel J.; Hu, Chen; Bahary, Jean-Paul; Souhami, Luis; Gore, Elizabeth M.; Chafe, Susan Maria Jacinta; Leibenhaut, Mark H.; Narayan, Samir; Torres-Roca, Javier; Michalski, Jeff; Zeitzer, Kenneth L.; Donavanik, Viroon; Sandler, Howard; McGowan, David G.; Jones, Christopher U.; Shipley, William U.

    2015-01-01

    Purpose To assess the association of positive post-radiotherapy (RT) biopsy with subsequent clinical outcomes in men with localized prostate cancer. Methods RTOG 94-08 analyzed 1979 men with stage T1b-T2b, PSA ≤ 20 prostate cancer testing whether 4 months of total androgen suppression (TAS) added to RT improved survival over RT alone. Patients randomized to TAS received flutamide with leutenizing hormone releasing hormone (LHRH) agonist. Per protocol, patients without evidence of clinical recurrence or initiation of additional endocrine therapy underwent repeat prostate biopsy 2 years following RT completion. Statistical analysis was performed to evaluate the impact of positive post-RT biopsies on clinical outcomes. Results 831 patients underwent post-RT biopsy, 398 treated with RT alone and 433 RT + TAS. Patients with positive post-RT biopsies had higher rates of biochemical failure (BCF) [HR=1.7; 95% CI 1.3–2.1] and distant metastasis (DM) [HR=2.4; 95% CI 1.3–4.4] as well as inferior disease specific survival (DSS) [HR=3.8; 95% CI 1.9–7.5]. Positive biopsy remained predictive of such outcomes after correction for potential confounders such as Gleason score, tumor stage, and TAS administration. Prior TAS did not prevent elevated risk of adverse outcome in the setting of post-RT positive biopsy. Patients with Gleason score ≥ 7 with a positive biopsy additionally had inferior overall survival compared to those with a negative biopsy [HR=1.56; 95% CI 1.04–2.35]. Conclusions Positive post-RT biopsy is associated with increased rates of DM and inferior DSS in patients treated with definitive RT and was associated with inferior OS for patients with high-grade tumors. PMID:26104939

  5. Therapeutic efficacy and safety of photo-selective vaporization of prostate under local anaesthesia with light sedation

    NASA Astrophysics Data System (ADS)

    Arum, Carl-Jørgen; Romundstad, Paal; Mjønes, Jan

    2007-02-01

    OBJECTIVES: We evaluated the therapeutic efficacy and safety of photo-selective vaporization of the prostate (PVP) under local anaesthesia in patients suffering from lower urinary tract symptoms (LUTS) secondary to prostatic obstruction. MATERIAL & METHODS: 150 patients at the average age of 73 (range 51-92) and a mean/median ASA-score of 2.4/2.0 were included. PVP was performed under either general or spinal anaesthesia in the first 67 patients and under local anaesthesia (peri-prostatic infiltration with 0.25% bupivacain-adrenalin 20 ml) and light sedation in the remaining 83 patients. Surgical variables including asa-score, operative-time, blood-pressure, oxygen saturation, pre- and post-op haemoglobin (Hgb) were recorded. Post operative need for pain medication, catheter-time, and time to pts. hospital discharge were also recorded. RESULTS: No patient with local anaesthesia required conversion to general anaesthesia. The median Hgb fall from pre-op. to post-op. was 0.55g/dl. The median requirement for post-op. catheterization was 2 hrs after local anaesthesia and 9 hrs after general or spinal anaesthesia. The median time from operation to hospital discharge was 12 hrs in local anaesthesia and 24 hrs for general or spinal anaesthesia (p<0.001). At 12 and 18 months postoperatively, the following factors were significantly (p<0.001) improved: trans-rectal ultrasound, international prostate symptom score, quality of life score, post-void residual urine volume, flow max/average. At 12 months urodynamic studies revealed significant improvement (p<0.001) for opening pressure, pressure @ flow-max, micturation resistance and bladder outlet obstruction index. CONCLUSION: PVP under local anaesthesia and light sedation provides excellent intraoperative safety, expedient post operative recovery, significant symptom relief as well as improvement in uro-dynamic outcomes.

  6. Circulating Prostate Cells Found in Men with Benign Prostate Disease Are P504S Negative: Clinical Implications

    PubMed Central

    Murray, Nigel P.; Reyes, Eduardo; Badínez, Leonardo; Orellana, Nelson; Fuentealba, Cynthia; Olivares, Ruben; Porcell, José; Dueñas, Ricardo

    2013-01-01

    Introduction. Developments in immunological and quantitative real-time PCR-based analysis have enabled the detection, enumeration, and characterization of circulating tumor cells (CTCs). It is assumed that the detection of CTCs is associated with cancer, based on the finding that CTCs can be detected in all major cancer and not in healthy subjects or those with benign disease. Methods and Patients. Consecutive men, with suspicion of prostate cancer, had blood samples taken before prostate biopsy; mononuclear cells were obtained using differential gel centrifugation and CPCs detecting using anti-PSA immunocytochemistry. Positive samples underwent further classification with anti-P504S. Results. 329 men underwent prostate biopsy; of these men 83 underwent a second biopsy and 44 a third one. Of those with a biopsy negative for cancer, 19/226 (8.4%) had CPCs PSA (+) P504S (−) detected at first biopsy, 6/74 (8.1%) at second biopsy, and 5/33 (15.2%) at third biopsy. Men with cancer-positive biopsies did not have PSA (+) P504S (−) CPCs detected. These benign cells were associated with chronic prostatitis. Conclusions. Patients with chronic prostatitis may have circulating prostate cells detected in blood, which do not express the enzyme P504S and should be thought of as benign in nature. PMID:23690774

  7. The Evolving Biology of Castration-Resistant Prostate Cancer: Review of Recommendations From the Prostate Cancer Clinical Trials Working Group 3.

    PubMed

    Geethakumari, Praveen Ramakrishnan; Cookson, Michael S; Kelly, William Kevin

    2016-02-01

    In 2008, the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) developed consensus guidelines for clinical trial design and conduct that redefined trial endpoints, with a dual-objective paradigm: to (1) controlling, relieving, or eliminating disease manifestations at the start of treatment; and (2) preventing or delaying further disease manifestations. Clinical and translational research in prostate cancer has expanded our current-day understanding of the mechanisms of its pathogenesis, as well as the different clinicopathologic and molecular subtypes of the disease, and has improved the therapeutic armamentarium for the management of metastatic castration-resistant prostate cancer (CRPC). These new advances led to the development of the updated PCWG3 guidelines in 2015. In this review, we analyze our evolving understanding of the biology of CRPC, acquired resistance mechanisms, and emerging therapeutic targets in light of the updated PCWG3 guidelines. We present a joint perspective from the medical oncology and urologic disciplines on the ongoing efforts to advance clinical trial performance in order to discover new therapies for this fatal disease.

  8. Clinical nodal staging scores for prostate cancer: a proposal for preoperative risk assessment

    PubMed Central

    Kluth, L A; Abdollah, F; Xylinas, E; Rieken, M; Fajkovic, H; Seitz, C; Sun, M; Karakiewicz, P I; Schramek, P; Herman, M P; Becker, A; Hansen, J; Ehdaie, B; Loidl, W; Pummer, K; Lee, R K; Lotan, Y; Scherr, D S; Seiler, D; Ahyai, S A; Chun, F K-H; Graefen, M; Tewari, A; Nonis, A; Bachmann, A; Montorsi, F; Gönen, M; Briganti, A; Shariat, S F

    2014-01-01

    Background: Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status. Methods: We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes. Results: In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1–6 nodes in cT1 and 6–8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively. Conclusions: Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis. PMID:25003663

  9. Chronic prostatitis: management strategies.

    PubMed

    Murphy, Adam B; Macejko, Amanda; Taylor, Aisha; Nadler, Robert B

    2009-01-01

    The National Institutes of Health (NIH) has redefined prostatitis into four distinct entities. Category I is acute bacterial prostatitis. It is an acute prostatic infection with a uropathogen, often with systemic symptoms of fever, chills and hypotension. The treatment hinges on antimicrobials and drainage of the bladder because the inflamed prostate may block urinary flow. Category II prostatitis is called chronic bacterial prostatitis. It is characterized by recurrent episodes of documented urinary tract infections with the same uropathogen and causes pelvic pain, urinary symptoms and ejaculatory pain. It is diagnosed by means of localization cultures that are 90% accurate in localizing the source of recurrent infections within the lower urinary tract. Asymptomatic inflammatory prostatitis comprises NIH category IV. This entity is, by definition, asymptomatic and is often diagnosed incidentally during the evaluation of infertility or prostate cancer. The clinical significance of category IV prostatitis is unknown and it is often left untreated. Category III prostatitis is called chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). It is characterized by pelvic pain for more than 3 of the previous 6 months, urinary symptoms and painful ejaculation, without documented urinary tract infections from uropathogens. The syndrome can be devastating, affecting 10-15% of the male population, and results in nearly 2 million outpatient visits each year. The aetiology of CP/CPPS is poorly understood, but may be the result of an infectious or inflammatory initiator that results in neurological injury and eventually results in pelvic floor dysfunction in the form of increased pelvic muscle tone. The diagnosis relies on separating this entity from chronic bacterial prostatitis. If there is no history of documented urinary tract infections with a urinary tract pathogen, then cultures should be taken when patients are symptomatic. Prostatic localization cultures, called the

  10. Testing for the recurrent HOXB13 G84E germline mutation in men with clinical indications for prostate biopsy

    PubMed Central

    Schroeck, Florian R.; Zuhlke, Kimberly A.; Siddiqui, Javed; Siddiqui, Rabia; Cooney, Kathleen A.; Wei, John T.

    2014-01-01

    Purpose The G84E variant of HOXB13 was recently found to be associated with a significantly increased risk of prostate cancer in a case control study. We estimated the prevalence of this mutation in a clinical population of men at risk for prostate cancer scheduled to undergo prostate biopsy. Materials and Methods We prospectively collected clinical information and DNA samples from men undergoing diagnostic prostate biopsy between June 2005 and October 2011. We genotyped samples for HOXB13 G84E using the MassARRAY system. We determined the prevalence of the G84E variant in the overall cohort, among patients with positive family history (FH), and among men age 55 years or younger. Results 1175 subjects underwent biopsy, of which 948 had a DNA sample for analysis. Four patients had the G84E variant detected [prevalence 0.42%, 95% confidence interval (CI) 0.12% - 1.12%], of which three had prostate cancer on biopsy. None of 301 patients with a positive FH (prevalence 0.00%, 95% CI 0.00% – 1.52%) and one of 226 subjects age 55 years or younger tested positive (prevalence 0.44%, 95% CI 0.01% – 2.44%). Conclusion The HOXB13 G84E variant is rare in this cohort, even in those with a positive family history. Our findings question the utility of testing for this variant among unselected men presenting for a diagnostic prostate biopsy. PMID:23036981

  11. Loss of TIMP-1 immune expression and tumor recurrence in localized prostate cancer

    PubMed Central

    dos Reis, Sabrina Thalita; Viana, Nayara Izabel; Iscaife, Alexandre; Pontes, José; Dip, Nelson; Antunes, Alberto Azoubel; Guimarães, Vanessa Ribeiro; Santana, Isaque; Nahas, William Carlos; Srougi, Miguel; Leite, Katia Ramos Moreira

    2015-01-01

    ABSTRACT Introduction and objective: Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC). Materials and Methods: Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months. Results: The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases. Conclusion: Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression. PMID:26742965

  12. Polyunsaturated fatty acids affect the localization and signaling of PIP3/AKT in prostate cancer cells.

    PubMed

    Gu, Zhennan; Wu, Jiansheng; Wang, Shihua; Suburu, Janel; Chen, Haiqin; Thomas, Michael J; Shi, Lihong; Edwards, Iris J; Berquin, Isabelle M; Chen, Yong Q

    2013-09-01

    AKT is a serine-threonine protein kinase that plays important roles in cell growth, proliferation and apoptosis. It is activated after binding to phosphatidylinositol phosphates (PIPs) with phosphate groups at positions 3,4 and 3,4,5 on the inositol ring. In spite of extensive research on AKT, one aspect has been largely overlooked, namely the role of the fatty acid chains on PIPs. PIPs are phospholipids composed of a glycerol backbone with fatty acids at the sn-1 and sn-2 position and inositol at the sn-3 position. Here, we show that polyunsaturated fatty acids (PUFAs) modify phospholipid content. Docosahexaenoic acid (DHA), an ω3 PUFA, can replace the fatty acid at the sn-2 position of the glycerol backbone, thereby changing the species of phospholipids. DHA also inhibits AKT(T308) but not AKT(S473) phosphorylation, alters PI(3,4,5)P3 (PIP3) and phospho-AKT(S473) protein localization, decreases pPDPK1(S241)-AKT and AKT-BAD interaction and suppresses prostate tumor growth. Our study highlights a potential novel mechanism of cancer inhibition by ω3 PUFA through alteration of PIP3 and AKT localization and affecting the AKT signaling pathway.

  13. Mature Results of the Ottawa Phase II Study of Intermittent Androgen-Suppression Therapy in Prostate Cancer: Clinical Predictors of Outcome

    SciTech Connect

    Malone, Shawn . E-mail: smalone@ottawahospital.on.ca; Perry, Gad; Eapen, Libni; Segal, Roanne; Gallant, Victor; Dahrouge, Simone; Crook, Juanita; Spaans, Johanna N.

    2007-07-01

    Purpose: To present the mature experience of a phase II trial of intermittent androgen suppression (IAS). Methods and Materials: Intermittent androgen-suppression therapy was initiated in prostate-cancer patients to delay hormone resistance and minimize potential side effects of androgen-deprivation therapy (ADT). Patients received cyclical periods of ADT and observation (off-treatment interval [OTI]). Androgen-deprivation therapy was reinitiated when the level of prostate-specific antigen (PSA) rose above 10 ng/ml, or for disease progression. Associations between clinical factors and eligibility for OTI were measured. Kaplan-Meier and Cox regression analyses were used to determine factors predicting the duration of OTIs. Results: Ninety-five patients completed 187 cycles of treatment. The median duration of OTIs was 8.5 months. Patients with higher PSA and metastatic disease were less likely to be eligible for the first OTI (p < 0.01). In multivariate analysis, patients with higher PSA and local relapse had significantly longer OTIs (p < 0.01) compared with metastatic patients. The median time to withdrawal from the study was 37 months. Conclusions: Intermittent androgen suppression appears to be a favorable treatment option for patients with biochemically (according to level of PSA) or locally recurrent prostate cancer with favorable long-term survival, a high probability of eligibility for OTIs, and durable OTIs.

  14. Clinical and technical aspects of bipolar transurethral prostate resection.

    PubMed

    Faul, Peter; Schlenker, Boris; Gratzke, Christian; Stief, Christian G; Reich, Oliver; Hahn, Robert Gustaw

    2008-01-01

    This review aims to provide an overview and critical assessment of the developments in transurethral electroresection in non-conductive and conductive irrigants. In the 1970s, measurements of the electric pathway in saline were performed for different locations of the neutral electrode. It was then concluded that the current pathway and the possible hazards of burn injuries to the patient should be investigated separately for each arrangement of the neutral electrode. The position and shape of the neutral electrode have decisive effects on the current flow in the patient. Thus, different electrode arrangements of the various bipolar resection systems need to be analysed separately. Furthermore, not only electrical power, but also conductivity and quality of the lubricant gel have to be considered as critical factors with regard to electrothermal injuries of the urethra. The supposedly better cutting quality seems to be based more on subjective observations than on scientific valid data. When performing "bipolar" TUR it is necessary to consider all electrotechnical and clinical aspects, particularly with regard to the potential risk of thermoelectrical urethral damage. PMID:18622807

  15. Advanced image reconstruction strategies for 4D prostate DCE-MRI: steps toward clinical practicality

    NASA Astrophysics Data System (ADS)

    Stinson, Eric G.; Borisch, Eric A.; Froemming, Adam T.; Kawashima, Akira; Young, Phillip M.; Warndahl, Brent A.; Grimm, Roger C.; Manduca, Armando; Riederer, Stephen J.; Trzasko, Joshua D.

    2015-09-01

    Dynamic contrast-enhanced (DCE) MRI is an important tool for the detection and characterization of primary and recurring prostate cancer. Advanced reconstruction strategies (e.g., sparse or low-rank regression) provide improved depiction of contrast dynamics and pharmacokinetic parameters; however, the high computation cost of reconstructing 4D (3D+time, 50+ frames) datasets typically inhibits their routine clinical use. Here, a novel alternating direction method-of-multipliers (ADMM) optimization strategy is described that enables these methods to be executed in ∠5 minutes, and thus within the standard clinical workflow. After overviewing the mechanics of this approach, high-performance implementation strategies will be discussed and demonstrated through clinical cases.

  16. High-Intensity Focused Ultrasound for the Treatment of Localized and Locally Advanced Hormone-Resistant Prostate Cancer: 2,5 Year Outcome

    NASA Astrophysics Data System (ADS)

    Solovov, V. A.; Dvoynikov, S. Y.; Vozdvizhenskiy, M. O.

    2011-09-01

    Introduction & Objectives: High-Intensity Focused Ultrasound (HIFU) has been shown to be a successful treatment for localised prostate cancer (PC). Here we have explored the effectiveness of the HIFU treatment for hormone-resistant prostate cancer (HRPC). Materials & Methods: 341 patients were treated in our center between September 2007 and December 2009; all of them showed treatment failure following hormone ablation. The median time before hormone-resistance was 20 (3-48) months. In the group with localised PC: number of patients 237, Gleason score ≤7, stage T1-2N0M0, age 69 (60-89) years, mean PSA before treatment 40,0 (5,8-92,9) ng/ml, mean prostate volume—39,3 (28-92) cc; in the group with locally advanced PC: number of patients 104, Gleason score ≤9, stage T2-3N0M0, age 72 (52-83) years, PSA before treatment 30,3 (20,1-60) ng/ml, mean prostate volume—41,2 (25-198) cc. HIFU was delivered under spinal anesthesia using the Ablatherm HIFU device (EDAP, France). Pre HIFU transurethral resection of the prostate (TURP) was performed for all patients. Mean follow-up time 18 months (3-30). Results: The median PSA level 12 months after HIFU treatment was 0,04 (0-2,24) ng/ml—localised PC, and for locally advanced disease—0,05 (0-48,4) ng/ml, at 18 months after HIFU treatment this was 0,2 (0,02-2,0) ng/ml for localised PC, and for locally advanced disease 0,18 (0,04-7,45) ng/ml. Patients with localised PC has 4,5% recurrence, those with locally advanced PC 20%. Kaplan-Meir analyses of the total group indicated that the risk of recurrence after 1 year follow-up was 10%, the risk of recurrence was 19% after 2 years of follow-up. Conclusions: Our initial experience shows that ultrasound ablation is safe, minimally invasive and effective as a treatment for localised and locally advanced hormone-resistant prostate cancer.

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

    SciTech Connect

    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: 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.

  18. Long-Term Outcome and Toxicity of Salvage Brachytherapy for Local Failure After Initial Radiotherapy for Prostate Cancer

    SciTech Connect

    Burri, Ryan J.; Stone, Nelson N.; Unger, Pam; Stock, Richard G.

    2010-08-01

    Purpose: To describe long-term outcomes and toxicity after salvage brachytherapy (BT) for local failure after initial radiotherapy for prostate cancer. Methods and Materials: Between 1994 and 2008, 37 men with local failure after initial prostate radiotherapy (32 external-beam radiation therapy [EBRT] and 5 BT) underwent salvage BT with {sup 103}Pd or {sup 125}I. Estimates of freedom from biochemical failure (FFbF, Phoenix definition) and cause-specific survival (CSS) were calculated using the Kaplan-Meier method. Toxicities were graded using CTCv3.0. Results: Median follow-up was 86 months (range, 2-156). The median dose to 90% of the prostate volume was 122 Gy (range, 67-166). The 10-year FFbF and CSS were 54% and 96%, respectively. On univariate analysis, prostate-specific antigen (PSA) >10 ng/mL at initial diagnosis was significantly associated with FFbF (p = 0.01), and there were trends for both age <70 years (p = 0.08) and PSA <6 ng/mL (p = 0.08) at the time of salvage BT. On multivariate analysis, only presalvage PSA <6 ng/mL (p = 0.046) was significantly associated with improved FFbF. There were three Grade 3 toxicities and one Grade 4 toxicity. Pelvic lymph node dissection before salvage BT was the only variable significantly associated with Grade {>=}2 toxicity (p = 0.03). Conclusion: With a median follow-up of 86 months, salvage prostate BT was associated with a 10-year FFbF of 54% and CSS of 96%. Improved FFbF was associated with a presalvage PSA <6 ng/mL. Toxicity was worse in patients who had undergone pelvic lymph node dissection before salvage BT. Careful patient selection for salvage BT may result in improved outcomes and reduced toxicity.

  19. Sexual Function After Stereotactic Body Radiotherapy for Prostate Cancer: Results of a Prospective Clinical Trial

    SciTech Connect

    Wiegner, Ellen A.; King, Christopher R.

    2010-10-01

    Purpose: To study the sexual quality of life for prostate cancer patients after stereotactic body radiotherapy (SBRT). Methods and Materials: Using the Expanded Prostate Cancer Index Composite (EPIC)-validated quality-of-life questionnaire, the sexual function of 32 consecutive patients who received prostate SBRT in a prospective Phase II clinical trial were analyzed at baseline, and at median times of 4, 12, 20, and 50 months after treatment. SBRT consisted of 36.25 Gy in five fractions of 7.25 Gy using the Cyberknife. No androgen deprivation therapy was given. The use of erectile dysfunction (ED) medications was monitored. A comprehensive literature review for radiotherapy-alone modalities based on patient self-reported questionnaires served as historical comparison. Results: Median age at treatment was 67.5 years, and median follow-up was 35.5 months (minimum 12 months). The mean EPIC sexual domain summary score, sexual function score, and sexual bother score decreased by 45%, 49%, and 25% respectively at 50 months follow-up. These differences reached clinical relevance by 20 months after treatment. Baseline ED rate was 38% and increased to 71% after treatment (p = 0.024). Use of ED medications was 3% at baseline and progressed to 25%. For patients aged <70 years at follow-up, 60% maintained satisfactory erectile function after treatment compared with only 12% aged {>=}70 years (p = 0.008). Penile bulb dose was not associated with ED. Conclusions: The rates of ED after treatment appear comparable to those reported for other modalities of radiotherapy. Given the modest size of this study and the uncertainties in the physiology of radiotherapy-related ED, these results merit further investigations.

  20. SU-E-J-166: Sensitivity of Clinically Relevant Dosimetric Parameters to Contouring Uncertainty During Post Implant Dosimetry of Prostate Permanent Seed Implants

    SciTech Connect

    Mashouf, S; Ravi, A; Morton, G; Song, W

    2015-06-15

    Purpose: There is a strong evidence relating post-implant dosimetry for permanent seed prostate brachytherpy to local control rates. The delineation of the prostate on CT images, however, represents a challenge as it is difficult to confidently identify the prostate borders from soft tissue surrounding it. This study aims at quantifying the sensitivity of clinically relevant dosimetric parameters to prostate contouring uncertainty. Methods: The post-implant CT images and plans for a cohort of 43 patients, who have received I–125 permanent prostate seed implant in our centre, were exported to MIM Symphony LDR brachytherapy treatment planning system (MIM Software Inc., Cleveland, OH). The prostate contours in post-implant CT images were expanded/contracted uniformly for margins of ±1.00mm, ±2.00mm, ±3.00mm, ±4.00mm and ±5.00mm (±0.01mm). The values for V100 and D90 were extracted from Dose Volume Histograms for each contour and compared. Results: The mean value of V100 and D90 was obtained as 92.3±8.4% and 108.4±12.3% respectively (Rx=145Gy). V100 was reduced by −3.2±1.5%, −7.2±3.0%, −12.8±4.0%, −19.0±4.8%, − 25.5±5.4% for expanded contours of prostate with margins of +1mm, +2mm, +3mm, +4mm, and +5mm, respectively, while it was increased by 1.6±1.2%, 2.4±2.4%, 2.7±3.2%, 2.9±4.2%, 2.9±5.1% for the contracted contours. D90 was reduced by −6.9±3.5%, −14.5±6.1%, −23.8±7.1%, − 33.6±8.5%, −40.6±8.7% and increased by 4.1±2.6%, 6.1±5.0%, 7.2±5.7%, 8.1±7.3% and 8.1±7.3% for the same set of contours. Conclusion: Systematic expansion errors of more than 1mm may likely render a plan sub-optimal. Conversely contraction errors may Result in labeling a plan likely as optimal. The use of MRI images to contour the prostate should results in better delineation of prostate organ which increases the predictive value of post-op plans. Since observers tend to overestimate the prostate volume on CT, compared with MRI, the impact of the

  1. Molecular imaging of prostate cancer with PET.

    PubMed

    Jadvar, Hossein

    2013-10-01

    Molecular imaging is paving the way for precision and personalized medicine. In view of the significant biologic and clinical heterogeneity of prostate cancer, molecular imaging is expected to play an important role in the evaluation of this prevalent disease. The natural history of prostate cancer spans from an indolent localized process to biochemical relapse after radical treatment with curative intent to a lethal castrate-resistant metastatic disease. The ongoing unraveling of the complex tumor biology of prostate cancer uniquely positions molecular imaging with PET to contribute significantly to every clinical phase of prostate cancer evaluation. The purpose of this article was to provide a concise review of the current state of affairs and potential future developments in the diagnostic utility of PET in prostate cancer.

  2. Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study

    PubMed Central

    Shahabi, Ahva; Corral, Román; Catsburg, Chelsea; Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Koo, Jocelyn; John, Esther M; Ingles, Sue A; Stern, Mariana C

    2014-01-01

    The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This study examined the association between tobacco smoking and PCa risk taking into account polymorphisms in carcinogen metabolism enzyme genes as possible effect modifiers (9 polymorphisms and 1 predicted phenotype from metabolism enzyme genes). The study included cases (n = 761 localized; n = 1199 advanced) and controls (n = 1139) from the multiethnic California Collaborative Case–Control Study of Prostate Cancer. Multivariable conditional logistic regression was performed to evaluate the association between tobacco smoking variables and risk of localized and advanced PCa risk. Being a former smoker, regardless of time of quit smoking, was associated with an increased risk of localized PCa (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0–1.6). Among non-Hispanic Whites, ever smoking was associated with an increased risk of localized PCa (OR = 1.5; 95% CI = 1.1–2.1), whereas current smoking was associated with risk of advanced PCa (OR = 1.4; 95% CI = 1.0–1.9). However, no associations were observed between smoking intensity, duration or pack-year variables, and advanced PCa. No statistically significant trends were seen among Hispanics or African-Americans. The relationship between smoking status and PCa risk was modified by the CYP1A2 rs7662551 polymorphism (P-interaction = 0.008). In conclusion, tobacco smoking was associated with risk of PCa, primarily localized disease among non-Hispanic Whites. This association was modified by a genetic variant in CYP1A2, thus supporting a role for tobacco carcinogens in PCa risk. PMID:25355624

  3. Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study.

    PubMed

    Shahabi, Ahva; Corral, Román; Catsburg, Chelsea; Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Koo, Jocelyn; John, Esther M; Ingles, Sue A; Stern, Mariana C

    2014-12-01

    The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This study examined the association between tobacco smoking and PCa risk taking into account polymorphisms in carcinogen metabolism enzyme genes as possible effect modifiers (9 polymorphisms and 1 predicted phenotype from metabolism enzyme genes). The study included cases (n = 761 localized; n = 1199 advanced) and controls (n = 1139) from the multiethnic California Collaborative Case-Control Study of Prostate Cancer. Multivariable conditional logistic regression was performed to evaluate the association between tobacco smoking variables and risk of localized and advanced PCa risk. Being a former smoker, regardless of time of quit smoking, was associated with an increased risk of localized PCa (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0-1.6). Among non-Hispanic Whites, ever smoking was associated with an increased risk of localized PCa (OR = 1.5; 95% CI = 1.1-2.1), whereas current smoking was associated with risk of advanced PCa (OR = 1.4; 95% CI = 1.0-1.9). However, no associations were observed between smoking intensity, duration or pack-year variables, and advanced PCa. No statistically significant trends were seen among Hispanics or African-Americans. The relationship between smoking status and PCa risk was modified by the CYP1A2 rs7662551 polymorphism (P-interaction = 0.008). In conclusion, tobacco smoking was associated with risk of PCa, primarily localized disease among non-Hispanic Whites. This association was modified by a genetic variant in CYP1A2, thus supporting a role for tobacco carcinogens in PCa risk. PMID:25355624

  4. Localization of linked {sup 125}I seeds in postimplant TRUS images for prostate brachytherapy dosimetry

    SciTech Connect

    Xue Jinyu . E-mail: Jinyu.Xue@mail.tju.edu; Waterman, Frank; Handler, Jay; Gressen, Eric

    2005-07-01

    Purpose: To demonstrate that {sup 125}I seeds can be localized in transrectal ultrasound (TRUS) images obtained with a high-resolution probe when the implant is performed with linked seeds and spacers. Adequate seed localization is essential to the implementation of TRUS-based intraoperative dosimetry for prostate brachytherapy. Methods and Materials: Thirteen preplanned peripherally loaded prostate implants were performed using {sup 125}I seeds and spacers linked together in linear arrays that prevent seed migration and maintain precise seed spacing. A set of two-dimensional transverse images spaced at 0.50-cm intervals were obtained with a high-resolution TRUS probe at the conclusion of the procedure with the patient still under anesthesia. The image set extended from 1.0 cm superior to the base to 1.0 cm inferior to the apex. The visible echoes along each needle track were first localized and then compared with the known construction of the implanted array. The first step was to define the distal and proximal ends of each array. The visible echoes were then identified as seeds or spacers from the known sequence of the array. The locations of the seeds that did not produce a visible echo were interpolated from their known position in the array. A CT scan was obtained after implantation for comparison with the TRUS images. Results: On average, 93% (range, 86-99%) of the seeds were visible in the TRUS images. However, it was possible to localize 100% of the seeds in each case, because the locations of the missing seeds could be determined from the known construction of the arrays. Two factors complicated the interpretation of the TRUS images. One was that the spacers also produced echoes. Although weak and diffuse, these echoes could be mistaken for seeds. The other was that the number of echoes along a needle track sometimes exceeded the number of seeds and spacers implanted. This was attributed to the overall length of the array, which was approximately 0.5 cm

  5. Cost-effectiveness analysis comparing degarelix with leuprolide in hormonal therapy for patients with locally advanced prostate cancer.

    PubMed

    Hatoum, Hind T; Crawford, E David; Nielsen, Sandy Kildegaard; Lin, Swu-Jane; Marshall, Dennis C

    2013-04-01

    Degarelix, approved in the USA in 2008, is a gonadotropin-releasing hormone antagonist, representing one of the latest additions to androgen deprivation therapy (ADT). ADT is used as first-line therapy for locally advanced or metastatic prostate cancer with the aim to reduce testosterone to castrate levels. Like other gonadotropin-releasing hormone-antagonists, degarelix treatment results in rapid decrease in luteinizing hormone, follicle-stimulating hormone and testosterone levels without the associated risk of flare. Using one registration trial for degarelix with leuprolide as the active control, a cost-effectiveness analysis with a Markov model and a 20-year time horizon found the incremental cost-effectiveness ratio for degarelix to be US$245/quality-adjusted life years. Degarelix provides a cost-effective treatment for ADT among patients with locally advanced prostate cancer.

  6. The influence of the local effect model parameters on the prediction of the tumor control probability for prostate cancer

    NASA Astrophysics Data System (ADS)

    Chanrion, M.-A.; Sauerwein, W.; Jelen, U.; Wittig, A.; Engenhart-Cabillic, R.; Beuve, M.

    2014-06-01

    In carbon ion beams, biological effects vary along the ion track; hence, to quantify them, specific radiobiological models are needed. One of them, the local effect model (LEM), in particular version I (LEM I), is implemented in treatment planning systems (TPS) clinically used in European particle therapy centers. From the physical properties of the specific ion radiation, the LEM calculates the survival probabilities of the cell or tissue type under study, provided that some determinant input parameters are initially defined. Mathematical models can be used to predict, for instance, the tumor control probability (TCP), and then evaluate treatment outcomes. This work studies the influence of the LEM I input parameters on the TCP predictions in the specific case of prostate cancer. Several published input parameters and their combinations were tested. Their influence on the dose distributions calculated for a water phantom and for a patient geometry was evaluated using the TPS TRiP98. Changing input parameters induced clinically significant modifications of the mean dose (up to a factor of 3.5), spatial dose distribution, and TCP predictions (up to factor of 2.6 for D50). TCP predictions were found to be more sensitive to the parameter threshold dose (Dt) than to the biological parameters α and β. Additionally, an analytical expression was derived for correlating α, β and Dt, and this has emphasized the importance of \\frac{D_t}{\\alpha /\\beta }. The improvement of radiobiological models for particle TPS will only be achieved when more patient outcome data with well-defined patient groups, fractionation schemes and well-defined end-points are available.

  7. Prostate cancer transrectal HIFU ablation: detection of local recurrences using T2-weighted and dynamic contrast-enhanced MRI.

    PubMed

    Rouvière, Olivier; Girouin, Nicolas; Glas, Ludivine; Ben Cheikh, Alexandre; Gelet, Albert; Mège-Lechevallier, Florence; Rabilloud, Muriel; Chapelon, Jean-Yves; Lyonnet, Denis

    2010-01-01

    The objective was to evaluate T2-weighted (T2w) and dynamic contrast-enhanced (DCE) MRI in detecting local cancer recurrences after prostate high-intensity focused ultrasound (HIFU) ablation. Fifty-nine patients with biochemical recurrence after prostate HIFU ablation underwent T2-weighted and DCE MRI before transrectal biopsy. For each patient, biopsies were performed by two operators: operator 1 (blinded to MR results) performed random and colour Doppler-guided biopsies ("routine biopsies"); operator 2 obtained up to three cores per suspicious lesion on MRI ("targeted biopsies"). Seventy-seven suspicious lesions were detected on DCE images (n = 52), T2w images (n = 2) or both (n = 23). Forty patients and 41 MR lesions were positive at biopsy. Of the 36 remaining MR lesions, 20 contained viable benign glands. Targeted biopsy detected more cancers than routine biopsy (36 versus 27 patients, p = 0.0523). The mean percentages of positive cores per patient and of tumour invasion of the cores were significantly higher for targeted biopsies (p < 0.0001). The odds ratios of the probability of finding viable cancer and viable prostate tissue (benign or malignant) at targeted versus routine biopsy were respectively 3.35 (95% CI 3.05-3.64) and 1.38 (95% CI 1.13-1.63). MRI combining T2-weighted and DCE images is a promising method for guiding post-HIFU biopsy towards areas containing recurrent cancer and viable prostate tissue.

  8. Benign Conditions That Mimic Prostate Carcinoma: MR Imaging Features with Histopathologic Correlation.

    PubMed

    Kitzing, Yu Xuan; Prando, Adilson; Varol, Celi; Karczmar, Gregory S; Maclean, Fiona; Oto, Aytekin

    2016-01-01

    Multiparametric magnetic resonance (MR) imaging combines anatomic and functional imaging techniques for evaluating the prostate and is increasingly being used in diagnosis and management of prostate cancer. A wide spectrum of anatomic and pathologic processes in the prostate may masquerade as prostate cancer, complicating the imaging interpretation. The histopathologic and imaging findings of these potential mimics are reviewed. These entities include the anterior fibromuscular stroma, surgical capsule, central zone, periprostatic vein, periprostatic lymph nodes, benign prostatic hyperplasia (BPH), atrophy, necrosis, calcification, hemorrhage, and prostatitis. An understanding of the prostate zonal anatomy is helpful in distinguishing the anatomic entities from prostate cancer. The anterior fibromuscular stroma, surgical capsule, and central zone are characteristic anatomic features of the prostate with associated low T2 signal intensity due to dense fibromuscular tissue or complex crowded glandular tissue. BPH, atrophy, necrosis, calcification, and hemorrhage all have characteristic features with one or more individual multiparametric MR imaging modalities. Prostatitis constitutes a heterogeneous group of infective and inflammatory conditions including acute and chronic bacterial prostatitis, infective and noninfective granulomatous prostatitis, and malacoplakia. These entities are associated with variable clinical manifestations and are characterized by the histologic hallmark of marked inflammatory cellular infiltration. In some cases, these entities are indistinguishable from prostate cancer at multiparametric MR imaging and may even exhibit extraprostatic extension and lymphadenopathy, mimicking locally advanced prostate cancer. It is important for the radiologists interpreting prostate MR images to be aware of these pitfalls for accurate interpretation. Online supplemental material is available for this article.

  9. Clinical, Laboratorial, and Urodynamic Findings of Prostatic Artery Embolization for the Treatment of Urinary Retention Related to Benign Prostatic Hyperplasia. A Prospective Single-Center Pilot Study

    SciTech Connect

    Antunes, Alberto A.; Carnevale, Francisco C. Motta Leal Filho, Joaquim M. da; Yoshinaga, Eduardo M.; Cerri, Luciana M. O.; Baroni, Ronaldo H.; Marcelino, Antonio S. Z.; Cerri, Giovanni G.; Srougi, Miguel

    2013-08-01

    PurposeThis study was designed to describe the clinical, laboratorial, and urodynamic findings of prostatic artery embolization (PAE) in patients with urinary retention due to benign prostatic hyperplasia (BPH).MethodsA prospective study of 11 patients with urinary retention due to BPH was conducted. Patients underwent physical examination, prostate specific antigen (PSA) measurement, transrectal ultrasound, and magnetic resonance imaging. International prostate symptom score (IPSS), quality of life (QoL), and urodynamic testing were used to assess the outcome before and after 1 year.ResultsClinical success was 91 % (10/11 patients) with a mean follow-up of 22.3 months (range, 12-41 months). At the first year follow-up, the mean IPSS score was 2.8 points (p = 0.04), mean QoL was 0.4 points (p = 0.001), mean PSA decreased from 10.1 to 4.3 ng/mL (p = 0.003), maximum urinary flow (Qmax) improved from 4.2 to 10.8 mL/sec (p = 0.009), and detrusor pressure (Pdet) decreased from 85.7 to 51.5 cm H{sub 2}O (p = 0.007). Before PAE, Bladder Outlet Obstruction Index (BOOI) showed values >40 in 100 % of patients. After PAE, 30 % of patients were >40 (obstructed), 40 % were between 20 and 40 (undetermined), and 30 % were <20 (unobstructed). Patients with a BOOI <20 had higher PSA values at 1-day after PAE.ConclusionsClinical and urodynamic parameters improved significantly after PAE in patients with acute urinary retention due to BPH. Total PSA at day 1 after PAE was higher in patients with unobstructed values in pressure flow studies.

  10. Prognostic role of genetic biomarkers in clinical progression of prostate cancer

    PubMed Central

    Alvarez-Cubero, Maria Jesus; Martinez-Gonzalez, Luis Javier; Saiz, Maria; Carmona-Saez, Pedro; Alvarez, Juan Carlos; Pascual-Geler, Manrique; Lorente, Jose Antonio; Cozar, Jose Manuel

    2015-01-01

    The aim of this study was to analyze the use of 12 single-nucleotide polymorphisms in genes ELAC2, RNASEL and MSR1 as biomarkers for prostate cancer (PCa) detection and progression, as well as perform a genetic classification of high-risk patients. A cohort of 451 men (235 patients and 216 controls) was studied. We calculated means of regression analysis using clinical values (stage, prostate-specific antigen, Gleason score and progression) in patients and controls at the basal stage and after a follow-up of 72 months. Significantly different allele frequencies between patients and controls were observed for rs1904577 and rs918 (MSR1 gene) and for rs17552022 and rs5030739 (ELAC2). We found evidence of increased risk for PCa in rs486907 and rs2127565 in variants AA and CC, respectively. In addition, rs627928 (TT–GT), rs486907 (AG) and rs3747531 (CG–CC) were associated with low tumor aggressiveness. Some had a weak linkage, such as rs1904577 and rs2127565, rs4792311 and rs17552022, and rs1904577 and rs918. Our study provides the proof-of-principle that some of the genetic variants (such as rs486907, rs627928 and rs2127565) in genes RNASEL, MSR1 and ELAC2 can be used as predictors of aggressiveness and progression of PCa. In the future, clinical use of these biomarkers, in combination with current ones, could potentially reduce the rate of unnecessary biopsies and specific treatments. PMID:26251261

  11. [Bilateral testicular metastasis of cancer of the prostate].

    PubMed

    el Moussaoui, A; Sarf, I; Dakir, M; Zamiati, S; Benjelloun, S

    1997-01-01

    Testicular metastasis of prostate cancer rarely occurs. Bilateral localization is exceptional. We report a new case of prostate adenocarcinoma with bilateral testicular metastasis. The diagnosis was made on clinical and ultrasonic arguments, and confirmed on the pathological specimen. Treatment consisted in a bilateral orchidectomy, associated with nonsteroid androgens.

  12. The cost effectiveness of a nurse-led shared-care prostate assessment clinic.

    PubMed Central

    Dasgupta, P.; Drudge-Coates, L.; Smith, K.; Booth, C. M.

    2002-01-01

    OBJECTIVE: Nurse-led prostate clinics (NPCs) have proved to be a highly effective method of assessing patients with lower urinary tract symptoms (LUTS) and most urology units now run such clinics. However, it was not known whether they are cost-effective and this analysis ansWers that question. PATIENTS AND METHODS: During one year, a trained urology nurse assessed 1,080 patients in our NPC following GP referral using a standard pro forma. Costs included those incurred for the salary of a grade D nurse at 30 min per patient, all investigations, indirect charges and overheads. This was compared to the cost of seeing all patients in clinic directly, either by a consultant, staff grade urologist or registrar. Of these 1,080 patients, 350 were sent back to their GPs after NPC assessment. RESULTS: The NPC cost of 44.25 pounds per patient compared favourably with an average medical out-patient clinic cost of 50.46 pounds per patient, yielding an actual annual saving of 6,706.80 pounds. Since a third of the patients assessed in the NPC were sent directly back to primary care, saving the cost of a medical follow-up appointment, the true savings in secondary care were 17,661.00 pounds (50.46 x 350pounds), giving a total annual saving of 24,367.80 pounds. CONCLUSIONS: A nurse-led shared-care prostate clinic is a cost effective, thorough and speedy method of assessing men presenting with suspected bladder outflow obstruction. The approach used has a wider generic, cost-benefit potential for the NHS. PMID:12398125

  13. Results of a study to correlate serum prostate specific antigen and reproductive hormone levels in patients with localized prostate cancer.

    PubMed Central

    Vijayakumar, S.; Quadri, S. F.; Dong, L.; Ignacio, L.; Kathuria, I. N.; Sutton, H.; Halpern, H.

    1995-01-01

    This cross-sectional study was undertaken to determine whether serum hormones (free testosterone, androstenedione, luteinizing hormone, or prolactin) have any influence on serum prostate specific antigen (PSA) levels in patients with stage A-C prostate cancer. Blood samples were collected prior to any treatment in 36 patients; in 19 (group 1), three blood samples were collected 10 minutes apart between 9:00 AM and 9:30 AM for each patient and pooled together to avoid diurnal and episodic variation in serum testosterone values. In the remaining patients, only one sample could be collected (group 2). Free testosterone, androstenedione, luteinizing hormone, prolactin, and PSA levels were determined with appropriate radioimmunoassay techniques. Statistical analyses were performed separately for groups 1 and 2, and then with pooled data. None of the hormones in any of the analyses showed any association to serum PSA values except for prolactin for the pooled data and for group 2. This statistical significance for prolactin disappeared on multivariate analysis. There were 21 African-American men and 15 whites in the study; no racial differences in hormonal levels were found except for lower luteinizing hormone levels in African Americans in group 2 and pooled data. No differences were found between group 1 and group 2 in the mean serum prolactin and luteinizing hormone values. Serum free testosterone, androstenedione, and luteinizing hormone appeared to have no influence on serum PSA values in nonmetastatic cancer patients. Serum prolactin values were inversely associated with PSA values in univariate analysis for the pooled data; this disappeared in multivariate analysis. Unlike other studies that found higher serum testosterone levels in African-American college students than whites, no such differences were seen in this age group. Luteinizing hormone was lower in African-American men than in whites in the pooled study population. Further studies are needed to clarify

  14. Multiparametric-MRI in diagnosis of prostate cancer

    PubMed Central

    Ghai, Sangeet; Haider, Masoom A.

    2015-01-01

    Multiparametric-magnetic resonance imaging (mp-MRI) has shown promising results in diagnosis, localization, risk stratification and staging of clinically significant prostate cancer. It has also opened up opportunities for focal treatment of prostate cancer. Combinations of T2-weighted imaging, diffusion imaging, perfusion (dynamic contrast-enhanced imaging) and spectroscopic imaging have been used in mp-MRI assessment of prostate cancer, but T2 morphologic assessment and functional assessment by diffusion imaging remains the mainstay for prostate cancer diagnosis on mp-MRI. Because assessment on mp-MRI can be subjective, use of the newly developed standardized reporting Prostate Imaging and Reporting Archiving Data System scoring system and education of specialist radiologists are essential for accurate interpretation. This review focuses on the present status of mp-MRI in prostate cancer and its evolving role in the management of prostate cancer. PMID:26166962

  15. [Epidemiology of prostate cancer in China: an overview and clinical implication].

    PubMed

    Ye, Dingwei; Zhu, Yao

    2015-04-01

    Prostate cancer is a currently common disease in Chinese male. The incidence is increasing rapidly in urban area and the mortality is high in rural area. According to characteristics of disease stage, advancement in early diagnosis of prostate cancer is the key to improve prostate cancer survival in China. Because of the remarkable disparity in economic and health care across mainland China, a selective prostate cancer screen approach may be a better alternative to spread. Therefore, indepth researches in optimization of prostate specific antigen screen and validation biomarkers of aggressive prostate cancer should be advocated. Furthermore, physicians should take a more active role in population education.

  16. Minimal Benefit of an Endorectal Balloon for Prostate Immobilization as Verified by Daily Localization

    SciTech Connect

    Hung, Arthur Y.; Garzotto, Mark; Kaurin, Darryl

    2011-07-01

    We wanted to investigate whether using an endorectal balloon (ERB) in lieu of image guidance is reasonable. We compared daily prostate motion in 2 cohorts of patients with fiducial markers implanted in the prostate, one group with the ERB and the other without. Twenty-nine patients were treated using intensity-modulated radiation therapy: 14 with an ERB, and 15 without. All had fiducial markers placed in the prostate. We reviewed the daily displacements necessary to place the isocenter on the prostate as determined by portal imaging. In addition, we used the data to determine whether there is a change in prostate motion over the treatment course. The average prostate displacement for patients treated without an ERB was slightly greater than the average displacement for patients treated with the ERB. However, the difference observed with the ERB was not statistically significant (p > 0.05). The margins necessary to encompass the prostate 95% of the time for the patients treated without an ERB in the lateral, cranio/caudal, and anterior/posterior dimensions would be 4.8, 12.1, and 15.2 mm, respectively. When using the ERB, the margins necessary would be 4.1, 10.4, and 11 mm, respectively. Prostate motion in the anterior-posterior direction actually increased over the course of treatment in patients without an ERB. This increase was prevented by use of the ERB. Day-to-day variability of the position of the prostate is reduced in all dimensions with the water-filled ERB, but not significantly statistically. Use of the water-filled ERB did not obviate performing some form of image guidance daily.

  17. Importance of Local Control in Early-Stage Prostate Cancer: Outcomes of Patients With Positive Post-Radiation Therapy Biopsy Results Treated in RTOG 9408

    SciTech Connect

    Krauss, Daniel J.; Hu, Chen; Bahary, Jean-Paul; Souhami, Luis; Gore, Elizabeth M.; Chafe, Susan Maria Jacinta; Leibenhaut, Mark H.; Narayan, Samir; Torres-Roca, Javier; Michalski, Jeff; Zeitzer, Kenneth L.; Donavanik, Viroon; Sandler, Howard; McGowan, David G.; Jones, Christopher U.; Shipley, William U.

    2015-07-15

    Purpose: The purpose of this study was to assess the association between positive post-radiation therapy (RT) biopsy results and subsequent clinical outcomes in males with localized prostate cancer. Methods and Materials: Radiation Therapy Oncology Group study 94-08 analyzed 1979 males with prostate cancer, stage T1b-T2b and prostate-specific antigen concentrations of ≤20 ng/dL, to investigate whether 4 months of total androgen suppression (TAS) added to RT improved survival compared to RT alone. Patients randomized to receive TAS received flutamide with luteinizing hormone releasing hormone (LHRH) agonist. According to protocol, patients without evidence of clinical recurrence or initiation of additional endocrine therapy underwent repeat prostate biopsy 2 years after RT completion. Statistical analysis was performed to evaluate the impact of positive post-RT biopsy results on clinical outcomes. Results: A total of 831 patients underwent post-RT biopsy, 398 were treated with RT alone and 433 with RT plus TAS. Patients with positive post-RT biopsy results had higher rates of biochemical failure (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.3-2.1) and distant metastasis (HR = 2.4; 95% CI = 1.3-4.4) and inferior disease-specific survival (HR = 3.8; 95% CI = 1.9-7.5). Positive biopsy results remained predictive of such outcomes after correction for potential confounders such as Gleason score, tumor stage, and TAS administration. Prior TAS therapy did not prevent elevated risk of adverse outcome in the setting of post-RT positive biopsy results. Patients with Gleason score ≥7 with a positive biopsy result additionally had inferior overall survival compared to those with a negative biopsy result (HR = 1.56; 95% CI = 1.04-2.35). Conclusions: Positive post-RT biopsy is associated with increased rates of distant metastases and inferior disease-specific survival in patients treated with definitive RT and was associated with inferior overall

  18. Review. Facts and fiction of phytotherapy for prostate cancer: a critical assessment of preclinical and clinical data.

    PubMed

    Von Löw, Eva C; Perabo, Frank G E; Siener, Roswitha; Müller, Stefan C

    2007-01-01

    The objective of this work was to substantially review all preclinical and clinical data on phytochemicals, such as genistein, lycopene, curcumin, epigallocatechin-gallate, and resveratrol, in terms of their effects as a potential treatment of prostate cancer. It is known, that prostate cancer patients increasingly use complementary and alternative medicines in the hope of preventing or curing cancer. The preclinical data for the phytochemicals presented in this review show a remarkable efficacy against prostate cancer cells in vitro, with molecular targets ranging from cell cycle regulation to induction of apoptosis. In addition, well-conducted animal experiments support the belief that these substances might have a clinical activity on human cancer. However, it is impossible to make definite statements or conclusions on the clinical efficacy in cancer patients because of the great variability and differences of the study designs, small patient numbers, short treatment duration and lack of a standardised drug formulation. Although some results from these clinical studies seem encouraging, reliable or long-term data on tumor recurrence, disease progression and survival are unknown. At present, there is no convincing clinical proof or evidence that the cited phythochemicals might be used in an attempt to cure cancer of the prostate. PMID:17436567

  19. Brachytherapy versus prostatectomy in localized prostate cancer: Results of a French multicenter prospective medico-economic study

    SciTech Connect

    Buron, Catherine; Le Vu, Beatrice; Cosset, Jean-Marc; Peiffert, Didier; Delannes, Martine; Flam, Thierry; Guerif, Stephane; Salem, Naji; Chauveinc, Laurent; Livartowski, Alain . E-mail: alain.livartowski@curie.net

    2007-03-01

    Purpose: To prospectively compare health-related quality of life (HRQOL), patient-reported treatment-related symptoms, and costs of iodine-125 permanent implant interstitial brachytherapy (IB) with those of radical prostatectomy (RP) during the first 2 years after these treatments for localized prostate cancer. Methods and Materials: A total of 435 men with localized low-risk prostate cancer, from 11 French hospitals, treated with IB (308) or RP (127), were offered to complete the European Organization for Research and Treatment of Cancer core Quality of Life Questionnaire QLQ-C30 version 3 (EORTC QLQ-C30) and the prostate cancer specific EORTC QLQ-PR25 module before and at the end of treatment, 2, 6, 12, 18, and 24 months after treatment. Repeated measures analysis of variance and analysis of covariance were conducted on HRQOL changes. Comparative cost analysis covered initial treatment, hospital follow-up, outpatient and production loss costs. Results: Just after treatment, the decrease of global HRQOL was less pronounced in the IB than in the RP group, with a 13.5 points difference (p < 0.0001). A difference slightly in favor of RP was observed 6 months after treatment (-7.5 points, p = 0.0164) and was maintained at 24 months (-8.2 points, p = 0.0379). Impotence and urinary incontinence were more pronounced after RP, whereas urinary frequency, urgency, and urination pain were more frequent after IB. Mean societal costs did not differ between IB ( Euro 8,019 at T24) and RP ( Euro 8,715 at T24, p = 0.0843) regardless of the period. Conclusions: This study suggests a similar cost profile in France for IB and RP but with different HRQOL and side effect profiles. Those findings may be used to tailor localized prostate cancer treatments to suit individual patients' needs.

  20. Case-Matched comparison of contemporary radiation therapy to surgery in patients with locally advanced prostate cancer

    SciTech Connect

    Fletcher, Sophie G.; Mills, Stacey E.; Smolkin, Mark E.; Theodorescu, Dan . E-mail: dt9d@virginia.edu

    2006-11-15

    Purpose: Few studies critically compare current radiotherapy techniques to surgery for patients with locally advanced prostate cancer, despite an urgent need to determine which approach offers superior cancer control. Our objective was to compare rates of biochemical relapse-free survival (BFS) and surrogates of disease specific survival among men with high risk adenocarcinoma of the prostate as a function of treatment modality. Methods and Materials: Retrospective data from 409 men with prostate-specific antigen (PSA) {>=}10 or Gleason 7-10 or Stage {>=}T2b cancer treated uniformly at one university between March 1988 and December 2000 were analyzed. Patients had undergone radical prostatectomy (RP), brachytherapy implant alone (BTM), or external beam radiotherapy with brachytherapy boost with short-term neoadjuvant and adjuvant androgen deprivation therapy (BTC). From the total study population a 1:1 matched-cohort analysis (208 patients matched via prostate-specific antigen, Gleason score) comparing RP with BTC was performed as well. Results: Estimated 4-year BFS rates were superior for patients treated with BTC (BTC 72%, BTM 25%, RP 53%; p < 0.001). Matched analysis of BTC vs. RP confirmed these results (BTC 73%, BTM 55%; p = 0.010). Relative risk (RR) of biochemical relapse for BTM and BTC compared with RP were 2.92 (1.95-4.36) and 0.56 (0.36-0.87) (p < 0.001, p = 0.010). RR for BTC from the matched cohort analysis was 0.44 (0.26-0.74; p = 0.002). Conclusions: High-risk prostate cancer patients receiving multimodality radiation therapy (BTC) display apparently superior BFS compared with those receiving surgery (RP) or brachytherapy alone (BTM)

  1. Comparison of High-Dose Proton Radiotherapy and Brachytherapy in Localized Prostate Cancer: A Case-Matched Analysis

    SciTech Connect

    Coen, John J.; Zietman, Anthony L.; Rossi, Carl J.; Grocela, Joseph A.; Efstathiou, Jason A.; Yan, Yan; Shipley, William U.

    2012-01-01

    Purpose: To report a case-matched analysis comparing high-dose external-beam radiation (EBRT) for prostate cancer delivered on Proton Radiation Oncology Group (PROG) 95-09, a randomized trial, with permanent prostate brachytherapy over the same era. Methods: From 1996 to 1999, 196 patients were accrued to the high-dose arm (79.2 Gray equivalent (GyE) using photons and protons) of PROG 95-09 at the Massachusetts General Hospital and Loma Linda University Medical Center. Entry criteria specified T1-2 and prostate-specific antigen {<=}15 ng/mL. When Gleason score >7 was excluded, 177 men were left for case matching. At Massachusetts General Hospital, 203 similar patients were treated by a single brachytherapist from 1997 to 2002. Minimum follow-up was 3 years. Case matching, based on T stage, Gleason score, prostate-specific antigen, and age resulted in 141 matches (282 patients). Median follow-up was 8.6 and 7.4 years for EBRT and brachytherapy, respectively. The primary endpoint was biochemical failure (BF). Results: Using the Phoenix definition, the 8-year BF rates were 7.7% and 16.1% for EBRT and brachytherapy, respectively (p = 0.42). A stratified analysis was performed by risk group. In the EBRT group, 113 and 28 patients were low and intermediate risk, respectively. In the brachytherapy group, 118 and 23 were. When stratified by risk group, the BF rates were similar by either technique. Conclusions: High-dose EBRT and brachytherapy result in similar BF rates for men with localized prostate cancer. Comparative quality-of-life and cost-effectiveness studies are warranted.

  2. Clinical validity and utility of genetic risk scores in prostate cancer

    PubMed Central

    Helfand, Brian T; Kearns, James; Conran, Carly; Xu, Jianfeng

    2016-01-01

    Current issues related to prostate cancer (PCa) clinical care (e.g., over-screening, over-diagnosis, and over-treatment of nonaggressive PCa) call for risk assessment tools that can be combined with family history (FH) to stratify disease risk among men in the general population. Since 2007, genome-wide association studies (GWASs) have identified more than 100 SNPs associated with PCa susceptibility. In this review, we discuss (1) the validity of these PCa risk-associated SNPs, individually and collectively; (2) the various methods used for measuring the cumulative effect of multiple SNPs, including genetic risk score (GRS); (3) the adequate number of SNPs needed for risk assessment; (4) reclassification of risk based on evolving numbers of SNPs used to calculate genetic risk, (5) risk assessment for men from various racial groups, and (6) the clinical utility of genetic risk assessment. In conclusion, data available to date support the clinical validity of PCa risk-associated SNPs and GRS in risk assessment among men with or without FH. PCa risk-associated SNPs are not intended for diagnostic use; rather, they should be used the same way as FH. Combining GRS and FH can significantly improve the performance of risk assessment. Improved risk assessment may have important clinical utility in targeted PCa testing. However, clinical trials are urgently needed to evaluate this clinical utility as well as the acceptance of GRS by patients and physicians. PMID:27297129

  3. Histone deacetylase inhibitors in castration-resistant prostate cancer: molecular mechanism of action and recent clinical trials

    PubMed Central

    Kaushik, Dharam; Vashistha, Vishal; Isharwal, Sudhir; Sediqe, Soud A.; Lin, Ming-Fong

    2015-01-01

    Historically, androgen-deprivation therapy has been the cornerstone for treatment of metastatic prostate cancer. Unfortunately, nearly majority patients with prostate cancer transition to the refractory state of castration-resistant prostate cancer (CRPC). Newer therapeutic agents are needed for treating these CRPC patients that are unresponsive to androgen deprivation and/or chemotherapy. The histone deacetylase (HDAC) family of enzymes limits the expression of genomic regions by improving binding between histones and the DNA backbone. Modulating the role of HDAC enzymes can alter the cell’s regulation of proto-oncogenes and tumor suppressor genes, thereby regulating potential neoplastic proliferation. As a result, histone deacetylase inhibitors (HDACi) are now being evaluated for CRPC or chemotherapy-resistant prostate cancer due to their effects on the expression of the androgen receptor gene. In this paper, we review the molecular mechanism and functional target molecules of different HDACi as applicable to CRPC as well as describe recent and current clinical trials involving HDACi in prostate cancer. To date, four HDAC classes comprising 18 isoenzymes have been identified. Recent clinical trials of vorinostat, romidepsin, and panobinostat have provided cautious optimism towards improved outcomes using these novel therapeutic agents for CPRC patients. Nevertheless, no phase III trial has been conducted to cement one of these drugs as an adjunct to androgen-deprivation therapy. Consequently, further investigation is necessary to delineate the benefits and drawbacks of these medications. PMID:26622323

  4. Diagnostic imaging work-up for disease relapse after radical treatment for prostate cancer: how to differentiate local from systemic disease? The urologist point of view.

    PubMed

    Schiavina, R; Brunocilla, E; Borghesi, M; Vagnoni, V; Castellucci, P; Nanni, C; Ceci, F; Gacci, M; Martorana, G; Fanti, S

    2013-01-01

    About 40% of all patients undergoing radical treatment for localized prostate cancer (PCa) develop biochemical relapse (BCR) during lifetime but only 10-20% of them will show clinically detectable recurrences. Prostatic bed, pelvic or retroperitoneal lymph nodes (LN) and bones (especially the spine) are the sites where we must focus our attention in the early phase of PSA relapse. Time to PSA relapse, PSA kinetics, pathological Gleason score and pathological stage are the main factors related to the likelihood of local vs. distant relapse. Before an extensive diagnostic work-up in patients with BCR, is mandatory to understand if there is a therapeutic consequence or not for the patient. Current imaging techniques have some potential but many limits are yet encountered in the diagnosis of disease relapse. Transrectal ultrasound (TRUS) and Multiparametric Magnetic Resonance Imaging (MRI) have low accuracy in the detection of the recurrence. Today, Choline PET/CT may visualize the site of recurrence earlier, with better accuracy than conventional imaging, in a single step and even in the presence of low PSA level. In recent years, the new radiotracer (18)F-FACBC has been proposed as a possible alternative radiopharmaceutical to detect PCa relapse. From a clinical point of view, first clinical studies showed very promising and reproducible results with an improvement in sensitivity is about 20-25% with respect to Choline PET/CT, rendering the FACBC the possible radiotracer of the future for PCa. In conclusion, many improvements have been recently achieved in imaging techniques for PCa restaging, essentially in Nuclear Medicine and MRI, but negative results remain in many cases. Low sensitivity, costs, availability of technologies and confirmation of the results remain the major limitations in most cases.

  5. Localized scleroderma: clinical spectrum and therapeutic update*

    PubMed Central

    Careta, Mariana Figueiroa; Romiti, Ricardo

    2015-01-01

    Scleroderma is a rare connective tissue disease that is manifested by cutaneous sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement, and localized scleroderma or morphea which classically presents benign and self-limited evolution and is confined to the skin and/or underlying tissues. Localized scleroderma is a rare disease of unknown etiology. Recent studies show that the localized form may affect internal organs and have variable morbidity. Treatment should be started very early, before complications occur due to the high morbidity of localized scleroderma. In this review, we report the most important aspects and particularities in the treatment of patients diagnosed with localized scleroderma. PMID:25672301

  6. 70 Gy Versus 80 Gy in Localized Prostate Cancer: 5-Year Results of GETUG 06 Randomized Trial;Prostate cancer; Dose escalation; Conformal radiotherapy; Randomized trial

    SciTech Connect

    Beckendorf, Veronique; Guerif, Stephane; Le Prise, Elisabeth; Cosset, Jean-Marc; Bougnoux, Agnes; Chauvet, Bruno; Salem, Naji; Chapet, Olivier; Bourdain, Sylvain; Bachaud, Jean-Marc; Maingon, Philippe; Hannoun-Levi, Jean-Michel; Malissard, Luc; Simon, Jean-Marc; Pommier, Pascal; Hay, Men; Dubray, Bernard; Lagrange, Jean-Leon; Luporsi, Elisabeth; Bey, Pierre

    2011-07-15

    Purpose: To perform a randomized trial comparing 70 and 80 Gy radiotherapy for prostate cancer. Patients and Methods: A total of 306 patients with localized prostate cancer were randomized. No androgen deprivation was allowed. The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions. Toxicity was graded using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective, objective, management, analytic scales (LENT-SOMA) scales. The patients' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item cancer-specific and 25-item prostate-specific modules. Results: The median follow-up was 61 months. According to the 1997-American Society for Therapeutic Radiology and Oncology definition, the 5-year biochemical relapse rate was 39% and 28% in the 70- and 80-Gy arms, respectively (p = .036). Using the Phoenix definition, the 5-year biochemical relapse rate was 32% and 23.5%, respectively (p = .09). The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level >15 ng/mL. At the last follow-up date, 26 patients had died, 10 of their disease and none of toxicity, with no differences between the two arms. According to the Radiation Therapy Oncology Group scale, the Grade 2 or greater rectal toxicity rate was 14% and 19.5% for the 70- and 80-Gy arms (p = .22), respectively. The Grade 2 or greater urinary toxicity was 10% at 70 Gy and 17.5% at 80 Gy (p = .046). Similar results were observed using the LENT-SOMA scale. Bladder toxicity was more frequent at 80 Gy than at 70 Gy (p = .039). The quality-of-life questionnaire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms. Conclusion: High-dose radiotherapy provided a

  7. Interfraction rotation of the prostate as evaluated by kilovoltage X-ray fiducial marker imaging in intensity-modulated radiotherapy of localized prostate cancer

    SciTech Connect

    Graf, Reinhold; Boehmer, Dirk; Budach, Volker; Wust, Peter

    2012-01-01

    To quantify the daily rotation of the prostate during a radiotherapy course using stereoscopic kilovoltage (kV) x-ray imaging and intraprostatic fiducials for localization and positioning correction. From 2005 to 2009, radio-opaque fiducial markers were inserted into 38 patients via perineum into the prostate. The ExacTrac/Novalis Body X-ray 6-day image acquisition system (ET/NB; BrainLab AG, Feldkirchen, Germany) was used to determine and correct the target position. During the first period in 10 patients we recorded all rotation errors but used only Y (table) for correction. For the next 28 patients we used for correction all rotational coordinates, i.e., in addition Z (superior-inferior [SI] or roll) and X (left-right [LR] or tilt/pitch) according to the fiducial marker position by use of the Robotic Tilt Module and Varian Exact Couch. Rotation correction was applied above a threshold of 1 Degree-Sign displacement. The systematic and random errors were specified. Overall, 993 software-assisted rotational corrections were performed. The interfraction rotation errors of the prostate as assessed from the radiodense surrogate markers around the three axes Y, Z, and X were on average 0.09, -0.52, and -0.01 Degree-Sign with standard deviations of 2.01, 2.30, and 3.95 Degree-Sign , respectively. The systematic uncertainty per patient for prostate rotation was estimated with 2.30, 1.56, and 4.13 Degree-Sign and the mean random components with 1.81, 2.02, and 3.09 Degree-Sign . The largest rotational errors occurred around the X-axis (pitch), but without preferring a certain orientation. Although the error around Z (roll) can be compensated on average by a transformation with 4 coordinates, a significant error around X remains and advocates the full correction with 6 coordinates. Rotational errors as assessed via daily stereoscopic online imaging are significant and dominate around X. Rotation possibly degrades the dosimetric coverage of the target volume and may require

  8. [Chemotherapy for prostate cancer].

    PubMed

    Rauchenwald, Michael; De Santis, Maria; Fink, Eleonore; Höltl, Wolfgang; Kramer, Gero; Marei, Isabella-Carolina; Neumann, Hans-Jörg; Reissigl, Andreas; Schmeller, Nikolaus; Stackl, Walter; Hobisch, Alfred; Krainer, Michael

    2008-01-01

    For many years the benefit of chemotherapy in patients with prostate cancer was thought to be limited to palliation of late-stage disease, and thus this treatment option only became involved in patient care towards the end of the disease process, if at all. However, two landmark phase-III trials with docetaxel-based therapy (TAX 327 and Southwest Oncology Group, SWOG, 9916) have shown a survival benefit for patients with hormone refractory prostate cancer (HRPC) thus prompting a change in patterns of care. With raising interest for chemotherapeutic options and clinical trials for new drugs and new indications (neoadjuvant therapy, adjuvant therapy, increasing PSA levels after local treatment, and hormone sensitive cancer) under way our goal was to review within the context of a multidisciplinary team the available evidence and explore the standard for the medical treatment of prostate cancer outside of clinical trials. We are carefully evaluating the current treatment recommendations based on the available evidence and highlight potential future treatment options but also discuss important clinical topics (treatment until progression versus the advantage of chemo holidays, definition of particular patient subgroups and potential second line options) for which there are no clear cut answers to date. The role and importance of radiotherapy, biphosphonate treatment and the medical management of pain and side effects is also discussed. The multitude of treatment options for patients with advanced prostate cancer clearly asks for a close collaboration between urologists, medical oncologists and radiation therapists. PMID:18726672

  9. Image-guided adaptive radiation therapy (IGART): Radiobiological and dose escalation considerations for localized carcinoma of the prostate

    SciTech Connect

    Song, William; Schaly, Bryan; Bauman, Glenn; Battista, Jerry; Van Dyk, Jake

    2005-07-15

    The goal of this work was to evaluate the efficacy of various image-guided adaptive radiation therapy (IGART) techniques to deliver and escalate dose to the prostate in the presence of geometric uncertainties. Five prostate patients with 15-16 treatment CT studies each were retrospectively analyzed. All patients were planned with an 18 MV, six-field conformal technique with a 10 mm margin size and an initial prescription of 70 Gy in 35 fractions. The adaptive strategy employed in this work for patient-specific dose escalation was to increase the prescription dose in 2 Gy-per-fraction increments until the rectum normal tissue complication probability (NTCP) reached a level equal to that of the nominal plan NTCP (i.e., iso-NTCP dose escalation). The various target localization techniques simulated were: (1) daily laser-guided alignment to skin tattoo marks that represents treatment without image-guidance, (2) alignment to bony landmarks with daily portal images, and (3) alignment to the clinical target volume (CTV) with daily CT images. Techniques (1) and (3) were resimulated with a reduced margin size of 5 mm to investigate further dose escalation. When delivering the original clinical prescription dose of 70 Gy in 35 fractions, the 'CTV registration' technique yielded the highest tumor control probability (TCP) most frequently, followed by the 'bone registration' and 'tattoo registration' techniques. However, the differences in TCP among the three techniques were minor when the margin size was 10 mm ({<=}1.1%). Reducing the margin size to 5 mm significantly degraded the TCP values of the 'tattoo registration' technique in two of the five patients, where a large difference was found compared to the other techniques ({<=}11.8%). The 'CTV registration' technique, however, did maintain similar TCP values compared to their 10 mm margin counterpart. In terms of normal tissue sparing, the technique producing the lowest NTCP varied from patient to patient. Reducing the

  10. A Dosimetric Comparison between Conventional Fractionated and Hypofractionated Image-guided Radiation Therapies for Localized Prostate Cancer

    PubMed Central

    Li, Ming; Li, Gao-Feng; Hou, Xiu-Yu; Gao, Hong; Xu, Yong-Gang; Zhao, Ting

    2016-01-01

    Background: Image-guided radiation therapy (IGRT) is the preferred method for curative treatment of localized prostate cancer, which could improve disease outcome and reduce normal tissue toxicity reaction. IGRT using cone-beam computed tomography (CBCT) in combination with volumetric-modulated arc therapy (VMAT) potentially allows smaller treatment margins and dose escalation to the prostate. The aim of this study was to compare the difference of dosimetric diffusion in conventional IGRT using 7-field, step-and-shoot intensity-modulated radiation therapy (IMRT) and hypofractionated IGRT using VMAT for patients with localized prostate cancer. Methods: We studied 24 patients who received 78 Gy in 39 daily fractions or 70 Gy in 28 daily fractions to their prostate with/without the seminal vesicles using IMRT (n = 12) or VMAT (n = 12) for prostate cancer between November 2013 and October 2015. Image guidance was performed using kilovoltage CBCT scans equipped on the linear accelerator. Offline planning was performed using the daily treatment images registered with simulation computed tomography (CT) images. A total of 212 IMRT plans in conventional cohort and 292 VMAT plans in hypofractionated cohort were enrolled in the study. Dose distributions were recalculated on CBCT images registered with the planning CT scanner. Results: Compared with 7-field, step-and-shoot IMRT, VMAT plans resulted in improved planning target volume (PTV) D95% (7663.17 ± 69.57 cGy vs. 7789.17 ± 131.76 cGy, P < 0.001). VMAT reduced the rectal D25 (P < 0.001), D35 (P < 0.001), and D50 (P < 0.001), bladder V50 (P < 0.001), D25 (P = 0.002), D35 (P = 0.028), and D50 (P = 0.029). However, VMAT did not statistically significantly reduce the rectal V50, compared with 7-field, step-and-shoot IMRT (25.02 ± 5.54% vs. 27.43 ± 8.79%, P = 0.087). Conclusions: To deliver the hypofractionated radiotherapy in prostate cancer, VMAT significantly increased PTV D95% dose and decreased the dose of radiation

  11. Clinical application of radiophotoluminescent glass dosimeter for dose verification of prostate HDR procedure

    SciTech Connect

    Hsu, Shih-Ming; Yeh, Chien-Yi; Yeh, Tien-Chi; Hong, Ji-Hong; Tipton, Annie Y. H.; Chen, Wei-Li; Sun, Shung-Shung; Huang, David Y. C.

    2008-12-15

    High dose rate brachytherapy (HDR-BT) is one of the many modalities for prostate cancer treatment. Due to the nature of HDR-BT, in vivo dosimetry is feasible and can be used to verify consistent dose delivery. In order to validate a dose verification system for HDR-BT prostate cancer treatment, a radiophotoluminescent glass dosimeter (RPLGD) was used and the measurements were compared with those from a thermoluminescent dosimeter. The RPLGD shows many advantages in HDR-BT dose measurement, such as repeatability, stability, and small effective size. These advantages make the RPLGD a superior option for use as a dosimeter in HDR-BT. The results described here show that the difference between the measured dose and the treatment planned dose is less than 5%. A Monte Carlo simulation for the dose was performed using Monte Carlo N -particle to investigate position error. This study concludes that the RPLGD is a promising and reliable dosimeter for HDR-BT in vivo dosimetry with clinically acceptable accuracy.

  12. Prostate Cancer in a Male with Holt-Oram Syndrome: First Clinical Association of the TBX5 Mutation.

    PubMed

    Aherne, Noel J; Rangaswamy, Guhan; Thirion, Pierre

    2013-01-01

    Holt-Oram syndrome is an autosomal dominant disorder which is caused by mutations of TBX5 and is characterised by cardiac and skeletal abnormalities. TBX5 is part of the T-box gene family and is thought to upregulate tumour cell proliferation and metastasis when mutated. We report the first clinical case of prostate cancer in an individual with Holt Oram syndrome.

  13. Urinary microRNA-based signature improves accuracy of detection of clinically relevant prostate cancer within the prostate-specific antigen grey zone.

    PubMed

    Salido-Guadarrama, Alberto Ivan; Morales-Montor, Jorge Gustavo; Rangel-Escareño, Claudia; Langley, Elizabeth; Peralta-Zaragoza, Oscar; Cruz Colin, Jose Luis; Rodriguez-Dorantes, Mauricio

    2016-06-01

    At present, prostate-specific antigen (PSA) is used as a clinical biomarker for prostate cancer (PCa) diagnosis; however, a large number of patients with benign prostate hyperplasia (BPH) with PSA levels in the 'gray area' (4-10 ng/ml) are currently subjected to unnecessary biopsy due to overdiagnosis. Certain microRNAs (miRs) have been proven to be useful biomarkers, several of which are detectable in bodily fluids. The present study identified and validated a urinary miR‑based signature to enhance the specificity of PCa diagnosis and to reduce the number of patients with benign conditions undergoing biopsy. Seventy‑three urine samples from Mexican patients with diagnosis of PCa with a Gleason score ≥7 and 70 patients diagnosed with BPH were collected after digital rectal examination (DRE) of the prostate. miR expression profiles were determined using TaqMan Low Density Array experiments, and normalized Ct values for the miRs were compared between PCa and BPH groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether miR detection in urine is suitable for distinguishing patients with PCa from those with BPH. The identified miR‑100/200b signature was significantly correlated with PCa. Using a multivariable logistic regression approach, a base model including the clinical variables age, prostate‑specific antigen (PSA), the percentage of free PSA and DRE was generated, and a second base model additionally contained the miR‑100/200b signature. ROC analysis demonstrated that the combined model significantly outperformed the capacity of PSA (P<0.001) and the base model (P=0.01) to discriminate between PCa and BPH patients. In terms of evaluation of the sub‑group of patients in the gray zone of PSA levels, the performance of the combined model for predicting PCa cases was significantly superior to PSA level determination (P<0.001) and the base model (P=0.009). In addition, decision curve analysis demonstrated that the

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

    SciTech Connect

    Spratt, Daniel E.; Pei, Xin; Yamada, Josh; Kollmeier, Marisa A.; Cox, Brett; Zelefsky, Michael J.

    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-, 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

  15. Quantitative Proteomic Profiling of Prostate Cancer Reveals a Role for miR-128 in Prostate Cancer*

    PubMed Central

    Khan, Amjad P.; Poisson, Laila M.; Bhat, Vadiraja B.; Fermin, Damian; Zhao, Rong; Kalyana-Sundaram, Shanker; Michailidis, George; Nesvizhskii, Alexey I.; Omenn, Gilbert S.; Chinnaiyan, Arul M.; Sreekumar, Arun

    2010-01-01

    Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of biomarkers of cancer invasion and disease aggressiveness. Although alterations in gene expression have been extensively quantified during neoplastic progression, complementary analyses of proteomic changes have been limited. Here we interrogate the proteomic alterations in a cohort of 15 prostate-derived tissues that included five each from adjacent benign prostate, clinically localized prostate cancer, and metastatic disease from distant sites. The experimental strategy couples isobaric tags for relative and absolute quantitation with multidimensional liquid phase peptide fractionation followed by tandem mass spectrometry. Over 1000 proteins were quantified across the specimens and delineated into clinically localized and metastatic prostate cancer-specific signatures. Included in these class-specific profiles were both proteins that were known to be dysregulated during prostate cancer progression and new ones defined by this study. Enrichment analysis of the prostate cancer-specific proteomic signature, to gain insight into the functional consequences of these alterations, revealed involvement of miR-128-a/b regulation during prostate cancer progression. This finding was validated using real time PCR analysis for microRNA transcript levels in an independent set of 15 clinical specimens. miR-128 levels were elevated in benign prostate epithelial cell lines compared with invasive prostate cancer cells. Knockdown of miR-128 induced invasion in benign prostate epithelial cells, whereas its overexpression attenuated invasion in prostate cancer cells. Taken together, our profiles of the proteomic alterations of prostate cancer progression revealed miR-128 as a potentially important negative regulator of prostate cancer cell invasion. PMID:19955085

  16. Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Localization of Recurrent Prostate Cancer After External Beam Radiotherapy

    SciTech Connect

    Haider, Masoom A. Chung, Peter; Sweet, Joan; Toi, Ants; Jhaveri, Kartik; Menard, Cynthia; Warde, Padraig; Trachtenberg, John; Lockwood, Gina M.Math.; Milosevic, Michael

    2008-02-01

    Purpose: To compare the performance of T2-weighted (T2w) imaging and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of the prostate gland in the localization of recurrent prostate cancer in patients with biochemical failure after external beam radiotherapy (EBRT). Methods and Materials: T2-weighted imaging and DCE MRI were performed in 33 patients with suspected relapse after EBRT. Dynamic contrast-enhanced MRI was performed with a temporal resolution of 95 s. Voxels enhancing at 46 s after injection to a greater degree than the mean signal intensity of the prostate at 618 s were considered malignant. Results from MRI were correlated with biopsies from six regions in the peripheral zone (PZ) (base, mid, and apex). The percentage of biopsy core positive for malignancy from each region was correlated with the maximum diameter of the tumor on DCE MRI with a linear regression model. Results: On a sextant basis, DCE MRI had significantly better sensitivity (72% [21of 29] vs. 38% [11 of 29]), positive predictive value (46% [21 of 46] vs. 24% [11 of 45]) and negative predictive value (95% [144 of 152] vs. 88% [135 of 153] than T2w imaging. Specificities were high for both DCE MRI and T2w imaging (85% [144 of 169] vs. 80% [135 of 169]). There was a linear relationship between tumor diameters on DCE MRI and the percentage of cancer tissue in the corresponding biopsy core (r = 0.9, p < 0.001), with a slope of 1.2. Conclusions: Dynamic contrast-enhanced MRI performs better than T2w imaging in the detection and localization of prostate cancer in the peripheral zone after EBRT. This may be helpful in the planning of salvage therapy.

  17. SU-F-19A-11: Retrospective Evaluation of Thermal Coverage by Thermobrachytherapy Seed Arrangements of Clinical LDR Prostate Implants

    SciTech Connect

    Warrell, G; Shvydka, D; Chen, C; Parsai, E

    2014-06-15

    Purpose: The superiority of a properly-administered combination of radiation therapy and hyperthermia over radiation alone in treatment of human cancers has been demonstrated in multiple studies examining radiobiology, local control, and survival. Unfortunately, hyperthermia is not yet a common modality in oncology practice, due in part to the technical difficulty of heating a deep-seated target volume to sufficient temperature. To address this problem, our group has invented a thermobrachytherapy (TB) seed based on a commonly-used low dose-rate permanent brachytherapy seed for implant in solid tumors. Instead of the tungsten radiographic marker of the standard seed, the TB seed contains one of a self-regulating ferromagnetic alloy. Placement of a patient implanted with such seeds in an oscillating magnetic field generates heat via induction of eddy currents. We present the results of studies of the capability of clinically-realistic TB seed arrangements to adequately heat defined target volumes. Methods: Seed distributions for several past LDR prostate permanent implant brachytherapy patients were reproduced in the finite element analysis software package COMSOL Multiphysics 4.4, with the difference that TB seeds were modelled, rather than the radiation-only seeds actually used for their treatments. The implant geometries were mainly of the modified peripheral loading type; a range of prostatic volumes and blood perfusion rates likely to be seen in a clinical setting were examined. Results: According to the simulations, when distributed to optimize radiation dose, TB seeds also produce sufficient heat to provide thermal coverage of the target given proper selection of the magnetic field strength. However, the thermal distributions may be improved by additional use of hyperthermia-only seeds. Conclusion: A dual-modality seed intended as an alternative to and using the same implantation apparatus and technique as the standard LDR permanent implant seed has been

  18. Prospective evaluation of quality of life after interstitial brachytherapy for localized prostate cancer

    SciTech Connect

    Caffo, Orazio . E-mail: orazio.caffo@apss.tn.it; Fellin, Gianni; Bolner, Andrea; Coccarelli, Franco; Divan, Claudio; Frisinghelli, Michela; Mussari, Salvatore; Ziglio, Franco; Malossini, Gianni; Tomio, Luigi; Galligioni, Enzo

    2006-09-01

    Purpose: Permanent interstitial brachytherapy (IB) has become an increasingly appealing therapeutic option for localized prostate cancer (LPC) among physicians and patients because it involves short hospitalization and treatment and its postulated low degree of toxicity may reduce its impact on the patients' quality of life (QoL). The aim of this prospective study was to assess the impact of IB on the QoL of patients with LPC. Methods and Materials: A validated self-completed questionnaire was administered to the patients before and after IB and then at yearly intervals. The items allowed the identification of seven subscales exploring physical well-being (PHY), physical autonomy (POW), psychological well-being (PSY), relational life (REL), urinary function (URI), rectal function (REC), and sexual function (SEX). Results: The assessment of the QoL of 147 patients treated between May 2000 and February 2005 revealed no relevant differences in the PHY scale scores 1 month after IB or later, and the same was true of the POW, PSY, and REL scales. Urinary function significantly worsened after IB and returned to pretreatment levels only after 3 years; the impact of the treatment on the URI scale was greater in the patients with good baseline urinary function than in those presenting more urinary symptoms before IB. Rectal and sexual functions were significantly worse only at the post-IB evaluation. Conclusions: The results of the present study confirm that the impact of IB on the patients' QoL is low despite its transient negative effects on some function, and extend existing knowledge concerning QoL after IB.

  19. Differential expression of 5-alpha reductase isozymes in the prostate and its clinical implications

    PubMed Central

    Wang, Kai; Fan, Dong-Dong; Jin, Song; Xing, Nian-Zeng; Niu, Yi-Nong

    2014-01-01

    The development of human benign or malignant prostatic diseases is closely associated with androgens, primarily testosterone (T) and dihydrotestosterone (DHT). T is converted to DHT by 5-alpha reductase (5-AR) isozymes. Differential expression of 5-AR isozymes is observed in both human benign and malignant prostatic tissues. 5-AR inhibitors (5-ARI) are commonly used for the treatment of benign prostatic hyperplasia (BPH) and were once promoted as chemopreventive agents for prostate cancer (PCa). This review discusses the role of the differential expression of 5-AR in the normal development of the human prostate and in the pathogenesis and progression of BPH and PCa. PMID:24457841

  20. Massive Bleeding as the First Clinical Manifestation of Metastatic Prostate Cancer due to Disseminated Intravascular Coagulation with Enhanced Fibrinolysis

    PubMed Central

    Lopes, João Madeira; Victorino, Rui M. M.; Meneses Santos, João

    2016-01-01

    Disseminated intravascular coagulation (DIC) is the most frequent coagulation disorder associated with metastatic prostate adenocarcinoma. However, DIC with enhanced fibrinolysis as an initial presentation of prostate cancer is extremely rare. The appropriate treatment to control bleeding in these situations is challenging, controversial, and based on isolated case reports in the literature. A 66-year-old male presented at the emergency department with acute severe spontaneous ecchymoses localized to the limbs, laterocervical hematoma, and hemothorax. Prostate specific antigen level was 385 μg/L, bone scintigraphy revealed multiple bone metastases, and prostate biopsy confirmed adenocarcinoma (Gleason 9; 4 + 5). Laboratory investigation showed a pattern of enhanced fibrinolysis rather than the more common intravascular coagulation mechanism. Epsilon aminocaproic acid in monotherapy was initiated with a clear and rapid control of bleeding manifestations. This rare case of massive bleeding due to DIC with enhanced fibrinolysis as the first manifestation of prostate cancer suggests that in selected cases where the acute bleeding dyscrasia is clearly associated with a dominant fibrinolysis mechanism it is possible to use an approach of monotherapy with antifibrinolytics. PMID:27803823

  1. Prostate MRI can reduce overdiagnosis and overtreatment of prostate cancer.

    PubMed

    Rosenkrantz, Andrew B; Taneja, Samir S

    2015-08-01

    The contemporary management of prostate cancer (PCa) has been criticized as fostering overdetection and overtreatment of indolent disease. In particular, the historical inability to identify those men with an elevated PSA who truly warrant biopsy, and, for those needing biopsy, to localize aggressive tumors within the prostate, has contributed to suboptimal diagnosis and treatment strategies. This article describes how modern multi-parametric MRI of the prostate addresses such challenges and reduces both overdiagnosis and overtreatment. The central role of diffusion-weighted imaging (DWI) in contributing to MRI's current impact is described. Prostate MRI incorporating DWI achieves higher sensitivity than standard systematic biopsy for intermediate-to-high risk tumor, while having lower sensitivity for low-grade tumors that are unlikely to impact longevity. Particular applications of prostate MRI that are explored include selection of a subset of men with clinical suspicion of PCa to undergo biopsy as well as reliable confirmation of only low-risk disease in active surveillance patients. Various challenges to redefining the standard of care to incorporate solely MRI-targeted cores, without concomitant standard systematic cores, are identified. These include needs for further technical optimization of current systems for performing MRI-targeted biopsies, enhanced education and expertise in prostate MRI among radiologists, greater standardization in prostate MRI reporting across centers, and recognition of the roles of pre-biopsy MRI and MRI-targeted biopsy by payers. Ultimately, it is hoped that the medical community in the United States will embrace prostate MRI and MRI-targeted biopsy, allowing all patients with known or suspected prostate cancer to benefit from this approach.

  2. An examination of clinical differences between carriers and non-carriers of chromosome 8q24 risk alleles in a New Zealand Caucasian population with prostate cancer

    PubMed Central

    Han, Dug Yeo; Karunasinghe, Nishi; Goudie, Megan; Masters, Jonathan G.; Ferguson, Lynnette R.

    2016-01-01

    Background. Prostate cancer makes up approximately 15% of all cancers diagnosed in men in developed nations and approximately 4% of cases in developing nations. Although it is clear that prostate cancer has a genetic component and single nucleotide polymorphisms (SNPs) can contribute to prostate cancer risk, detecting associations is difficult in multi-factorial diseases, as environmental and lifestyle factors also play a role. In this study, specific clinical characteristics, environmental factors and genetic risk factors were assessed for interaction with prostate cancer. Methods. A total of 489 prostate cancer cases and 427 healthy controls were genotyped for SNPs found on chromosome 8q24 and a genetic risk score was calculated. In addition the SNPs were tested for an association with a number of clinical and environmental factors. Results. Age and tobacco use were positively associated, whilst alcohol consumption was negatively associated with prostate cancer risk. The following SNPs found on chromosome 8q24 were statistically significantly associated with prostate cancer: rs10086908, rs16901979; rs1447295and rs4242382. No association between Gleason score and smoking status, or between Gleason score and genotype were detected. Conclusion. A genetic risk score was calculated based on the 15 SNPs tested and found to be significantly associated with prostate cancer risk. Smoking significantly contributed to the risk of developing prostate cancer, and this risk was further increased by the presence of four SNPs in the 8q24 chromosomal region. PMID:26966665

  3. DNA alterations in the tumor genome and their associations with clinical outcome in prostate cancer

    PubMed Central

    Liu, Wennuan

    2016-01-01

    Although most prostate cancer (PCa) cases are not life-threatening, approximately 293 000 men worldwide die annually due to PCa. These lethal cases are thought to be caused by coordinated genomic alterations that accumulate over time. Recent genome-wide analyses of DNA from subjects with PCa have revealed most, if not all, genetic changes in both germline and PCa tumor genomes. In this article, I first review the major, somatically acquired genomic characteristics of various subtypes of PCa. I then recap key findings on the relationships between genomic alterations and clinical parameters, such as biochemical recurrence or clinical relapse, metastasis and cancer-specific mortality. Finally, I outline the need for, and challenges with, validation of recent findings in prospective studies for clinical utility. It is clearer now than ever before that the landscape of somatically acquired aberrations in PCa is highlighted by DNA copy number alterations (CNAs) and TMPRSS2-ERG fusion derived from complex rearrangements, numerous single nucleotide variations or mutations, tremendous heterogeneity, and continuously punctuated evolution. Genome-wide CNAs, PTEN loss, MYC gain in primary tumors, and TP53 loss/mutation and AR amplification/mutation in advanced metastatic PCa have consistently been associated with worse cancer prognosis. With this recently gained knowledge, it is now an opportune time to develop DNA-based tests that provide more accurate patient stratification for prediction of clinical outcome, which will ultimately lead to more personalized cancer care than is possible at present. PMID:26975494

  4. Early clinical experience of radiotherapy of prostate cancer with volumetric modulated arc therapy

    PubMed Central

    2010-01-01

    Background To report about initial clinical experience in radiation treatment of carcinoma of prostate with volumetric modulated arcs with the RapidArc (RA) technology. Methods Forty-five patients with a median age of 72 ± 3, affected by prostate carcinoma (T1c: 22 patients, T2a-b: 17 patients, T3a-b: 6 patients. N0: 43 patients, N1-Nx: 2 patients, all M0), with initial PSA of 10.0 ± 3.0 ng/mL, were treated with RapidArc in a feasibility study. All patients were treated with single arc using 6MV photons. Dose prescription ranged between 76 (7 patients) and 78 Gy (38 patients) in 2Gy/fraction. Plan quality was assessed by means of Dose Volume Histogram (DVH) analysis. Technical parameters of arcs and pre-treatment quality assurance results (Gamma Agreement Index, GAI) are reported to describe delivery features. Early toxicity was scored (according to the Common Terminology Criteria of Adverse Effects scale, CTCAE, scale) at the end of treatment together with biochemical outcome (PSA). Results From DVH data, target coverage was fulfilling planning objectives: V95% was in average higher than 98% and V107%~0.0% (D2%~104.0% in average). Homogeneity D5%-D95% ranged between 6.2 ± 1.0% to 6.7 ± 1.3%. For rectum, all planning objectives were largely met (e.g. V70Gy = 10.7 ± 5.5% against an objective of < 25%) similarly for bladder (e.g. D2% = 79.4 ± 1.2Gy against an objective of 80.0Gy). Maximum dose to femurs was D2% = 36.7 ± 5.4Gy against an objective of 47Gy. Monitor Units resulted: MU/Gy = 239 ± 37. Average beam on time was 1.24 ± 0.0 minutes. Pre-treatment GAI resulted in 98.1 ± 1.1%. Clinical data were recorded as PSA at 6 weeks after RT, with median values of 0.4 ± 0.4 ng/mL. Concerning acute toxicity, no patient showed grade 2-3 rectal toxicity; 5/42 (12%) patients experienced grade 2 dysuria; 18/41 (44%) patients preserved complete or partial erectile function. Conclusion RapidArc proved to be a safe, qualitative and advantageous treatment modality for

  5. Combined AKT and MEK Pathway Blockade in Pre-Clinical Models of Enzalutamide-Resistant Prostate Cancer

    PubMed Central

    Toren, Paul; Kim, Soojin; Johnson, Fraser; Zoubeidi, Amina

    2016-01-01

    Despite recent improvements in patient outcomes using newer androgen receptor (AR) pathway inhibitors, treatment resistance in castrate resistant prostate cancer (CRPC) continues to remain a clinical problem. Co-targeting alternate resistance pathways are of significant interest to treat CRPC and delay the onset of resistance. Both the AKT and MEK signaling pathways become activated as prostate cancer develops resistance to AR-targeted therapies. This pre-clinical study explores co-targeting these pathways in AR-positive prostate cancer models. Using various in vitro models of prostate cancer disease states including androgen dependent (LNCaP), CRPC (V16D and 22RV1) and ENZ-resistant prostate cancer (MR49C and MR49F), we evaluate the relevance of targeting both AKT and MEK pathways. Our data reveal that AKT inhibition induces apoptosis and inhibits cell growth in PTEN null cell lines independently of their sensitivity to hormone therapy; however, AKT inhibition had no effect on the PTEN positive 22RV1 cell line. Interestingly, we found that MEK inhibition had greater effect on 22RV1 cells compared to LNCaP, V16D or ENZ-resistant cells MR49C and MR49F cells. In vitro, combination AKT and MEK blockade had evidence of synergy observed in some cell lines and assays, but this was not consistent across all results. In vivo, the combination of AKT and MEK inhibition resulted in more consistent tumor growth inhibition of MR49F xenografts and longer disease specific survival compared to AKT inhibitor monotherapy. As in our in vitro study, 22RV1 xenografts were more resistant to AKT inhibition while they were more sensitive to MEK inhibition. Our results suggest that targeting AKT and MEK in combination may be a valuable strategy in prostate cancer when both pathways are activated and further support the importance of characterizing the dominant oncogenic pathway in each patient’s tumor in order to select optimal therapy. PMID:27046225

  6. Combined AKT and MEK Pathway Blockade in Pre-Clinical Models of Enzalutamide-Resistant Prostate Cancer.

    PubMed

    Toren, Paul; Kim, Soojin; Johnson, Fraser; Zoubeidi, Amina

    2016-01-01

    Despite recent improvements in patient outcomes using newer androgen receptor (AR) pathway inhibitors, treatment resistance in castrate resistant prostate cancer (CRPC) continues to remain a clinical problem. Co-targeting alternate resistance pathways are of significant interest to treat CRPC and delay the onset of resistance. Both the AKT and MEK signaling pathways become activated as prostate cancer develops resistance to AR-targeted therapies. This pre-clinical study explores co-targeting these pathways in AR-positive prostate cancer models. Using various in vitro models of prostate cancer disease states including androgen dependent (LNCaP), CRPC (V16D and 22RV1) and ENZ-resistant prostate cancer (MR49C and MR49F), we evaluate the relevance of targeting both AKT and MEK pathways. Our data reveal that AKT inhibition induces apoptosis and inhibits cell growth in PTEN null cell lines independently of their sensitivity to hormone therapy; however, AKT inhibition had no effect on the PTEN positive 22RV1 cell line. Interestingly, we found that MEK inhibition had greater effect on 22RV1 cells compared to LNCaP, V16D or ENZ-resistant cells MR49C and MR49F cells. In vitro, combination AKT and MEK blockade had evidence of synergy observed in some cell lines and assays, but this was not consistent across all results. In vivo, the combination of AKT and MEK inhibition resulted in more consistent tumor growth inhibition of MR49F xenografts and longer disease specific survival compared to AKT inhibitor monotherapy. As in our in vitro study, 22RV1 xenografts were more resistant to AKT inhibition while they were more sensitive to MEK inhibition. Our results suggest that targeting AKT and MEK in combination may be a valuable strategy in prostate cancer when both pathways are activated and further support the importance of characterizing the dominant oncogenic pathway in each patient's tumor in order to select optimal therapy.

  7. Integrated clinical, whole-genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer

    PubMed Central

    Bova, G. Steven; Kallio, Heini M.L.; Annala, Matti; Kivinummi, Kati; Högnäs, Gunilla; Häyrynen, Sergei; Rantapero, Tommi; Kivinen, Virpi; Isaacs, William B.; Tolonen, Teemu; Nykter, Matti; Visakorpi, Tapio

    2016-01-01

    We report the first combined analysis of whole-genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21). Whole-genome and transcriptome sequence was obtained from nine anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 yr before death. Transcriptome analysis revealed increased expression of androgen receptor (AR)-regulated genes in liver metastases that harbored an AR p.L702H mutation, suggesting a dominant effect by the mutation despite being present in only one of an estimated 16 copies per cell. The metastases harbored several alterations to the PI3K/AKT pathway, including a clonal truncal mutation in PIK3CG and present in all metastatic sites studied. The list of truncal genomic alterations shared by all metastases included homozygous deletion of TP53, hemizygous deletion of RB1 and CHD1, and amplification of FGFR1. If the patient were treated today, given this knowledge, the use of second-generation androgen-directed therapies, cessation of glucocorticoid administration, and therapeutic inhibition of the PI3K/AKT pathway or FGFR1 receptor could provide personalized benefit. Three previously unreported truncal clonal missense mutations (ABCC4 p.R891L, ALDH9A1 p.W89R, and ASNA1 p.P75R) were expressed at the RNA level and assessed as druggable. The truncal status of mutations may be critical for effective actionability and merit further study. Our findings suggest that a large set of deeply analyzed cases could serve as a powerful guide to more effective prostate cancer basic science and personalized cancer medicine clinical trials. PMID:27148588

  8. Integrated clinical, whole-genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer.

    PubMed

    Bova, G Steven; Kallio, Heini M L; Annala, Matti; Kivinummi, Kati; Högnäs, Gunilla; Häyrynen, Sergei; Rantapero, Tommi; Kivinen, Virpi; Isaacs, William B; Tolonen, Teemu; Nykter, Matti; Visakorpi, Tapio

    2016-05-01

    We report the first combined analysis of whole-genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21). Whole-genome and transcriptome sequence was obtained from nine anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 yr before death. Transcriptome analysis revealed increased expression of androgen receptor (AR)-regulated genes in liver metastases that harbored an AR p.L702H mutation, suggesting a dominant effect by the mutation despite being present in only one of an estimated 16 copies per cell. The metastases harbored several alterations to the PI3K/AKT pathway, including a clonal truncal mutation in PIK3CG and present in all metastatic sites studied. The list of truncal genomic alterations shared by all metastases included homozygous deletion of TP53, hemizygous deletion of RB1 and CHD1, and amplification of FGFR1. If the patient were treated today, given this knowledge, the use of second-generation androgen-directed therapies, cessation of glucocorticoid administration, and therapeutic inhibition of the PI3K/AKT pathway or FGFR1 receptor could provide personalized benefit. Three previously unreported truncal clonal missense mutations (ABCC4 p.R891L, ALDH9A1 p.W89R, and ASNA1 p.P75R) were expressed at the RNA level and assessed as druggable. The truncal status of mutations may be critical for effective actionability and merit further study. Our findings suggest that a large set of deeply analyzed cases could serve as a powerful guide to more effective prostate cancer basic science and personalized cancer medicine clinical trials. PMID:27148588

  9. DNA Methylation-Guided Prediction of Clinical Failure in High-Risk Prostate Cancer

    PubMed Central

    Joniau, Steven; Lerut, Evelyne; Laenen, Annouschka; Gevaert, Thomas; Gevaert, Olivier; Spahn, Martin; Kneitz, Burkhard; Gramme, Pierre; Helleputte, Thibault; Isebaert, Sofie; Haustermans, Karin; Bollen, Mathieu

    2015-01-01

    Background Prostate cancer (PCa) is a very heterogeneous disease with respect to clinical outcome. This study explored differential DNA methylation in a priori selected genes to diagnose PCa and predict clinical failure (CF) in high-risk patients. Methods A quantitative multiplex, methylation-specific PCR assay was developed to assess promoter methylation of the APC, CCND2, GSTP1, PTGS2 and RARB genes in formalin-fixed, paraffin-embedded tissue samples from 42 patients with benign prostatic hyperplasia and radical prostatectomy specimens of patients with high-risk PCa, encompassing training and validation cohorts of 147 and 71 patients, respectively. Log-rank tests, univariate and multivariate Cox models were used to investigate the prognostic value of the DNA methylation. Results Hypermethylation of APC, CCND2, GSTP1, PTGS2 and RARB was highly cancer-specific. However, only GSTP1 methylation was significantly associated with CF in both independent high-risk PCa cohorts. Importantly, trichotomization into low, moderate and high GSTP1 methylation level subgroups was highly predictive for CF. Patients with either a low or high GSTP1 methylation level, as compared to the moderate methylation groups, were at a higher risk for CF in both the training (Hazard ratio [HR], 3.65; 95% CI, 1.65 to 8.07) and validation sets (HR, 4.27; 95% CI, 1.03 to 17.72) as well as in the combined cohort (HR, 2.74; 95% CI, 1.42 to 5.27) in multivariate analysis. Conclusions Classification of primary high-risk tumors into three subtypes based on DNA methylation can be combined with clinico-pathological parameters for a more informative risk-stratification of these PCa patients. PMID:26086362

  10. Ultrasound-Guided Transrectal Implantation of Gold Markers for Prostate Localization During External Beam Radiotherapy: Complication Rate and Risk Factors

    SciTech Connect

    Langenhuijsen, Johan F.; Lin, Emile N.J.T. van Kiemeney, Lambertus A.; Vight, Lisette P. van der; McColl, Gill; Visser, Andries G.; Witjes, J. Alfred

    2007-11-01

    Purpose: To report the complication rate and risk factors of transrectally implanted gold markers, used for prostate position verification and correction procedures. Methods and Materials: In 209 consecutive men with localized prostate cancer, four gold markers (1 x 7 mm) were inserted under ultrasound guidance in an outpatient setting, and the toxicity was analyzed. All patients received a questionnaire regarding complications after marker implantation. The complications and risk factors were further evaluated by reviewing the medical charts. Results: Of the 209 men, 13 (6.2%) had a moderate complication, consisting of pain and fever that resolved after treatment with oral medication. In 1.9% of the men, minor voiding complaints were observed. Other minor transient complications, defined as hematuria lasting >3 days, hematospermia, and rectal bleeding, occurred in 3.8%, 18.5%, and 9.1% of the patients, respectively. These complications were seen more often in patients with advanced tumor stage, younger age, and shorter duration of hormonal therapy. Conclusion: Transrectal gold marker implantation for high-precision prostate radiotherapy is a safe and well-tolerated procedure.

  11. Is whole gland salvage cryotherapy effective as palliative treatment of haematuria in patients with locally advanced prostate cancer? Results of a preliminary case series

    PubMed Central

    Mucciardi, Giuseppe; Galì, Alessandro; Pappalardo, Rosa; Lembo, Francesco; Anastasi, Giuseppina; Butticè, Salvatore; Ascenti, Giorgio; Lugnani, Franco

    2015-01-01

    Objectives: Locally advanced prostate cancer may cause several complications such as haematuria, bladder outlet obstruction, and renal failure due to the ureteral obstruction. Various treatments have been suggested, including radiotherapy, antifibrinolytics, bladder irrigation with alum solution, transurethral surgery and angioembolization, none of which have proven effectiveness. In the last years cryoablation has become a valid therapeutic option for prostate cancer. In our experience we used this ‘new’ technique as haemostatic therapy. Methods: We selected four patients with gross haematuria affected by locally advanced hormone refractory prostate cancer, who had already been treated with primary radiotherapy. We used third-generation cryotherapy: under ultrasonographic guidance, we inserted six cryoprobes, two in each of the vascular pedicles reaching at least −60°C, and three thermometers. We then induced two freeze–thaw cycles. Results: After the operation the haematuria stopped in all patients and at 9-month follow up we observed a mean of four red cells (range three to five) in the urinary sediment with no evidence of bacteriuria. Prostate volume, prostate-specific antigen and postmicturition residue were significantly reduced. Qmax improved significantly too. Conclusion: Our experience has given us good results with minimal intra- and postoperative complications. We think that haemostatic cryotherapy as a palliative approach for locally advanced prostate cancer could represent a valid treatment option and more consideration could be given to its use. PMID:26425138

  12. Clinical Outcome of Patients Treated With 3D Conformal Radiation Therapy (3D-CRT) for Prostate Cancer on RTOG 9406

    SciTech Connect

    Michalski, Jeff; Winter, Kathryn; Roach, Mack; Markoe, Arnold; Sandler, Howard M.; Ryu, Janice; Parliament, Matthew; Purdy, James A.; Valicenti, Richard K.; Cox, James D.

    2012-07-01

    Purpose: Report of clinical cancer control outcomes on Radiation Therapy Oncology Group (RTOG) 9406, a three-dimensional conformal radiation therapy (3D-CRT) dose escalation trial for localized adenocarcinoma of the prostate. Methods and Materials: RTOG 9406 is a Phase I/II multi-institutional dose escalation study of 3D-CRT for men with localized prostate cancer. Patients were registered on five sequential dose levels: 68.4 Gy, 73.8 Gy, 79.2 Gy, 74 Gy, and 78 Gy with 1.8 Gy/day (levels I-III) or 2.0 Gy/day (levels IV and V). Neoadjuvant hormone therapy (NHT) from 2 to 6 months was allowed. Protocol-specific, American Society for Therapeutic Radiation Oncology (ASTRO), and Phoenix biochemical failure definitions are reported. Results: Thirty-four institutions enrolled 1,084 patients and 1,051 patients are analyzable. Median follow-up for levels I, II, III, IV, and V was 11.7, 10.4, 11.8, 10.4, and 9.2 years, respectively. Thirty-six percent of patients received NHT. The 5-year overall survival was 90%, 87%, 88%, 89%, and 88% for dose levels I-V, respectively. The 5-year clinical disease-free survival (excluding protocol prostate-specific antigen definition) for levels I-V is 84%, 78%, 81%, 82%, and 82%, respectively. By ASTRO definition, the 5-year disease-free survivals were 57%, 59%, 52%, 64% and 75% (low risk); 46%, 52%, 54%, 56%, and 63% (intermediate risk); and 50%, 34%, 46%, 34%, and 61% (high risk) for levels I-V, respectively. By the Phoenix definition, the 5-year disease-free survivals were 68%, 73%, 67%, 84%, and 80% (low risk); 70%, 62%, 70%, 74%, and 69% (intermediate risk); and 42%, 62%, 68%, 54%, and 67% (high risk) for levels I-V, respectively. Conclusion: Dose-escalated 3D-CRT yields favorable outcomes for localized prostate cancer. This multi-institutional experience allows comparison to other experiences with modern radiation therapy.

  13. Calcifications Are Potential Surrogates for Prostate Localization in Image-Guided Radiotherapy

    SciTech Connect

    Zeng, Grace G. McGowan, Tom S.; Larsen, Tessa M.; Bruce, Lisa M.; Moran, Natasha K.; Tsao, Jonathan R.; MacPherson, Miller S.

    2008-11-15

    Purpose: To investigate the feasibility of using calcifications as surrogates for the prostate position during cone-beam computed tomography (CBCT) image-guided radiotherapy. Methods and Materials: The twice-weekly CBCT images taken during the treatment course of 4 patients were retrospectively studied for the stability of the calcifications. The geometric center of three fiducial markers was used as the reference. The planning CT images of 131 prostate patients recently treated with external beam radiotherapy at our center were reviewed to estimate the calcification occurrence rate. Analysis was conducted using the Varian Eclipse treatment planning system. Two patients were treated using prostate calcifications as the landmark in on-line registration. Both the Varian standard and the low-dose CBCT modes were used for imaging. Results: The calcifications were found to be stable during the treatment course. At the 95% confidence interval, the difference between the distance from an identified calcification to the fiducial markers on CBCT and the distance on the planning CT scans was 0.2 {+-} 2.0 mm, 0.8 {+-} 2.2 mm, and 0.4 {+-} 2.4 mm in the left-right, anteroposterior, and superoinferior direction, respectively. Of the 131 patients, 46 (35%) had well-defined calcifications either inside the prostate or near the borders. Our experience in treating the first 2 patients demonstrated that the calcifications are easily distinguished on low-dose scans and that calcification registration can be precisely performed. Conclusion: The results of our study have shown that calcifications can be reliable markers of prostate position and allow for precise image guidance with a low-imaging dose. With this approach, potentially about one-third of prostate patients could benefit from precise image guidance without the invasive use of markers.

  14. Time to failure after definitive therapy for prostate cancer: implications for importance of aggressive local treatment

    PubMed Central

    Taira, Al V.; Butler, Wayne M.; Galbreath, Robert W.; Fiano, Ryan; Wallner, Kent E.; Adamovich, Edward

    2013-01-01

    Purpose To explore patterns of time to failure in men receiving high doses of permanent seed brachytherapy with or without external beam radiation therapy as a function of risk status. Material and methods Two thousand two hundred and thirty four patients were treated with prostate brachytherapy with median follow up of 8.0 years. The population was 35% low risk, 49% intermediate risk, and 16% high risk (NCCN). Median day 0 implant D90 was 119% and V100 was 98%. Treatment failure was defined as PSA > 0.40 ng/mL after nadir. Rates of biochemical failure, distant metastases, and prostate cancer death were determined with non-prostate death as a competing risk. Results For all patients, the 10-year biochemical failure, distant metastases, and cause-specific mortality were 4.4%, 1.4%, and 1.3%, respectively. The biochemical failure rates were 1.3%, 4.8%, and 10.0% for men with low, intermediate, and high risk disease, respectively. Median time to failure was 2.8 years. In men who died from prostate cancer, the median time from treatment failure to death was 4.2 years. Overall, 83% of biochemical failures and 97% of metastases occurred within the first 4 years after treatment. Conclusions With the dose escalation achieved by high quality brachytherapy dosimetry, even high-risk prostate cancer patients have excellent long term biochemical outcomes. Treatment failures occur early, and one third become metastatic and progress rapidly to prostate cancer death. The low frequency and pattern of failures suggest the presence of micrometastatic disease prior to treatment is rare, even in high risk patients. PMID:24474970

  15. Comparison of Acute and Late Toxicities for Three Modern High-Dose Radiation Treatment Techniques for Localized Prostate Cancer

    SciTech Connect

    Mohammed, Nasiruddin; Kestin, Larry; Ghilezan, Mihai; Krauss, Daniel; Vicini, Frank; Brabbins, Donald; Gustafson, Gary; Ye Hong; Martinez, Alavaro

    2012-01-01

    Purpose: We compared acute and late genitourinary (GU) and gastrointestinal (GI) toxicities in prostate cancer patients treated with three different high-dose radiation techniques. Methods and Materials: A total of 1,903 patients with localized prostate cancer were treated with definitive RT at William Beaumont Hospital from 1992 to 2006: 22% with brachytherapy alone (BT), 55% with image-guided external beam (EB-IGRT), and 23% external beam with high-dose-rate brachytherapy boost (EBRT+HDR). Median dose with BT was 120 Gy for LDR and 38 Gy for HDR (9.5 Gy Multiplication-Sign 4). Median dose with EB-IGRT was 75.6 Gy (PTV) to prostate with or without seminal vesicles. For EBRT+HDR, the pelvis was treated to 46 Gy with an additional 19 Gy (9.5 Gy Multiplication-Sign 2) delivered via HDR. GI and GU toxicity was evaluated utilizing the NCI-CTC criteria (v.3.0). Median follow-up was 4.8 years. Results: The incidences of any acute {>=} Grade 2 GI or GU toxicities were 35%, 49%, and 55% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Any late GU toxicities {>=} Grade 2 were present in 22%, 21%, and 28% for BT, EB-IGRT, and EBRT+HDR (p = 0.01), respectively. Patients receiving EBRT+HDR had a higher incidence of urethral stricture and retention, whereas dysuria was most common in patients receiving BT. Any Grade {>=}2 late GI toxicities were 2%, 20%, and 9% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Differences were most pronounced for rectal bleeding, with 3-year rates of 0.9%, 20%, and 6% (p < 0.001) for BT, EB-IGRT, and EBRT+HDR respectively. Conclusions: Each of the three modern high-dose radiation techniques for localized prostate cancer offers a different toxicity profile. These data can help patients and physicians to make informed decisions regarding radiotherapy for prostate andenocarcinoma.

  16. Realtime TRUS/MRI Fusion Targeted-Biopsy for Prostate Cancer: A Clinical Demonstration of Increased Positive Biopsy Rates

    NASA Astrophysics Data System (ADS)

    Kadoury, Samuel; Yan, Pingkun; Xu, Sheng; Glossop, Neil; Choyke, Peter; Turkbey, Baris; Pinto, Peter; Wood, Bradford J.; Kruecker, Jochen

    In this paper, a system for fusion of realtime transrectal ultrasound (TRUS) with pre-acquired 3D images of the prostate is presented with a clinical demonstration on a cohort of 101 patients with suspicion of prostate cancer. Electromagnetically tracked biopsy guides for endocavity ultrasound transducers were calibrated and used to fuse MRI-based suspicious lesion locations with ultrasound image coordinates. The prostate shape is segmented from MRI in a semi-automated fashion via a model-based approach, and intraoperative image registration is performed between MR and ultrasound image space to superimpose target fiducials markers on the ultrasound image. In order to align both modalities, a surface model is automatically extracted from 2D swept TRUS images using a partial active shape model, utilizing image features and prior statistics. An automatic prostate motion compensation algorithm can be triggered as needed. The results were used to display live TRUS images fused with spatially corresponding realtime multiplanar reconstructions (MPRs) of the MR image volume. In this study, all patients were scanned with 3T MRI and TRUS for biopsy. Clinical results show significant improvement of target visualization and of positive detection rates during TRUS-guided biopsies. It also demonstrates the feasibility of realtime MR/TRUS image fusion for out-of-gantry procedures.

  17. Local Control Following Permanent Prostate Brachytherapy: Effect of High Biologically Effective Dose on Biopsy Results and Oncologic Outcomes

    SciTech Connect

    Stone, Nelson N.; Stock, Richard G.; Cesaretti, Jamie A.; Unger, Pam

    2010-02-01

    Purpose: To determine factors that influence local control and systemic relapse in patients undergoing permanent prostate brachytherapy (PPB). Methods and Materials: A total of 584 patients receiving PPB alone or PPB with external beam radiation therapy (19.5%) agreed to undergo prostate biopsy (PB) at 2 years postimplantion and yearly if results were positive or if the prostate-specific antigen (PSA) level increased. Short-term hormone therapy was used with 280 (47.9%) patients. Radiation doses were converted to biologically effective doses (BED) (using alpha/beta = 2). Comparisons were made by chi-square analysis and linear regression. Survival was determined by the Kaplan-Meier method. Results: The median PSA concentration was 7.1 ng/ml, and the median follow-up period was 7.1 years. PB results were positive for 48/584 (8.2%) patients. Positive biopsy results by BED group were as follows: 22/121 (18.2%) patients received a BED of <=150 Gy; 15/244 (6.1%) patients received >150 to 200 Gy; and 6/193 (3.1%; p < 0.001) patients received >200 Gy. Significant associations of positive PB results by risk group were low-risk group BED (p = 0.019), intermediate-risk group hormone therapy (p = 0.011) and BED (p = 0.040), and high-risk group BED (p = 0.004). Biochemical freedom from failure rate at 7 years was 82.7%. Biochemical freedom from failure rate by PB result was 84.7% for negative results vs. 59.2% for positive results (p < 0.001). Cox regression analysis revealed significant associations with BED (p = 0.038) and PB results (p = 0.002) in low-risk patients, with BED (p = 0.003) in intermediate-risk patients, and with Gleason score (p = 0.006), PSA level (p < 0.001), and PB result (p = 0.038) in high-risk patients. Fifty-three (9.1%) patients died, of which eight deaths were due to prostate cancer. Cause-specific survival was 99.2% for negative PB results vs. 87.6% for positive PB results (p < 0.001). Conclusions: Higher radiation doses are required to achieve local

  18. The clinical role of multimodality imaging in the detection of prostate cancer recurrence after radical prostatectomy and radiation therapy: past, present, and future

    PubMed Central

    Paparo, Francesco; Massollo, Michela; Rollandi, Ludovica; Piccardo, Arnoldo; Ruggieri, Filippo Grillo; Rollandi, Gian Andrea

    2015-01-01

    Detection of the recurrence sites in prostate cancer (PCa) patients affected by biochemical recurrence after radical prostatectomy (RP) and radiation therapy (RT) is still a challenge for clinicians, nuclear medicine physicians, and radiologists. In the era of personalised and precision care, this task requires the integration, amalgamation, and combined analysis of clinical and imaging data from multiple sources. At present, multiparametric Magnetic Resonance Imaging (mpMRI) and choline–positron emission tomography (PET) are giving encouraging results; their combination allows the effective detection of local, lymph nodal, and skeletal recurrences at low PSA levels. Future diagnostic perspectives include the clinical implementation of PET/MRI scanners, multimodal fusion imaging platforms for retrospective co-registration of PET and MR images, real-time transrectal ultrasound/mpMRI fusion imaging, and novel organ-specific PET radiotracers. PMID:26435743

  19. [The effect of prostatilen on the hemostatic indices in chronic prostatitis (a clinical and experimental study)].

    PubMed

    al-Shukri, S Kh; Petrishchev, N N; Gorbachev, A G; Mikhaĭlova, I A; Bobkov, Iu A; Kuz'min, I V; Borovets, S Iu; Savel'eva, I B; Korokhodkina, M V

    1997-01-01

    Prostatilen effects on hemostasis were studied in 120 intact and 240 chronic prostatitis rats, 34 patients with chronic prostatitis. Intact rats responded to prostatilen by inhibition of platelet-vascular and coagulation hemostatic mechanisms and activation of fibrinolysis. Experimental chronic prostatitis in rats induced hemostatic shifts to hypercoagulation. These parameters returned to normal after 5- and 10-day course of prostatilen administration. A single prostatilen dose was unable to produce the above action. As to patients with chronic prostatitis, there were also prostatilen-induced platelet-vascular hemostatic normalization and fibrinolysis activation. Hemocoagulation was affected in a less degree. Prostatilen effects were unrelated to the disease stage. Normalization of hemostasis seems to be one of the factors of prostatilen therapeutic efficacy in chronic prostatitis. This peptide is found effective as a pathogenetic treatment of chronic prostatitis.

  20. Dosimetric Impact and Theoretical Clinical Benefits of Fiducial Markers for Dose Escalated Prostate Cancer Radiation Treatment

    SciTech Connect

    Gauthier, Isabelle Carrier, Jean-Francois; Beliveau-Nadeau, Dominic; Fortin, Bernard; Taussky, Daniel

    2009-07-15

    Purpose: To assess the impact of fiducial markers and daily kilovoltage imaging (FM-kV) on dose-volume histogram (DVH) parameters and normal tissue complication probabilities (NTCPs) for the rectum and bladder during prostate cancer radiotherapy. Methods and Materials: Two different setup scenarios were compared for 20 patients treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer to a total dose of 76 Gy: a traditional setup with planning target volume (PTV) margins associated with skin mark alignment vs. another setup using FM-kV. Various DVH parameters were compared, including Radiation Therapy Oncology Group (RTOG) dose-volume constraints for the rectum and bladder. Analysis of NTCPs was also performed according to the Lyman model. Results: With the traditional setup, 85% of patients had rectal V70{sub Gy} >25% compared with 45% with FM-kV. Moreover, 30% of patients with traditional setup vs. 5% with FM-kV did not fulfill at least 3 RTOG constraint parameters for the rectum. Mean rectal and bladder dose were 4.7 Gy and 6.7 Gy less, respectively, with FM-kV. The NTCP for the rectum was 11.5% with the traditional setup and 9% with FM-kV. This indicates that with FM-kV, the prescription dose could be increased by 2.1 Gy while keeping the same level of late rectal toxicity as with the traditional setup. Conclusions: Use of FM-kV is an efficient way of lowering the proportion of patients not fulfilling RTOG rectal and bladder dose-volume constraints. The results of the NTCP analysis suggest that the PTV margin reduction allowed by FM-kV should decrease the rate of late rectal toxicities or may allow moderate dose escalation.

  1. Evaluation of clinical margins via simulation of patient setup errors in prostate IMRT treatment plans

    SciTech Connect

    Gordon, J. J.; Crimaldi, A. J.; Hagan, M.; Moore, J.; Siebers, J. V.

    2007-01-15

    This work evaluates: (i) the size of random and systematic setup errors that can be absorbed by 5 mm clinical target volume (CTV) to planning target volume (PTV) margins in prostate intensity modulated radiation therapy (IMRT); (ii) agreement between simulation results and published margin recipes; and (iii) whether shifting contours with respect to a static dose distribution accurately predicts dose coverage due to setup errors. In 27 IMRT treatment plans created with 5 mm CTV-to-PTV margins, random setup errors with standard deviations (SDs) of 1.5, 3, 5 and 10 mm were simulated by fluence convolution. Systematic errors with identical SDs were simulated using two methods: (a) shifting the isocenter and recomputing dose (isocenter shift), and (b) shifting patient contours with respect to the static dose distribution (contour shift). Maximum tolerated setup errors were evaluated such that 90% of plans had target coverage equal to the planned PTV coverage. For coverage criteria consistent with published margin formulas, plans with 5 mm margins were found to absorb combined random and systematic SDs{approx_equal}3 mm. Published recipes require margins of 8-10 mm for 3 mm SDs. For the prostate IMRT cases presented here a 5 mm margin would suffice, indicating that published recipes may be pessimistic. We found significant errors in individual plan doses given by the contour shift method. However, dose population plots (DPPs) given by the contour shift method agreed with the isocenter shift method for all structures except the nodal CTV and small bowel. For the nodal CTV, contour shift DPP differences were due to the structure moving outside the patient. Small bowel DPP errors were an artifact of large relative differences at low doses. Estimating individual plan doses by shifting contours with respect to a static dose distribution is not recommended. However, approximating DPPs is acceptable, provided care is taken with structures such as the nodal CTV which lie close

  2. Implementing intensity modulated radiotherapy to the prostate bed: Dosimetric study and early clinical results

    SciTech Connect

    Riou, Olivier; Laliberté, Benoit; Azria, David; Menkarios, Cathy; Llacer Moscardo, Carmen; Dubois, Jean-Bernard; Aillères, Norbert; Fenoglietto, Pascal

    2013-07-01

    Salvage intensity modulated radiotherapy (IMRT) to the prostate bed has hardly been studied so far. We present here a feasibility study and early clinical results for 10 patients. These patients were selected on the basis of having either a biochemical relapse or high risk histology after prostatectomy. They were treated using “sliding-window” IMRT to 68 Gy in 34 fractions. Three-dimensional conformal radiotherapy (3D-CRT) plans were generated using the same planning computed tomography data set. Dose coverage of planning target volumes (PTVs) and of organs-at-risk (OAR, namely: rectum, bladder, and femoral heads) were compared. Acute toxicity and chronic toxicity were measured using the Common Toxicity Criteria for Adverse Events version 3.0 scale. IMRT significantly reduces the dose above the prescription dose given to the PTV1 (mean dose: IMRT 67.2 Gy vs 3D-CRT 67.7 Gy (p = 0.0137)), without altering dose coverage for PTV2 (mean dose: IMRT 68.1 Gy vs 3D-CRT 68.0 Gy (p = 0.3750)). Doses to OAR were lower with IMRT and differences were statistically significant (mean dose: IMRT 51.4 Gy vs 3D-CRT 56.6 Gy for rectum (p = 0.002), IMRT 45.1 Gy vs 3D-CRT 53.1 Gy for bladder (p = 0.002), and IMRT 26.1 Gy vs 3D-CRT 28.4 Gy for femoral heads (p = 0.0059)). There was no acute or chronic genitourinary or gastrointestinal toxicity >1 with a median follow-up of 38 months. IMRT to the prostatic fossa is feasible and reduces dose to OAR, with consequential limited toxicity.

  3. First Report: Robot-Assisted Total Pelvic Exenteration for Locally Advanced Prostate Cancer.

    PubMed

    Castillo, Octavio A; Vidal-Mora, Ivar; Rodriguez-Carlin, Arquimedes; Silva, Andres; Schatloff, Oscar

    2015-07-01

    Pelvic exenteration is used in the treatment of several pelvic cancers, including those of the rectum, uterus, and bladder. We report the first case of robotic pelvic exenteration for the treatment of symptomatic prostate cancer involving the rectum and bladder. A six-port transperitoneal robotic approach was used. Bilateral extended lymphadenectomy up to the inferior mesenteric artery was performed. The rectum and bladder were removed en bloc, and a double-barrel anastomosis was then performed with both ureters being connected to the lower opening of the colostomy. Operative time was 249 minutes, and estimated blood loss was 600 mL. No intraoperative or postoperative complications were recorded. Biopsy of the rectum and bladder showed prostatic adenocarcinoma with a Gleason score of 9 (5+4), and 1 of 17 nodes was positive for cancer. Postoperative prostate-specific antigen level was 1.24 ng/mL. The patient is already 19 months after surgery with optimal quality of life. Thus pelvic exenteration is a feasible alternative for highly symptomatic prostate cancer involving adjacent pelvic organs. PMID:26134069

  4. A Prospective Randomized Trial of Two Different Prostate Biopsy Schemes

    ClinicalTrials.gov

    2016-07-03

    Prostate Cancer; Local Anesthesia; Prostate-Specific Antigen/Blood; Biopsy/Methods; Image-guided Biopsy/Methods; Prostatic Neoplasms/Diagnosis; Prostate/Pathology; Prospective Studies; Humans; Male; Ultrasonography, Interventional/Methods

  5. Results and DVH analysis of late rectal bleeding in patients treated with 3D-CRT or IMRT for localized prostate cancer.

    PubMed

    Someya, Masanori; Hori, Masakazu; Tateoka, Kunihiko; Nakata, Kensei; Takagi, Masaru; Saito, Masato; Hirokawa, Naoki; Hareyama, Masato; Sakata, Koh-Ichi

    2015-01-01

    In patients undergoing radiotherapy for localized prostate cancer, dose-volume histograms and clinical variables were examined to search for correlations between radiation treatment planning parameters and late rectal bleeding. We analyzed 129 patients with localized prostate cancer who were managed from 2002 to 2010 at our institution. They were treated with 3D conformal radiation therapy (3D-CRT, 70 Gy/35 fractions, 55 patients) or intensity-modulated radiation therapy (IMRT, 76 Gy/38 fractions, 74 patients). All radiation treatment plans were retrospectively reconstructed, dose-volume histograms of the rectum were generated, and the doses delivered to the rectum were calculated. Time to rectal bleeding ranged from 9-53 months, with a median of 18.7 months. Of the 129 patients, 33 patients had Grade 1 bleeding and were treated with steroid suppositories, while 25 patients with Grade 2 bleeding received argon plasma laser coagulation therapy (APC). Three patients with Grade 3 bleeding required both APC and blood transfusion. The 5-year incidence rate of Grade 2 or 3 rectal bleeding was 21.8% for the 3D-CRT group and 21.6% for the IMRT group. Univariate analysis showed significant differences in the average values from V65 to V10 between Grades 0-1 and Grades 2-3. Multivariate analysis demonstrated that patients with V65 ≥ 17% had a significantly increased risk (P = 0.032) of Grade 2 or 3 rectal bleeding. Of the 28 patients of Grade 2 or 3 rectal bleeding, 17 patients (60.7%) were cured by a single session of APC, while the other 11 patients required two sessions. Thus, none of the patients had any further rectal bleeding after the second APC session.

  6. Clinically available RNA profiling tests of prostate tumors: utility and comparison

    PubMed Central

    Na, Rong; Wu, Yishuo; Ding, Qiang; Xu, Jianfeng

    2016-01-01

    In the postscreening era, physicians are in need of methods to discriminate aggressive from nonaggressive prostate cancer (PCa) to reduce overdiagnosis and overtreatment. However, studies have shown that prognoses (e.g., progression and mortality) differ even among individuals with similar clinical and pathological characteristics. Existing risk classifiers (TMN grading system, Gleason score, etc.) are not accurately enough to represent the biological features of PCa. Using new genomic technologies, novel biomarkers and classifiers have been developed and shown to add value to clinical or pathological risk factors for predicting aggressive disease. Among them, RNA testing (gene expression analysis) is useful because it can not only reflect genetic variations but also reflect epigenetic regulations. Commercially available RNA profiling tests (Oncotype Dx, Prolaris, and Decipher) have demonstrated strong abilities to discriminate PCa with poor prognosis from less aggressive diseases. For instance, these RNA profiling tests can predict disease progression in active surveillance patients or early recurrence after radical treatments. These tests may offer more dependable methods for PCa prognosis prediction to make more accurate and personal medical decisions. PMID:26975490

  7. Prostate Cancer in a Male with Holt-Oram Syndrome: First Clinical Association of the TBX5 Mutation

    PubMed Central

    Aherne, Noel J.

    2013-01-01

    Holt-Oram syndrome is an autosomal dominant disorder which is caused by mutations of TBX5 and is characterised by cardiac and skeletal abnormalities. TBX5 is part of the T-box gene family and is thought to upregulate tumour cell proliferation and metastasis when mutated. We report the first clinical case of prostate cancer in an individual with Holt Oram syndrome. PMID:23984174

  8. Feasibility of MR Imaging/MR Spectroscopy-Planned Focal Partial Salvage Permanent Prostate Implant (PPI) for Localized Recurrence After Initial PPI for Prostate Cancer

    SciTech Connect

    Hsu, Charles C.; Hsu, Howard; Pickett, Barby; Crehange, Gilles; Hsu, I-Chow Joe; Dea, Ryan; Weinberg, Vivian; Gottschalk, Alexander R.; Kurhanewicz, John; Shinohara, Katsuto; Roach, Mack

    2013-02-01

    Purpose: To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy-proven local recurrence after initial PPI without evidence of distant disease. Methods and Materials: From 2003-2009, 15 patients underwent MRI/magnetic resonance spectroscopy (MRS) planning for salvage brachytherapy (psPPI, I-125 [n=14; 144 Gy]; Pd-103 [n=1; 125 Gy]) without hormone therapy. Full dose was prescribed to areas of recurrence and underdosage, without entire prostate implantation. Limiting urethral and rectal toxicity was prioritized. Follow-up was from salvage date to prostate-specific antigen (PSA) concentration failure (Phoenix criteria = nadir + 2.0; ASTRO = 3 consecutive rises), recurrence, distant metastases, or last follow-up PSA level. Progression-free survival (PFS) was defined as no PSA failure or biopsy-proven recurrence without all-cause mortality. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Results: At salvage, median age was 68 years, and PSA concentration was 3.5 ng/mL (range, 0.9-5.6 ng/mL). Abnormal MRI/MRS findings were evident in 40% of patients. Biopsy-proven recurrences consisted of a single focus (80%) or 2 foci (20%). At recurrence, Gleason score was 6 (67%) or {>=}7 (27%). Median interval between initial and salvage implantation was 69 months (range, 28-132 months). psPPI planning characteristics limited doses to the rectum (mean V100 = 0.5% [0.07 cc]) and urethra (V100 = 12% [0.3 cc]). At median follow-up (23.3 months; range, 8-88 months), treatment failure (n=2) resulted only in localized recurrence; both patients underwent second psPPI with follow-up PSA tests at 12 and 26 months, resulting in 0.6 and 0.7 ng/mL, respectively. American Society for Radiation Oncology PFS rates at 1, 2, and 3 years were 86.7%, 78.4%, and 62.7%, respectively, with 5 patients for whom treatment failed (n=3 with negative transrectal ultrasound

  9. Photoselective vaporization of the prostate (PVP) with green light KTP laser in the management of symptomatic benign prostatic enlargement (BPE): does the anatomy of the TURP-like cavity predict the clinical outcome?

    NASA Astrophysics Data System (ADS)

    Nseyo, Unyime

    2005-04-01

    Photoselective vaporization of the prostate (PVP) is evolving as an alternative outpatient surgical treatment to transurethral resection of the prostate (TURP) in the management of patients with symptomatic benign prostatic hypertrophy/enlargement (BPH/BPE). The purported benefits of PVP include rapid vaporization of the prostate with an instant creation of TURP-like anatomic defect, an excellent hemostasis, shorter (<24 hours) duration of catheterization, short (< 24 hours) hospital stay, and quick return to work. We retrospectively reviewed the video clips of our cases to determine whether or not the anatomic appearance of the post-PVP prostatic cavity per se could predict clinical outcome. Forty-three, non-consecutive patients, diagnosed with symptomatic BPH have been treated with PVP using the 80W KTP laser and followed for at least 18 months (range 18-24). A majority (N=32) of the patients was enrolled under an Institutional Review Board approved multi-center protocol at the Hunter McGuire Veterans Administration Medical Center, Richmond, Virginia. We reviewed the urodynamic parameters: AUA-SI, QOL, Qmax and PVR at 3, 6, 12, 18 and 24 months postoperatively. We plan to present video documentations of the various anatomic appearances of the TURP-like prostatic cavity at the conclusion of the PVP treatment along with summaries of the short and long term clinical outcomes.

  10. Parameters Favorable to Intraprostatic Radiation Dose Escalation in Men With Localized Prostate Cancer

    SciTech Connect

    Housri, Nadine; Ning, Holly; Ondos, John; Choyke, Peter; Camphausen, Kevin; Citrin, Deborah; Arora, Barbara; Shankavaram, Uma; Kaushal, Aradhana

    2011-06-01

    Purpose: To identify , within the framework of a current Phase I trial, whether factors related to intraprostatic cancer lesions (IPLs) or individual patients predict the feasibility of high-dose intraprostatic irradiation. Methods and Materials: Endorectal coil MRI scans of the prostate from 42 men were evaluated for dominant IPLs. The IPLs, prostate, and critical normal tissues were contoured. Intensity-modulated radiotherapy plans were generated with the goal of delivering 75.6 Gy in 1.8-Gy fractions to the prostate, with IPLs receiving a simultaneous integrated boost of 3.6 Gy per fraction to a total dose of 151.2 Gy, 200% of the prescribed dose and the highest dose cohort in our trial. Rectal and bladder dose constraints were consistent with those outlined in current Radiation Therapy Oncology Group protocols. Results: Dominant IPLs were identified in 24 patients (57.1%). Simultaneous integrated boosts (SIB) to 200% of the prescribed dose were achieved in 12 of the 24 patients without violating dose constraints. Both the distance between the IPL and rectum and the hip-to-hip patient width on planning CT scans were associated with the feasibility to plan an SIB (p = 0.002 and p = 0.0137, respectively). Conclusions: On the basis of this small cohort, the distance between an intraprostatic lesion and the rectum most strongly predicted the ability to plan high-dose radiation to a dominant intraprostatic lesion. High-dose SIB planning seems possible for select intraprostatic lesions.

  11. The relationship between prostate-specific antigen and prostate cancer risk: the Prostate Biopsy Collaborative Group

    PubMed Central

    Vickers, Andrew J.; Cronin, Angel M.; Roobol, Monique J.; Hugosson, Jonas; Jones, J. Stephen; Kattan, Michael W.; Klein, Eric; Hamdy, Freddie; Neal, David; Donovan, Jenny; Parekh, Dipen J.; Ankerst, Donna; Bartsch, George; Klocker, Helmut; Horninger, Wolfgang; Benchikh, Amine; Salama, Gilles; Villers, Arnauld; Freedland, Steve J.; Moreira, Daniel M.; Schröder, Fritz H.; Lilja, Hans

    2010-01-01

    PURPOSE The relationship between prostate specific antigen (PSA) level and prostate cancer risk remains subject to fundamental disagreements. We hypothesize that the risk of prostate cancer on biopsy for a given PSA level is affected by identifiable characteristics of the cohort under study. EXPERIMENTAL DESIGN We used data from 5 European and 3 US cohorts of men undergoing biopsy for prostate cancer; six were population-based studies and two were clinical cohorts. The association between PSA and prostate cancer was calculated separately for each cohort using locally-weighted scatterplot smoothing. RESULTS The final data set included 25,772 biopsies and 8,503 cancers. There were gross disparities between cohorts with respect to both the prostate cancer risk at a given PSA level and the shape of the risk curve. These disparities were associated with identifiable differences between cohorts: for a given PSA level, a greater number of biopsy cores increased risk of cancer (odds ratio for >6 vs. 6 core biopsy 1.35; 95% C.I. 1.18, 1.54; p<0.0005); recent screening led to a smaller increase in risk per unit change in PSA (p=0.001 for interaction term) and US cohorts had higher risk than the European cohorts (2.14; 95% C.I. 1.99, 2.30; p<0.0005). CONCLUSIONS Our results suggest that the relationship between PSA and risk of a positive prostate biopsy varies, both in terms of the probability of prostate cancer at a given PSA value and the shape of the risk curve. This poses challenges to the use of PSA-driven algorithms to determine whether biopsy is indicated. PMID:20736330

  12. What Is the Clinical Significance of FDG Unexpected Uptake in the Prostate in Patients Undergoing PET/CT for Other Malignancies?

    PubMed Central

    Bhosale, Priya; Balachandran, Aparna; Vikram, Raghu; Viswanathan, Chitra; Macapinlac, Homer; Rohren, Eric; Prativadi, Ramanujan

    2013-01-01

    Purpose. To determine the clinical significance of unexpected, abnormal FDG uptake in the prostate in patients undergoing FDG-PET/CT for staging of other primary malignancies without a prior history of prostate carcinoma. Methods. Retrospective search of FDG-PET/CT studies to identify patients with unexpected, abnormal FDG uptake in the prostate gland, who underwent subsequent biopsy, was performed. 26 patients were identified. Images were reviewed to determine the pattern of uptake within the prostate (focal or diffuse) and maximum standardized uptake value (SUVmax). PSA and Gleason scores were recorded. Results. 15/26 (58%) patients were found to have prostate carcinoma. Gleason scores ranged from 6 to 9.9. There was no statistical difference in the pattern of uptake (focal versus diffuse) or the SUVmax. Serum PSA levels with cancer (range, 2–26.8 ng; mean, 10.2 ng) and those without cancer (range, 2–10.5 ng; mean, 2.2 ng) were statistically significant (P < 0.007, Wilcoxon rank sum test). Conclusions. Patients with abnormal uptake in the prostate have a 58% likelihood of occult prostate cancer. In the setting of elevated serum PSA levels, abnormal prostate uptake should therefore be viewed with suspicion and a urology consult should be obtained; however, it is irrelevant in patients with underlying aggressive malignancies. PMID:24455242

  13. Assessment of photoselective vaporization of prostate skills during Urology Objective Structured Clinical Examinations (OSCE)

    PubMed Central

    Noureldin, Yasser A.; Elkoushy, Mohamed A.; Fahmy, Nader; Carrier, Serge; Elhilali, Mostafa M.; Andonian, Sero

    2015-01-01

    Introduction: We evaluated the use of the GreenLight Simulator (GL-SIM) (American Medical Systems, Guelph, ON) in the skill assessment of postgraduate trainees (PGTs) in photoselective vaporization of the prostate (PVP). We also sought to determine whether previous PVP experience or GL-SIM practice improved performance. Methods: PGTs in postgraduate years (PGY-3 to PGY-5) from all 4 Quebec urology training programs were recruited during 2 annual Objective Structured Clinical Examinations (OSCEs). During a 20-minute OSCE station, PGTs were asked to perform 2 exercises: (1) identification of endoscopic landmarks and (2) a PVP of a 30-g normal prostate. Grams vaporized, global scores, and number of correct anatomical landmarks were recorded and correlated with PGY level, practice on the GL-SIM, and previous PVP experience. Results: In total, 25 PGTs were recruited at each OSCE, with 13 PGTs participating in both OSCEs. When comparing scores from the first and second OSCEs, there was a significant improvement in the number of grams vaporized (2.9 vs. 4.3 g; p = 0.003) and global score (100 vs. 165; p = 0.03). There was good correlation between the number of previously performed PVPs and the global score (r = 0.4, p = 0.04). Similarly, PGTs with previous practice on the GL-SIM had significantly higher global score (100.6 vs. 162.6; p = 0.04) and grams vaporized (3.1 vs. 4.1 g; p = 0.04) when compared with those who did not practice on GL-SIM. Furthermore, there were significantly more competent PGTs among those who had previously practiced on the GL-SIM (32.7% vs. 10.2%; p = 0.009). PGY level did not significantly affect grams vaporized or global score (p > 0.05). Conclusion: Performance on the GL-SIM at OSCEs significantly correlated with previous practice on the GL-SIM and previous PVP experience rather than PGY level. Furthermore, there were significantly more competent PGTs among those who had previously practiced on the GL-SIM. PMID:25737763

  14. Proton beam therapy: clinical utility and current status in prostate cancer

    PubMed Central

    Yamoah, Kosj; Johnstone, Peter AS

    2016-01-01

    Proton beam therapy has recently become available to a broader population base. There remains much controversy about its routine use in prostate cancer. We provide an analysis of the existing literature regarding efficacy and toxicity of the technique. Currently, the use of proton beam therapy for prostate cancer is largely dependent on continued reimbursement for the practice. While there are potential benefits supporting the use of protons in prostate cancer, the low risk of toxicity using existing techniques and the high cost of protons contribute to lower the value of the technique. PMID:27695349

  15. Proton beam therapy: clinical utility and current status in prostate cancer

    PubMed Central

    Yamoah, Kosj; Johnstone, Peter AS

    2016-01-01

    Proton beam therapy has recently become available to a broader population base. There remains much controversy about its routine use in prostate cancer. We provide an analysis of the existing literature regarding efficacy and toxicity of the technique. Currently, the use of proton beam therapy for prostate cancer is largely dependent on continued reimbursement for the practice. While there are potential benefits supporting the use of protons in prostate cancer, the low risk of toxicity using existing techniques and the high cost of protons contribute to lower the value of the technique.

  16. Split-Course, High-Dose Palliative Pelvic Radiotherapy for Locally Progressive Hormone-Refractory Prostate Cancer

    SciTech Connect

    Gogna, Nirdosh Kumar; Baxi, Siddhartha; Hickey, Brigid; Baumann, Kathryn; Burmeister, Elizabeth; Holt, Tanya

    2012-06-01

    Purpose: Local progression, in patients with hormone-refractory prostate cancer, often causes significant morbidity. Pelvic radiotherapy (RT) provides effective palliation in this setting, with most published studies supporting the use of high-dose regimens. The aim of the present study was to examine the role of split-course hypofractionated RT used at our institution in treating this group of patients. Methods and Materials: A total of 34 men with locoregionally progressive hormone-refractory prostate cancer, treated with a split course of pelvic RT (45-60 Gy in 18-24 fractions) between 2000 and 2008 were analyzed. The primary endpoints were the response rate and actuarial locoregional progression-free survival. Secondary endpoints included overall survival, compliance, and acute and late toxicity. Results: The median age was 71 years (range, 53-88). Treatment resulted in an overall initial response rate of 91%, a median locoregional progression-free survival of 43 months, and median overall survival of 28 months. Compliance was excellent and no significant late toxicity was reported. Conclusions: The split course pelvic RT described has an acceptable toxicity profile, is effective, and compares well with other high-dose palliative regimens that have been previously reported.

  17. To Share or Not to Share: Malaysian Healthcare Professionals' Views on Localized Prostate Cancer Treatment Decision Making Roles

    PubMed Central

    Lee, Yew Kong; Lee, Ping Yein; Cheong, Ai Theng; Ng, Chirk Jenn; Abdullah, Khatijah Lim; Ong, Teng Aik; Razack, Azad Hassan Abdul

    2015-01-01

    Aim To explore the views of Malaysian healthcare professionals (HCPs) on stakeholders’ decision making roles in localized prostate cancer (PCa) treatment. Methods Qualitative interviews and focus groups were conducted with HCPs treating PCa. Data was analysed using a thematic approach. Four in-depth interviews and three focus group discussions were conducted between December 2012 and March 2013 using a topic guide. Interviews were audio-recorded, transcribed verbatim, and analysed thematically. Findings The participants comprised private urologists (n = 4), government urologists (n = 6), urology trainees (n = 6), government policy maker (n = 1) and oncologists (n = 3). HCP perceptions of the roles of the three parties involved (HCPs, patients, family) included: HCP as the main decision maker, HCP as a guide to patients’ decision making, HCP as a facilitator to family involvement, patients as main decision maker and patient prefers HCP to decide. HCPs preferred to share the decision with patients due to equipoise between prostate treatment options. Family culture was important as family members often decided on the patient’s treatment due to Malaysia’s close-knit family culture. Conclusions A range of decision making roles were reported by HCPs. It is thus important that stakeholder roles are clarified during PCa treatment decisions. HCPs need to cultivate an awareness of sociocultural norms and family dynamics when supporting non-Western patients in making decisions about PCa. PMID:26559947

  18. Gleason Pattern 5 Is the Greatest Risk Factor for Clinical Failure and Death From Prostate Cancer After Dose-Escalated Radiation Therapy and Hormonal Ablation

    SciTech Connect

    Sabolch, Aaron; Feng, Felix Y.; Daignault-Newton, Stephanie; Halverson, Schuyler; Blas, Kevin; Phelps, Laura; Olson, Karin B.; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-15

    Purpose: The division of Gleason score (GS) into three categories (2-6, 7, 8-10) may not fully use its prognostic power, as revealed by recent reports demonstrating the presence of Gleason Pattern 5 (GP5) as a strong predictor for biochemical recurrence. Therefore, we analyzed the clinical outcomes in patients treated with dose-escalated radiation therapy (RT) based on the presence or absence of GP5. Methods and Materials: Outcomes were analyzed for 718 men treated for localized prostate cancer with external-beam RT to a minimum planning target volume dose of at least 75 Gy. We assessed the impact of GP5 and that of pretreatment- and treatment-related factors on freedom from biochemical failure, freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS). Results: At biopsy, 89% of patients had no GP5, and 11% (76/718) had GP5. There were no differences in age, comorbid illness, T stage, prostate-specific antigen, or the use or duration of androgen deprivation therapy between GS8 without GP5 and GS8-10 with GP5. The presence of GP5 predicted lower FFM (p < 0.002; hazard ratio [HR] 3.4 [1.7-7.1]); CSS (p < 0.0001; HR 12.9 [5.4-31]); and OS (p < 0.0001; HR 3.6 [2.0-6.5]) in comparison with GS8 (without GP5). The 8-year FFM, CSS, and OS were 89%, 98%, and 57%, respectively, for those with Gleason 8 prostate cancer without GP5 in comparison with 61%, 55%, and 31%, respectively, for those with GP5. In addition, both FFM and CSS were strongly influenced by androgen deprivation therapy given concurrently with RT. On multivariate analysis, GP5 was the strongest prognostic factor for all clinical endpoints, including OS. Conclusion: The presence of GP5 predicts for worse clinical behavior, which therefore needs to be accounted for by risk stratification schemes. Further intensification of local and/or systemic therapy may be appropriate for such patients.

  19. MRI-guided focused ultrasound (MRgFUS) system for thermal ablation of prostate cancer: pre-clinical evaluation in canines

    NASA Astrophysics Data System (ADS)

    McDannold, Nathan; Ziso, Hadas; Assif, Benny; Hananel, Arik; Vykhodtseva, Natalia; Gretton, Peri; Pilatou, Magdalini; Haker, Steven; Tempany, Clare

    2009-02-01

    A transrectal MRgFUS system was tested in a canine prostate model. Focal volumes in each half of the prostate were targeted, with high energy in one half of the gland for ablation and in the other with lower-energy sonications to test our ability to localize the focal spot before causing thermal tissue damage. All sonications (n=155) were readily observed with proton resonance frequency (PRF) MR temperature imaging, contrast enhanced MRI and histology. The prostate gland moved during the experiments, demonstrating the need for motion tracking. The resultant focal temperature changes during the experiments were 24.2 +/- 8.2°C.

  20. Dosimetric analysis and comparison of IMRT and HDR brachytherapy in treatment of localized prostate cancer.

    PubMed

    Murali, V; Kurup, P G G; Mahadev, P; Mahalakshmi, S

    2010-04-01

    Radical radiotherapy is one of the options for the management of prostate cancer. In external beam therapy, 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) are the options for delivery of increased radiation dose, as vital organs are very close to the prostate and a higher dose to these structures leads to an increased toxicity. In brachytherapy, low dose rate brachytherapy with permanent implant of radioactive seeds and high dose rate brachytherapy (HDR) with remote after loaders are available. A dosimetric analysis has been made on IMRT and HDR brachytherapy plans. Ten cases from each IMRT and HDR brachytherapy have been taken for the study. The analysis includes comparison of conformity and homogeneity indices, D100, D95, D90, D80, D50, D10 and D5 of the target. For the organs at risk (OAR), namely rectum and bladder, V100, V90 and V50 are compared. In HDR brachytherapy, the doses to 1 cc and 0.1 cc of urethra have also been studied. Since a very high dose surrounds the source, the 300% dose volumes in the target and within the catheters are also studied in two plans, to estimate the actual volume of target receiving dose over 300%. This study shows that the prescribed dose covers 93 and 92% of the target volume in IMRT and HDR brachytherapy respectively. HDR brachytherapy delivers a much lesser dose to OAR, compared to the IMRT. For rectum, the V50 in IMRT is 34.0cc whilst it is 7.5cc in HDR brachytherapy. With the graphic optimization tool in HDR brachytherapy planning, the dose to urethra could be kept within 120% of the target dose. Hence it is concluded that HDR brachytherapy may be the choice of treatment for cancer of prostate in the early stage.

  1. Dosimetric analysis and comparison of IMRT and HDR brachytherapy in treatment of localized prostate cancer

    PubMed Central

    Murali, V.; Kurup, P. G. G.; Mahadev, P.; Mahalakshmi, S.

    2010-01-01

    Radical radiotherapy is one of the options for the management of prostate cancer. In external beam therapy, 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) are the options for delivery of increased radiation dose, as vital organs are very close to the prostate and a higher dose to these structures leads to an increased toxicity. In brachytherapy, low dose rate brachytherapy with permanent implant of radioactive seeds and high dose rate brachytherapy (HDR) with remote after loaders are available. A dosimetric analysis has been made on IMRT and HDR brachytherapy plans. Ten cases from each IMRT and HDR brachytherapy have been taken for the study. The analysis includes comparison of conformity and homogeneity indices, D100, D95, D90, D80, D50, D10 and D5 of the target. For the organs at risk (OAR), namely rectum and bladder, V100, V90 and V50 are compared. In HDR brachytherapy, the doses to 1 cc and 0.1 cc of urethra have also been studied. Since a very high dose surrounds the source, the 300% dose volumes in the target and within the catheters are also studied in two plans, to estimate the actual volume of target receiving dose over 300%. This study shows that the prescribed dose covers 93 and 92% of the target volume in IMRT and HDR brachytherapy respectively. HDR brachytherapy delivers a much lesser dose to OAR, compared to the IMRT. For rectum, the V50 in IMRT is 34.0cc whilst it is 7.5cc in HDR brachytherapy. With the graphic optimization tool in HDR brachytherapy planning, the dose to urethra could be kept within 120% of the target dose. Hence it is concluded that HDR brachytherapy may be the choice of treatment for cancer of prostate in the early stage. PMID:20589121

  2. Seminal, clinical and colour-Doppler ultrasound correlations of prostatitis-like symptoms in males of infertile couples.

    PubMed

    Lotti, F; Corona, G; Mondaini, N; Maseroli, E; Rossi, M; Filimberti, E; Noci, I; Forti, G; Maggi, M

    2014-01-01

    'Prostatitis-like symptoms' (PLS) are a cluster of bothersome conditions defined as 'perineal and/or ejaculatory pain or discomfort and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) pain subdomain score ≥4' (Nickel's criteria). PLS may originate from the prostate or from other portions of the male genital tract. Although PLS could be associated with 'prostatitis', they should not be confused. The NIH-CPSI is considered the gold-standard for assessing PLS severity. Although previous studies investigated the impact of prostatitis, vesiculitis or epididymitis on semen parameters, correlations between their related symptoms and seminal or scrotal/transrectal colour-Doppler ultrasound (CDU) characteristics have not been carefully determined. And no previous study evaluated the CDU features of PLS in infertile men. This study was aimed at investigating possible associations among NIH-CPSI (total and subdomain) scores and PLS, with seminal, clinical and scrotal/transrectal CDU parameters in a cohort of males of infertile couples. PLS of 400 men (35.8 ± 7.2 years) with a suspected male factor were assessed by the NIH-CPSI. All patients underwent, during the same day, semen analysis, seminal plasma interleukin 8 (sIL-8, a marker of male genital tract inflammation), biochemical evaluation, urine/seminal cultures, scrotal/transrectal CDU. PLS was detected in 39 (9.8%) subjects. After adjusting for age, waist and total testosterone (TT), no association among NIH-CPSI (total or subdomain) scores or PLS and sperm parameters was observed. However, we found a positive association with current positive urine and/or seminal cultures, sIL-8 levels and CDU features suggestive of inflammation of the epididymis, seminal vesicles, prostate, but not of the testis. The aforementioned significant associations of PLS were further confirmed by comparing PLS patients with age-, waist- and TT-matched PLS-free patients (1 : 3 ratio). In conclusion, NIH

  3. Health-Related Quality of Life in Patients With Locally Advanced Prostate Cancer After 76 Gy Intensity-Modulated Radiotherapy vs. 70 Gy Conformal Radiotherapy in a Prospective and Longitudinal Study

    SciTech Connect

    Lips, Irene Dehnad, Human; Kruger, Arto Boeken; Moorselaar, Jeroen van; Heide, Uulke van; Battermann, Jan; Vulpen, Marco van

    2007-11-01

    Purpose: To compare quality of life (QoL) after 70 Gy conformal radiotherapy with QoL after 76 Gy intensity-modulated radiotherapy (IMRT) in patients with locally advanced prostate carcinoma. Methods and Materials: Seventy-eight patients with locally advanced prostate cancer were treated with 70 Gy three-field conformal radiotherapy, and 92 patients received 76 Gy IMRT with fiducial markers for position verification. Quality of life was measured by RAND-36, the European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30(+3)), and the prostate-specific EORTC QLQ-PR25, before radiotherapy (baseline) and 1 month and 6 months after treatment. Quality of life changes in time (baseline vs. 1 month and baseline vs. 6 months) of {>=}10 points were considered clinically relevant. Results: Differences between the treatment groups for QoL changes over time occurred in several QoL domains. The 76-Gy group revealed no significant deterioration in QoL compared with the 70-Gy group. The IMRT 76-Gy group even demonstrated a significantly better change in QoL from baseline to 1 month in several domains. The conformal 70-Gy group revealed temporary deterioration in pain, role functioning, and urinary symptoms; for the IMRT 76-Gy group a better QoL in terms of change in health existed after 1 month, which persisted after 6 months. For both treatment groups temporary deterioration in physical role restriction occurred after 1 month, and an improvement in emotional role restriction occurred after 6 months. Sexual activity was reduced after treatment for both groups and remained decreased after 6 months. Conclusions: Intensity-modulated radiotherapy and accurate position verification seem to provide a possibility to increase the radiation dose for prostate cancer without deterioration in QoL.

  4. Clinical experience with EPID dosimetry for prostate IMRT pre-treatment dose verification

    SciTech Connect

    McDermott, L. N.; Wendling, M.; Asselen, B. van; Stroom, J.; Sonke, J.-J.; Herk, M. van; Mijnheer, B. J.

    2006-10-15

    The aim of this study was to demonstrate how dosimetry with an amorphous silicon electronic portal imaging device (a-Si EPID) replaced film and ionization chamber measurements for routine pre-treatment dosimetry in our clinic. Furthermore, we described how EPID dosimetry was used to solve a clinical problem. IMRT prostate plans were delivered to a homogeneous slab phantom. EPID transit images were acquired for each segment. A previously developed in-house back-projection algorithm was used to reconstruct the dose distribution in the phantom mid-plane (intersecting the isocenter). Segment dose images were summed to obtain an EPID mid-plane dose image for each field. Fields were compared using profiles and in two dimensions with the {gamma} evaluation (criteria: 3%/3 mm). To quantify results, the average {gamma} ({gamma}{sub avg}), maximum {gamma} ({gamma}{sub max}), and the percentage of points with {gamma}<1(P{sub {gamma}}{sub lt1}) were calculated within the 20% isodose line of each field. For 10 patient plans, all fields were measured with EPID and film at gantry set to 0 deg. . The film was located in the phantom coronal mid-plane (10 cm depth), and compared with the back-projected EPID mid-plane absolute dose. EPID and film measurements agreed well for all 50 fields, with <{gamma}{sub avg}>=0.16, <{gamma}{sub max}>=1.00, and =100%. Based on these results, film measurements were discontinued for verification of prostate IMRT plans. For 20 patient plans, the dose distribution was re-calculated with the phantom CT scan and delivered to the phantom with the original gantry angles. The planned isocenter dose (plan{sub iso}) was verified with the EPID (EPID{sub iso}) and an ionization chamber (IC{sub iso}). The average ratio, , was 1.00 (0.01 SD). Both measurements were systematically lower than planned, with and =0.99 (0.01 SD). EPID mid-plane dose images for

  5. Folic acid and risk of prostate cancer: results from a randomized clinical trial.

    PubMed

    Figueiredo, Jane C; Grau, Maria V; Haile, Robert W; Sandler, Robert S; Summers, Robert W; Bresalier, Robert S; Burke, Carol A; McKeown-Eyssen, Gail E; Baron, John A

    2009-03-18

    Data regarding the association between folate status and risk of prostate cancer are sparse and conflicting. We studied prostate cancer occurrence in the Aspirin/Folate Polyp Prevention Study, a placebo-controlled randomized trial of aspirin and folic acid supplementation for the chemoprevention of colorectal adenomas conducted between July 6, 1994, and December 31, 2006. Participants were followed for up to 10.8 (median = 7.0, interquartile range = 6.0-7.8) years and asked periodically to report all illnesses and hospitalizations. Aspirin alone had no statistically significant effect on prostate cancer incidence, but there were marked differences according to folic acid treatment. Among the 643 men who were randomly assigned to placebo or supplementation with folic acid, the estimated probability of being diagnosed with prostate cancer over a 10-year period was 9.7% (95% confidence interval [CI] = 6.5% to 14.5%) in the folic acid group and 3.3% (95% CI = 1.7% to 6.4%) in the placebo group (age-adjusted hazard ratio = 2.63, 95% CI = 1.23 to 5.65, Wald test P = .01). In contrast, baseline dietary folate intake and plasma folate in nonmultivitamin users were inversely associated with risk of prostate cancer, although these associations did not attain statistical significance in adjusted analyses. These findings highlight the potential complex role of folate in prostate cancer and the possibly different effects of folic acid-containing supplements vs natural sources of folate.

  6. Impact of Cosmetic Result on Selection of Surgical Treatment in Patients With Localized Prostate Cancer

    PubMed Central

    Martinez-Salamanca, Juan Ignacio; Maestro, Mario Alvarez; Galarza, Ignacio Sola; Rodriguez, Joaquin Carballido

    2014-01-01

    Objectives: To analyze the effect of cosmetic outcome as an isolated variable in patients undergoing surgical treatment based on the incision used in the 3 variants of radical prostatectomy: open (infraumbilical incision and Pfannestiel incision) and laparoscopic, or robotic (6 ports) surgery. Patients and methods: 612 male patients 40 to 70 years of age with a negative history of prostate disease were invited to participate. Each patient was evaluated by questionnaire accompanied by a set of 6 photographs showing the cosmetic appearance of the 3 approaches, with and without undergarments. Participants ranked the approaches according to preference, on the basis of cosmesis. We also recorded demographic variables: age, body mass index, marital status, education level, and physical activity. Results: Of the 577 patients who completed the questionnaries, the 6-port minimally invasive approach represents the option preferred by 52% of the participants, followed by the Pfannestiel incision (46%), and the infraumbilical incision (11%), respectively. The univariate and multivariate analyses did not show statistically significant differences when comparing the approach preferred by the patients and the sub-analyses for demographic variables, except for patients who exercised who preferred the Pfannestiel incision (58%) instead of minimally invasive approach (42%) with statistically significant differences. Conclusion: The minimally invasive approach was the approach of choice for the majority of patients in the treatment of prostate cancer. The Pfannestiel incision represents an acceptable alternative. More research and investment may be necesary to improve cosmetic outcomes. PMID:25516703

  7. Intermittent androgen ablation in patients with biochemical failure after pelvic radiotherapy for localized prostate cancer

    SciTech Connect

    Cury, Fabio L.B.; Souhami, Luis . E-mail: luis.souhami@muhc.mcgill.ca; Rajan, Raghu; Tanguay, Simon; Gagnon, Bruno; Duclos, Marie; Shenouda, George; Faria, Sergio L.; David, Marc; Freeman, Carolyn R.

    2006-03-01

    Purpose: To assess the efficacy of intermittent androgen ablation (IAA) in patients with biochemical failure after radiotherapy for prostate cancer. Methods and Materials: Thirty-nine patients received a luteinizing hormone-releasing hormone analog every 2 months for a total of 4 doses. IAA was then discontinued if serum prostate-specific antigen (PSA) fell to a normal level with a castrate level of testosterone. Therapy was restarted when the serum PSA level reached {>=}10 ng/mL and was discontinued if hormone resistance or unacceptable toxicity occurred. Results: Median PSA was 9.1 ng/mL at the time of first IAA. The median time between the first and the second cycles was 20.1 months, decreasing to 15.5 months between the third and fourth cycles. Two patients discontinued the treatment because of severe hot flushes. Four patients developed hormone resistance. With a median follow-up of 56.4 months, 5-year survival is 92.3%. Three patients died of unrelated causes. The incidence of distant metastasis is 6.8%. Conclusions: The use of IAA seems to be a safe and effective treatment for patients with biochemical failure post radiotherapy and no evidence of metastatic disease. The use of IAA limits hormone-related side effects and health care costs without an apparent increase in the risk for the development of metastatic disease.

  8. HDAC6 Regulates Androgen Receptor Hypersensitivity and Nuclear Localization via Modulating Hsp90 Acetylation in Castration-Resistant Prostate Cancer

    PubMed Central

    Ai, Junkui; Wang, Yujuan; Dar, Javid A.; Liu, June; Liu, Lingqi; Nelson, Joel B.; Wang, Zhou

    2009-01-01

    The development of castration-resistant prostate cancer (PCa) requires that under castration conditions, the androgen receptor (AR) remains active and thus nuclear. Heat shock protein 90 (Hsp90) plays a key role in androgen-induced and -independent nuclear localization and activation of AR. Histone deacetylase 6 (HDAC6) is implicated, but has not been proven, in regulating AR activity via modulating Hsp90 acetylation. Here, we report that knockdown of HDAC6 in C4-2 cells using short hairpin RNA impaired ligand-independent nuclear localization of endogenous AR and inhibited PSA expression and cell growth in the absence or presence of dihydrotestosterone (DHT). The dose-response curve of DHT-stimulated C4-2 colony formation was shifted by shHDAC6 such that approximately 10-fold higher concentration of DHT is required, indicating a requirement for HDAC6 in AR hypersensitivity. HDAC6 knockdown also inhibited C4-2 xenograft tumor establishment in castrated, but not in testes-intact, nude mice. Studies using HDAC6-deficient mouse embryonic fibroblasts cells showed that inhibition of AR nuclear localization by HDAC6 knockdown can be largely alleviated by expressing a deacetylation mimic Hsp90 mutant. Taken together, our studies suggest that HDAC6 regulates AR hypersensitivity and nuclear localization, mainly via modulating HSP90 acetylation. Targeting HDAC6 alone or in combination with other therapeutic approaches is a promising new strategy for prevention and/or treatment of castration-resistant PCa. PMID:19855091

  9. HDAC6 regulates androgen receptor hypersensitivity and nuclear localization via modulating Hsp90 acetylation in castration-resistant prostate cancer.

    PubMed

    Ai, Junkui; Wang, Yujuan; Dar, Javid A; Liu, June; Liu, Lingqi; Nelson, Joel B; Wang, Zhou

    2009-12-01

    The development of castration-resistant prostate cancer (PCa) requires that under castration conditions, the androgen receptor (AR) remains active and thus nuclear. Heat shock protein 90 (Hsp90) plays a key role in androgen-induced and -independent nuclear localization and activation of AR. Histone deacetylase 6 (HDAC6) is implicated, but has not been proven, in regulating AR activity via modulating Hsp90 acetylation. Here, we report that knockdown of HDAC6 in C4-2 cells using short hairpin RNA impaired ligand-independent nuclear localization of endogenous AR and inhibited PSA expression and cell growth in the absence or presence of dihydrotestosterone (DHT). The dose-response curve of DHT-stimulated C4-2 colony formation was shifted by shHDAC6 such that approximately 10-fold higher concentration of DHT is required, indicating a requirement for HDAC6 in AR hypersensitivity. HDAC6 knockdown also inhibited C4-2 xenograft tumor establishment in castrated, but not in testes-intact, nude mice. Studies using HDAC6-deficient mouse embryonic fibroblasts cells showed that inhibition of AR nuclear localization by HDAC6 knockdown can be largely alleviated by expressing a deacetylation mimic Hsp90 mutant. Taken together, our studies suggest that HDAC6 regulates AR hypersensitivity and nuclear localization, mainly via modulating HSP90 acetylation. Targeting HDAC6 alone or in combination with other therapeutic approaches is a promising new strategy for prevention and/or treatment of castration-resistant PCa.

  10. Clinical map document based on XML (cMDX): document architecture with mapping feature for reporting and analysing prostate cancer in radical prostatectomy specimens

    PubMed Central

    2010-01-01

    Background The pathology report of radical prostatectomy specimens plays an important role in clinical decisions and the prognostic evaluation in Prostate Cancer (PCa). The anatomical schema is a helpful tool to document PCa extension for clinical and research purposes. To achieve electronic documentation and analysis, an appropriate documentation model for anatomical schemas is needed. For this purpose we developed cMDX. Methods The document architecture of cMDX was designed according to Open Packaging Conventions by separating the whole data into template data and patient data. Analogue custom XML elements were considered to harmonize the graphical representation (e.g. tumour extension) with the textual data (e.g. histological patterns). The graphical documentation was based on the four-layer visualization model that forms the interaction between different custom XML elements. Sensible personal data were encrypted with a 256-bit cryptographic algorithm to avoid misuse. In order to assess the clinical value, we retrospectively analysed the tumour extension in 255 patients after radical prostatectomy. Results The pathology report with cMDX can represent pathological findings of the prostate in schematic styles. Such reports can be integrated into the hospital information system. "cMDX" documents can be converted into different data formats like text, graphics and PDF. Supplementary tools like cMDX Editor and an analyser tool were implemented. The graphical analysis of 255 prostatectomy specimens showed that PCa were mostly localized in the peripheral zone (Mean: 73% ± 25). 54% of PCa showed a multifocal growth pattern. Conclusions cMDX can be used for routine histopathological reporting of radical prostatectomy specimens and provide data for scientific analysis. PMID:21078179

  11. Prostate Planning Treatment Volume Margin Calculation Based on the ExacTrac X-Ray 6D Image-Guided System: Margins for Various Clinical Implementations

    SciTech Connect

    Alonso-Arrizabalaga, Sara Brualla Gonzalez, Luis; Rosello Ferrando, Juan V.; Pastor Peidro, Jorge; Lopez Torrecilla, Jose; Planes Meseguer, Domingo; Garcia Hernandez, Trinidad

    2007-11-01

    Purpose: To assess the prostate motion from day-to-day setup, as well as during irradiation time, to calculate planning target volume (PTV) margins. PTV margins differ depending on the clinical implementation of an image-guided system. Three cases were considered in this study: daily bony anatomy match, center of gravity of the implanted marker seeds calculated with a limited number of imaged days, and daily online correction based on implanted marker seeds. Methods and Materials: A cohort of 30 nonrandomized patients and 1,330 pairs of stereoscopic kV images have been used to determine the prostate movement. The commercial image guided positioning tool employed was ExacTrac X-Ray 6D (BrainLAB AG, Feldkirchen, Germany). Results: Planning target volume margins such that a minimum of 95% of the prescribed dose covers the clinical target volume for 90% of the population are presented. PTV margins based on daily bony anatomy match, including intrafraction correction, would be 11.5, 13.5, and 4.5 mm in the anterior-posterior, superior-inferior, and right-left directions, respectively. This margin can be further reduced to 8.1, 8.6, and 4.8 mm (including intrafraction motion) if implanted marker seeds are used. Finally, daily on line correction based on marker seeds would result in the smallest of the studied margins: 4.7, 6.2, and 1.9 mm. Conclusion: Planning target volume margins are dependent on the local clinical use of the image-guided RT system available in any radiotherapy department.

  12. Chronic prostatitis: Current concepts

    PubMed Central

    Vaidyanathan, Ram; Mishra, Vibhash C.

    2008-01-01

    Purpose: Chronic prostatitis (CP) is a common condition. It causes significant suffering to the patients and constitutes a sizeable workload for the urologists. The purpose of this review is to describe the currently accepted concepts regarding the aspects of CP. Materials and Methods: Relevant papers on the epidemiology, etiology, diagnosis, evaluation and management of CP were identified through a search of MEDLINE using text terms “prostatitis”, “chronic prostatitis” and “chronic pelvic pain syndrome”. The list of articles thus obtained was supplemented by manual search of bibliographies of the identified articles and also by exploring the MEDLINE option “Related Articles”. Results: The salient points of the relevant articles on each aspect of CP have been summarized in the form of a non-systematic narrative review. Conclusion: Chronic prostatitis is caused by a variety of infective and non-infective factors and is characterized by a rather long remitting and relapsing clinical course. The diagnosis is based on symptoms comprising pain and nonspecific urinary and/or ejaculatory disturbances and microbiological tests to localize bacteria and/or leucocytes in segmented urinary tract specimens. The contemporary classification was proposed by the National Institutes of Health/National Institute of Diabetes Digestive Kidney Diseases (NIH/NIDDK). National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) is the patient evaluation tool used extensively in clinical practice and research. Management should be individualized, multimodal and of an appropriate duration. PMID:19468353

  13. Preliminary Clinical Experience of trans-1-Amino-3-(18)F-fluorocyclobutanecarboxylic Acid (anti-(18)F-FACBC) PET/CT Imaging in Prostate Cancer Patients

    PubMed Central

    Partanen, Kaarina; Joensuu, Timo

    2014-01-01

    Background. In this retrospective analysis we assessed the role of [18F]-FACBC-PET/CT in the prostatic cancer staging. Procedure. 30 first [18F]-FACBC-PET/CT images of 26 patients (68.1 ± 5.8 years) were analyzed. PET/CT findings were compared with PSA concentrations, with PSA doubling times (PDT), and with correlative imaging. Results. On 16 [18F]-FACBC (53.3%) scans, 58 metabolically active lesions were found. 12 (20.7%) lesions corresponding to the local relapse were found in prostate/prostate bed and seminal vesicles, 9 (15.5%) lesions were located in regional lymph nodes, 10 (17.2%) were located in distal lymph nodes, and 26 (44.8%) metabolically active lesions were found in the skeleton. In one case, focal uptake was found in the brain, confirmed further on MRI as meningioma. The mean S-PSA level in patients with positive [18F]-FACBC findings was 9.5 ± 16.9 μg/L (0.54–69 μg/L) and in patients with negative [18F]-FACBC findings was 1.96 ± 1.87 μg/L (0.11–5.9 μg/L), but the difference was not statistically significant. However, the PSA doubling time (PDT) in patients with positive findings was significantly shorter than PDT in patients with negative findings: 3.25 ± 2.09 months (0.3–6 months) versus 31.2 ± 22.02 months (8–84 months), P < 0.0001. There was a strong positive correlation between PSA value and number of metabolically active lesions (R = 0.74) and a negative correlation between PDT and number of metabolically active lesions (R = −0.56). There was a weak negative correlation between PDT and SUVmax⁡ (R = −0.30). Conclusion. According to our preliminary clinical experience, [18F]-FACBC-PET may play a role in in vivo restaging of an active prostate cancer, especially in patients with a short S-PSA doubling time. PMID:24991547

  14. VHF-induced thermoacoustic imaging of fresh human prostates using a clinical ultrasound transducer array

    NASA Astrophysics Data System (ADS)

    Patch, S. K.; See, W. A.

    2016-03-01

    The purpose of this work was to demonstrate that a clinical ultrasound transducer array can practically detect thermoacoustic pulses induced by irradiation by very high frequency (VHF) electromagnetic energy. This is an important step because thermoacoustic signal strength is directly proportional to the specific absorption rate (SAR), which is lower in the VHF regime than in microwave or optical regimes. A 96-channel transducer array (P4-1) providing 3 cm coverage was incorporated into a benchtop thermoacoustic imaging system for imaging fresh surgical specimens. Thermoacoustic signal was generated by 700 ns irradiation pulses with 11 kV/m electric field strength and 108 MHz carrier frequency. To improve SNR 1024 pulses were averaged at a 250 Hz repetition rate. Two sets of sinograms were acquired, separated by a 2 cm translation along the tomographic axis and reconstructed over a 6 x 6 x 5 cm3 volume. Contrast and in-plane resolution were measured by imaging a homogeneous cylindrical phantom and an 80- micron wire designed to highlight E-field polarization effects. FWHM of the in-plane point spread function varied from 250 microns to 1.1 mm, depending upon transducer used and phantom orientation relative to the electric field. Several fresh human prostates were imaged immediately after surgery. Rudimentary comparison to histology was performed and volumetric reconstruction of the multi-channel P4-1 data visualizes anatomic features that are rarely seen in ultrasound, CT, or MRI. The single element transducer provided superior image contrast, but with inferior resolution.

  15. Advanced prostate cancer: Every Voice Matters.

    PubMed

    Payne, Heather; Westcott, Gemma

    2015-01-01

    Heather Payne speaks to Gemma Westcott, Commissioning Editor: Heather Payne was appointed as a consultant in Clinical Oncology at University College Hospital (London, UK) in 1997. Following her training at St Mary's Hospital London Medical School and after qualifying, she spent time working in general medicine in both London and Haiti. Currently, she specializes in the management of urological malignancies, and is actively involved in clinical research as well as being the principal investigator in a number of international multicenter and local studies. She enjoys helping patients with quality of life and decision-making issues with regard to their treatment options. In addition, she is the chairman of the British Uro-oncology Group, and is a member of the Department of Health Prostate Cancer Advisory Group. Further to this, she is a trustee of the Prostate Cancer Research Centre and clinical lead for the National Prostate Cancer Audit. PMID:26075438

  16. Clinical Toxicities and Dosimetric Parameters After Whole-Pelvis Versus Prostate-Only Intensity-Modulated Radiation Therapy for Prostate Cancer

    SciTech Connect

    Deville, Curtiland; Both, Stefan; Hwang, Wei-Ting; Tochner, Zelig; Vapiwala, Neha

    2010-11-01

    Purpose: To assess whether whole-pelvis (WP) intensity-modulated radiation therapy (IMRT) is associated with increased toxicity compared with prostate-only (PO) IMRT. Methods and Materials: We retrospectively analyzed all patients with prostate cancer undergoing definitive IMRT to 79.2 Gy with concurrent androgen deprivation at our institution from November 2005 to May 2007 with a minimum follow-up of 12 months. Thirty patients received initial WP IMRT to 45 Gy in 1.8-Gy fractions, and thirty patients received PO IMRT. Study patients underwent computed tomography simulation and treatment planning by use of predefined dose constraints. Bladder and rectal dose-volume histograms, maximum genitourinary (GU) and gastrointestinal (GI) Radiation Therapy Oncology Group toxicity grade, and late Grade 2 or greater toxicity-free survival curves were compared between the two groups by use of the Student t test, Fisher exact test, and Kaplan-Meier curve, respectively. Results: Bladder minimum dose, mean dose, median dose, volume receiving 5 Gy, volume receiving 20 Gy, volume receiving 40 Gy, and volume receiving 45 Gy and rectal minimum dose, median dose, and volume receiving 20 Gy were significantly increased in the WP group (all p values < 0.01). Maximum acute GI toxicity was limited to Grade 2 and was significantly increased in the WP group at 50% vs. 13% the PO group (p = 0.006). With a median follow-up of 24 months (range, 12-35 months), there was no difference in late GI toxicity (p = 0.884) or in acute or late GU toxicity. Conclusions: Despite dosimetric differences in the volume of bowel, bladder, and rectum irradiated in the low-dose and median-dose regions, WP IMRT results only in a clinically significant increase in acute GI toxicity, in comparison to PO IMRT, with no difference in GU or late GI toxicity.

  17. A patient-level data meta-analysis of standard-of-care treatments from eight prostate cancer clinical trials

    PubMed Central

    Geifman, N.; Butte, A.J

    2016-01-01

    Open clinical trial data offer many opportunities for the scientific community to independently verify published results, evaluate new hypotheses and conduct meta-analyses. These data provide valuable opportunities for scientific advances in medical research. Herein we present the comparative meta-analysis of different standard of care treatments from newly available comparator arm data from several prostate cancer clinical trials. Comparison of survival rates following treatment with mitoxantrone or docetaxel in combination with prednisone as well as prednisone alone, validated the previously demonstrated superiority of treatment with docetaxel. Additionally, comparison of four testosterone suppression treatments in hormone-refractory prostate cancer revealed that subjects who had undergone surgical castration had significantly lower survival rates than those treated with LHRH, anti-androgen or LHRH plus anti-androgen, suggesting that this treatment option is less optimal. This study illustrates how the use of patient-level clinical trial data enables meta-analyses that can provide new insights into clinical outcomes of standard of care treatments and thus, once validated, has the potential to help optimize healthcare delivery. PMID:27163794

  18. The Role of Proteomics in Biomarker Development for Improved Patient Diagnosis and Clinical Decision Making in Prostate Cancer.

    PubMed

    Tonry, Claire L; Leacy, Emma; Raso, Cinzia; Finn, Stephen P; Armstrong, John; Pennington, Stephen R

    2016-01-01

    Prostate Cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Although increased expression of prostate-specific antigen (PSA) is an effective indicator for the recurrence of PCa, its intended use as a screening marker for PCa is of considerable controversy. Recent research efforts in the field of PCa biomarkers have focused on the identification of tissue and fluid-based biomarkers that would be better able to stratify those individuals diagnosed with PCa who (i) might best receive no treatment (active surveillance of the disease); (ii) would benefit from existing treatments; or (iii) those who are likely to succumb to disease recurrence and/or have aggressive disease. The growing demand for better prostate cancer biomarkers has coincided with the development of improved discovery and evaluation technologies for multiplexed measurement of proteins in bio-fluids and tissues. This review aims to (i) provide an overview of these technologies as well as describe some of the candidate PCa protein biomarkers that have been discovered using them; (ii) address some of the general limitations in the clinical evaluation and validation of protein biomarkers; and (iii) make recommendations for strategies that could be adopted to improve the successful development of protein biomarkers to deliver improvements in personalized PCa patient decision making. PMID:27438858

  19. The Role of Proteomics in Biomarker Development for Improved Patient Diagnosis and Clinical Decision Making in Prostate Cancer

    PubMed Central

    Tonry, Claire L.; Leacy, Emma; Raso, Cinzia; Finn, Stephen P.; Armstrong, John; Pennington, Stephen R.

    2016-01-01

    Prostate Cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Although increased expression of prostate-specific antigen (PSA) is an effective indicator for the recurrence of PCa, its intended use as a screening marker for PCa is of considerable controversy. Recent research efforts in the field of PCa biomarkers have focused on the identification of tissue and fluid-based biomarkers that would be better able to stratify those individuals diagnosed with PCa who (i) might best receive no treatment (active surveillance of the disease); (ii) would benefit from existing treatments; or (iii) those who are likely to succumb to disease recurrence and/or have aggressive disease. The growing demand for better prostate cancer biomarkers has coincided with the development of improved discovery and evaluation technologies for multiplexed measurement of proteins in bio-fluids and tissues. This review aims to (i) provide an overview of these technologies as well as describe some of the candidate PCa protein biomarkers that have been discovered using them; (ii) address some of the general limitations in the clinical evaluation and validation of protein biomarkers; and (iii) make recommendations for strategies that could be adopted to improve the successful development of protein biomarkers to deliver improvements in personalized PCa patient decision making. PMID:27438858

  20. Open radical retropubic prostatectomy 2007: the true minimally invasive surgery for localized prostate cancer?

    PubMed

    Nosnik, Israel P; Gan, Tong J; Moul, Judd W

    2007-09-01

    The introduction of robotic laparoscopic assisted prostatectomy at our institution and nationwide has been a great advancement and has caused us to focus and fine-tune our goal for improvements in prostate cancer outcomes whether the patient elects for robotic laparoscopic assisted prostatectomy or open minimally invasive radical retropubic prostatectomy. While these authors favor the open technique performed by highly skilled urologic surgical oncologists, the lessons we have learned to date suggest that it is the skill of the surgeon that determines outcome, regardless of whether or not the operation is performed by an open or robotic laparoscopic technique. The concepts we have articulated here are related to resection and avoidance of positive margins, limited intraoperative blood loss and pain control, which allow equivalence in these outcome areas, regardless of technique.

  1. Leptin signalling, obesity and prostate cancer: molecular and clinical perspective on the old dilemma.

    PubMed

    Alshaker, Heba; Sacco, Keith; Alfraidi, Albandri; Muhammad, Aun; Winkler, Mathias; Pchejetski, Dmitri

    2015-11-01

    The prevalence of global obesity is increasing. Obesity is associated with general cancer-related morbidity and mortality and is a known risk factor for development of specific cancers. A recent large systematic review of 24 studies based on meta-analysis of 11,149 patients with prostate cancer showed a significant correlation between obesity and the risk of advanced prostate cancer. Further, a sustained reduction in BMI correlates with a decreased risk of developing aggressive disease. On the other hand, the correlation between consuming different products and prostate cancer occurrence/risk is limited.Here, we review the role of adipose tissue from an endocrine perspective and outline the effect of adipokines on cancer metabolism, with particular focus on leptin. Leptin exerts its physiological and pathological effects through modification of intracellular signalling, most notably activating the Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway and recently shown sphingolipid pathway. Both high levels of leptin in circulation and leptin receptor mutation are associated with prostate cancer risk in human patients; however, the in vivo mechanistic evidence is less conclusive.Given the complexity of metabolic cancer pathways, it is possible that leptin may have varying effects on prostate cancer at different stages of its development, a point that may be addressed by further epidemiological studies.

  2. Androgen receptor targeted therapies in castration-resistant prostate cancer: Bench to clinic.

    PubMed

    Imamura, Yusuke; Sadar, Marianne D

    2016-08-01

    The androgen receptor is a transcription factor and validated therapeutic target for prostate cancer. Androgen deprivation therapy remains the gold standard treatment, but it is not curative, and eventually the disease will return as lethal castration-resistant prostate cancer. There have been improvements in the therapeutic landscape with new agents approved, such as abiraterone acetate, enzalutamide, sipuleucel-T, cabazitaxel and Ra-223, in the past 5 years. New insight into the mechanisms of resistance to treatments in advanced disease is being and has been elucidated. All current androgen receptor-targeting therapies inhibit the growth of prostate cancer by blocking the ligand-binding domain, where androgen binds to activate the receptor. Persuasive evidence supports the concept that constitutively active androgen receptor splice variants lacking the ligand-binding domain are one of the resistant mechanisms underlying advanced disease. Transcriptional activity of the androgen receptor requires a functional AF-1 region in its N-terminal