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Sample records for clinically localized prostate

  1. Management of Clinically Localized Prostate Cancer

    PubMed Central

    Lepor, Herbert

    2004-01-01

    Critics of screening have stated that early detection of prostate cancer does not necessarily reflect a diminishing death rate from the disease. However, several recent reports have demonstrated that the death rate from prostate cancer is decreasing, representing the most compelling validation for aggressive screening. Prostate cancer can be halted only if there is no evidence of systemic or regional metastases and the disease is confined to the surgical field or the radiation template. Surgeons and radiation oncologists must make a concerted effort to exclude men with regional and systemic metastases who are unlikely to benefit from treatment. With the widespread acceptance of prostate-specific antigen screening, a greater proportion of men are being diagnosed with clinically localized prostate cancer. Both radical prostatectomy and radiation therapy are able to halt disease spread in this significant subset of men, but survival outcomes indicate that radical prostatectomy is a more reliable treatment than radiation therapy for clinically localized prostate cancer. Overall, the immediate treatment-related morbidity of radical prostatectomy and radiation therapy in the modern era is quite low. Radical prostatectomy and radiation therapy appear to have a similar impact on continence and erectile function. There is a need for neoadjuvant and adjuvant therapies that can be utilized in those cases where radical prostatectomy and radiation are less likely to completely eradicate or destroy the cancer. PMID:16985859

  2. 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 ...

  3. Brachytherapy for clinically localized prostate cancer: optimal patient selection.

    PubMed

    Kollmeier, Marisa A; Zelefsky, Michael J

    2011-10-01

    The objective of this review is to present an overview of each modality and delineate how to best select patients who are optimal candidates for these treatment approaches. Prostate brachytherapy as a curative modality for clinically localized prostate cancer has become increasingly utilized over the past decade; 25% of all early cancers are now treated this way in the United States (1). The popularity of this treatment strategy lies in the highly conformal nature of radiation dose, low morbidity, patient convenience, and high efficacy rates. Prostate brachytherapy can be delivered by either a permanent interstitial radioactive seed implantation (low dose rate [LDR]) or a temporary interstitial insertion of iridium-192 (Ir192) afterloading catheters. The objective of both of these techniques is to deliver a high dose of radiation to the prostate gland while exposing normal surrounding tissues to minimal radiation dose. Brachytherapy techniques are ideal to achieve this goal given the close proximity of the radiation source to tumor and sharp fall off of the radiation dose cloud proximate to the source. Brachytherapy provides a powerful means of delivering dose escalation above and beyond that achievable with intensity-modulated external beam radiotherapy alone. Careful selection of appropriate patients for these therapies, however, is critical for optimizing both disease-related outcomes and treatment-related toxicity.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. [Prostate localization systems for prostate radiotherapy].

    PubMed

    de Crevoisier, R; Lagrange, J-L; Messai, T; M'Barek, B; Lefkopoulos, D

    2006-11-01

    The development of sophisticated conformal radiation therapy techniques for prostate cancer, such as intensity-modulated radiotherapy, implies precise and accurate targeting. Inter- and intrafraction prostate motion can be significant and should be characterized, unless the target volume may occasionally be missed. Indeed, bony landmark-based portal imaging does not provide the positional information for soft-tissue targets (prostate and seminal vesicles) or critical organs (rectum and bladder). In this article, we describe various prostate localization systems used before or during the fraction: rectal balloon, intraprostatic fiducials, ultrasound-based localization, integrated CT/linear accelerator system, megavoltage or kilovoltage cone-beam CT, Calypso 4D localization system tomotherapy, Cyberknife and Exactrac X-Ray 6D. The clinical benefit in using such prostate localization tools is not proven by randomized studies and the feasibility has just been established for some of these techniques. Nevertheless, these systems should improve local control by a more accurate delivery of an increased prescribed dose in a reduced planning target volume.

  9. 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

  10. Loss of PTEN expression is associated with increased risk of recurrence after prostatectomy for clinically localized prostate cancer.

    PubMed

    Chaux, Alcides; Peskoe, Sarah B; Gonzalez-Roibon, Nilda; Schultz, Luciana; Albadine, Roula; Hicks, Jessica; De Marzo, Angelo M; Platz, Elizabeth A; Netto, George J

    2012-11-01

    PTEN (phosphatase and tensin homolog on chromosome 10) is one of the most frequently lost tumor suppressor genes in human cancers and it has been described in more than two-thirds of patients with advanced/aggressive prostate cancer. Previous studies suggest that, in prostate cancer, genomic PTEN loss is associated with tumor progression and poor prognosis. Thus, we evaluated whether immunohistochemical PTEN expression in prostate cancer glands was associated with higher risk of recurrence, using a nested case-control study that included 451 men who recurred and 451 men who did not recur with clinically localized prostate cancer treated by radical prostatectomy. Recurrence was defined as biochemical recurrence (serum prostate-specific antigen >0.2 ng/ml) or clinical recurrence (local recurrence, systemic metastases, or prostate cancer-related death). Cases and controls were matched on pathological T stage, Gleason score, race/ethnicity, and age at surgery. Odds ratios of recurrence and 95% confidence intervals were estimated using conditional logistic regression to account for the matching factors and to adjust for year of surgery, preoperative prostate-specific antigen concentrations, and status of surgical margins. Men who recurred had a higher proportion of PTEN negative expression (16 vs 11%, P=0.05) and PTEN loss (40 vs 31%, P=0.02) than controls. Men with markedly decreased PTEN staining had a higher risk of recurrence (odds ratio=1.67; 95% confidence intervals 1.09, 2.57; P=0.02) when compared with all other men. In summary, in patients with clinically localized prostate cancer treated by prostatectomy, decreased PTEN expression was associated with an increased risk of recurrence, independent of known clinicopathological factors.

  11. 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

  12. Long-term Continence Outcomes in Men Undergoing Radical Prostatectomy for Clinically Localized Prostate Cancer

    PubMed Central

    Prabhu, Vinay; Sivarajan, Ganesh; Glen, B; Taksler, Juliana Laze; Lepor, Herbert

    2014-01-01

    Background Urinary incontinence is a common short-term complication of radical prostatectomy (RP). Little is known about the long-term impact of RP on continence. Objective To elucidate the long-term progression of continence after RP. Design, setting, and participants From October 2000 through September 2012, 1788 men undergoing open RP for clinically localized prostate cancer by a single surgeon at an urban tertiary care center prospectively signed consent to be followed before RP and at 3, 6, 12, 24, 96, and 120 mo after RP. A consecutive sampling method was used and all men were included in this study. Intervention Men underwent open RP Outcome measurements and statistical analysis Regression models controlled for preoperative University of California, Los Angeles–Prostate Cancer Index urinary function score (UCLA-PCI-UFS), age, prostate-specific antigen level, Gleason score, stage, nerve-sparing status, race, and marital status were used to evaluate the association of time since RP with two dependent variables: UCLA-PCI-UFS and continence status. Results and limitation The mean UCLA-PCI-UFS declined between 2 yr and 8 yr (83.8 vs 81.8; p = 0.007) and marginally between 8 yr and 10 yr (81.8 vs 79.6; p = 0.036) after RP, whereas continence rate did not significantly change during these intervals. Men ≥60 yr old experienced a decline in mean UCLA-PCI-UFS between 2 yr and 8 yr (p = 0.002) and a marginal decline in continence rate between 2 yr and 10 yr (p = 0.047), whereas these variables did not change significantly in men <60 yr old. These outcomes are for an experienced surgeon, so caution should be exercised in generalizing these results. Conclusions Between 2 yr and 10 yr after RP, there were slight decreases in mean UCLA-PCIUFS and continence rates in this study. Men aged <60 yr had better long-term outcomes. These results provide realistic long-term continence expectations for men undergoing RP. PMID:23957946

  13. 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

  14. 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.

  15. 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

  16. Androgen deprivation therapy in combination with radiotherapy for high-risk clinically localized prostate cancer.

    PubMed

    Nishiyama, Tsutomu

    2012-04-01

    Androgen deprivation therapy (ADT) has remained the main therapeutic option for patients with advanced prostate cancer (PCa) for about 70 years. Several reports and our findings revealed that aggressive PCa can occur under a low dihydrotestosterone (DHT) level environment where the PCa of a low malignancy with high DHT dependency cannot easily occur. Low DHT levels in the prostate with aggressive PCa are probably sufficient to propagate the growth of the tumor, and the prostate with aggressive PCa can produce androgens from the adrenal precursors more autonomously than that with non-aggressive PCa does under the low testosterone environment with testicular suppression. In patients treated with ADT the pituitary-adrenal axis mediated by adrenocorticotropic hormone has a central role in the regulation of androgen synthesis. Several experimental studies have confirmed the potential benefits from the combination of ADT with radiotherapy (RT). A combination of external RT with short-term ADT is recommended based on the results of phase III randomized trials. In contrast, the combination of RT plus 6 months of ADT provides inferior survival as compared with RT plus 3 years of ADT in the treatment of locally advanced PCa. Notably, randomized trials included patients with diverse risk groups treated with older RT modalities, a variety of ADT scheduling and duration and, importantly, suboptimal RT doses. The use of ADT with higher doses of RT or newer RT modalities has to be properly assessed.

  17. 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

  18. 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.

  19. 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.

  20. 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

  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. [The treatment options for localized prostate cancer].

    PubMed

    Livne, Pinhas M

    2006-01-01

    Prostate cancer is a very common tumor in men. Today the disease is very often diagnosed early because of an elevated PSA without symptoms and the disease is localized to the prostate. Patients with prostate cancer can be divided into 3 subgroups for the carcinoma: favorable, moderate, and poorly. The grouping depends mainly on the Gleason score of the prostate biopsy. According to the Gleason score, favorable cancer is up to score 6 (3 + 3), moderate score 7, and poor--Gleason score 8-10. The other favorable clinical factors are PSA < 10 ng/ml, and clinical stage by DRE of T1C or T2 (no nodule or palpable nodule not extending beyond the prostatic capsule). The treatment options for cure when the prostate cancer is localized are either radical prostatectomy or radiotherapy (external or brachytherapy or combination). Each of these therapies has side effects and each has advantages and disadvantages. Sometimes the treatment choice is not for cure and the options are hormonal treatment or watchful waiting. Twenty to 30% of the patients treated for cure may fail the treatment and have elevation of PSA without any clinical symptoms, or signs of local recurrence or distant spread. Some of these patients with biochemical failure may be cured by salvage treatment: radiotherapy after radical prostatectomy and salvage radical prostatectomy or cryotherapy following failure of radiotherapy.

  3. 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.

  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. State-of-the-art radiotherapy in the management of clinically localized prostate carcinoma.

    PubMed

    Bermudez, R Scott; Izaguirre, Alejandra; Roach, Mack

    2007-02-01

    Four Phase III trials demonstrating higher prostate-specific antigen control rates in prostate cancer patients treated with higher doses of radiation have changed the standard of care. Emerging on-line technologies, improved imaging and computer algorithms, combined with an improved understanding of how best to apply them, have allowed radiation oncologists to move ever closer to the optimal application of curative radiation. This technology allows a higher dose to be delivered to tumor-bearing areas while minimizing the dose delivered to surrounding normal tissues. Real-time adaptive techniques have made each step more accurate, and commercialization has increasingly moved these advances further into the community setting. Phase III trials have also helped to define the role of hormonal therapy in combination with radiation and the benefits of prophylactic pelvic nodal radiotherapy in subsets of patients. We have also learnt how to optimize the use of prostate-specific antigen to better determine success and failure following radiotherapy.

  7. Phase II, Randomized, Placebo-Controlled Trial of Neoadjuvant Celecoxib in Men With Clinically Localized Prostate Cancer: Evaluation of Drug-Specific Biomarkers

    PubMed Central

    Antonarakis, Emmanuel S.; Heath, Elisabeth I.; Walczak, Janet R.; Nelson, William G.; Fedor, Helen; De Marzo, Angelo M.; Zahurak, Marianna L.; Piantadosi, Steven; Dannenberg, Andrew J.; Gurganus, Robin T.; Baker, Sharyn D.; Parnes, Howard L.; DeWeese, Theodore L.; Partin, Alan W.; Carducci, Michael A.

    2009-01-01

    Purpose Cyclooxygenase-2 (COX-2) is a potential pharmacologic target for the prevention of various malignancies, including prostate cancer. We conducted a randomized, double-blind trial to examine the effect of celecoxib on drug-specific biomarkers from prostate tissue obtained at prostatectomy. Patients and Methods Patients with localized prostate cancer and Gleason sum ≥ 7, prostate-specific antigen (PSA) ≥ 15 ng/mL, clinical stage T2b or greater, or any combination with greater than 45% risk of capsular penetration were randomly assigned to celecoxib 400 mg by mouth twice daily or placebo for 4 to 6 weeks before prostatectomy. The primary end point was the difference in prostatic prostaglandin levels between the two groups. Secondary end points were differences in COX-1 and -2 expressions; oxidized DNA bases; and markers of proliferation, apoptosis and angiogenesis. Tissue celecoxib concentrations also were measured. Tertiary end points were drug safety and compliance. Results Seventy-three patients consented, and 64 were randomly assigned and included in the intention-to-treat analysis. There were no treatment differences in any of the primary or secondary outcomes. Multivariable regression revealed that tumor tissue had significantly lower COX-2 expression than benign prostatic tissue (P = .01) and significantly higher levels of the proliferation marker Ki-67 (P < .0001). Celecoxib was measurable in prostate tissue of patients on treatment, demonstrating that celecoxib reached its target. Celecoxib was safe and resulted in only grade 1 toxicities. Conclusion Treatment with 4 to 6 weeks of celecoxib had no effect on intermediate biomarkers of prostate carcinogenesis, despite the achievement of measurable tissue levels. We caution against using celecoxib 400 mg twice daily as a preventive agent for prostate cancer in additional studies. PMID:19720908

  8. ACR Appropriateness Criteria® external-beam radiation therapy treatment planning for clinically localized prostate cancer.

    PubMed

    Abdel-Wahab, May; Mahmoud, Omar; Merrick, Gregory; Hsu, I-Chow Joe; Arterbery, V Elayne; Ciezki, Jay P; Frank, Steven J; Mohler, James Lloyd; Moran, Brian J; Rosenthal, Seth A; Rossi, Carl J; Yamada, Yoshiya

    2012-04-01

    Image-based radiation treatment planning and localization have contributed to better targeting of the prostate and sparing of normal tissues. Guidelines are needed to address radiation dose delivery, including patient setup and immobilization, target volume definition, treatment planning, treatment delivery methods, and target localization. Guidelines for external-beam radiation treatment planning have been updated and are presented here. The use of appropriate doses, simulation techniques, and verification of field setup are essential for the accurate delivery of radiation therapy. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

  9. Prostatitis

    PubMed Central

    Domingue, Gerald J.; Hellstrom, Wayne J. G.

    1998-01-01

    The laboratory diagnosis of acute bacterial prostatitis is straightforward and easily accomplished in clinical laboratories. Chronic bacterial prostatitis, and especially chronic idiopathic prostatitis (most often referred to as abacterial prostatitis), presents a real challenge to the clinician and clinical microbiologist. Clinically, the diagnosis of chronic idiopathic prostatitis is differentiated from that of acute prostatitis by a lack of prostatic inflammation and no “significant” (controversial) leukocytes or bacteria in the expressed prostatic secretions. Despite these diagnostic criteria, the etiology of chronic idiopathic prostatitis is unknown. While this review covers the entire spectrum of microbially caused acute prostatitis (including common and uncommon bacteria, viruses, fungi, and parasites) and microbially associated chronic prostatitis, a special focus has been given to chronic idiopathic prostatitis. The idiopathic syndrome is commonly diagnosed in men but is poorly treated. Recent data convincingly suggests a possible bacterial etiology for the condition. Provocative molecular studies have been published reporting the presence of 16S rRNA bacterial sequences in prostate biopsy tissue that is negative for ordinary bacteria by routine culture in men with chronic idiopathic prostatitis. Additionally, special culture methods have indicated that difficult-to-culture coryneforms and coagulase-negative staphylococci are present in expressed prostatic secretions found to be negative by routine culture techniques. Treatment failures are not uncommon in chronic prostatitis. Literature reports suggest that antimicrobial treatment failures in chronic idiopathic prostatitis caused by organisms producing extracellular slime might result from the virulent properties of coagulase-negative staphylococci or other bacteria. While it is difficult to definitively extrapolate from animal models, antibiotic pharmokinetic studies with a murine model have

  10. Proton radiation for localized prostate cancer.

    PubMed

    Coen, John J; Zietman, Anthony L

    2009-06-01

    Proton radiation is an emerging therapy for localized prostate cancer that is being sought with increasing frequency by patients. The physical properties of a proton beam make it ideal for clinical applications; the Bragg peak allows for deposition of dose at a well-defined depth with essentially no exit dose. Thus, high doses can be delivered to a target while largely sparing adjacent normal tissue. Proton radiation has proven effective in dose escalation for prostate cancer. This is important, as high-dose conformal radiation is now the standard form of external radiation for this disease. Intensity-modulated radiation therapy, which uses X-rays, is another means of delivering high radiation doses to the prostate and is currently the most widely used form of external radiation in the US. At present prices, it is probably more cost-effective than proton radiation; this could change. Clear dosimetric superiority of protons in the high-dose region has not yet been demonstrated. A dosimetric advantage may emerge as pencil-beam scanning replaces passive scanning, and intensity-modulated proton therapy becomes possible. This technique would be particularly well suited to partial prostate 'boosts', hypofractionation regimens and stereotactic delivery of radiation, all new approaches to prostate cancer that are being investigated.

  11. Multi-institutional clinical experience with the Calypso System in localization and continuous, real-time monitoring of the prostate gland during external radiotherapy

    SciTech Connect

    Kupelian, Patrick . E-mail: patrick.kupelian@orhs.org; Willoughby, Twyla; Mahadevan, Arul; Djemil, Toufik; Weinstein, Geoffrey; Jani, Shirish; Enke, Charles; Solberg, Timothy; Flores, Nicholas

    2007-03-15

    Purpose: To report the clinical experience with an electromagnetic treatment target positioning and continuous monitoring system in patients with localized prostate cancer receiving external beam radiotherapy. Methods and Materials: The Calypso System is a target positioning device that continuously monitors the location of three implanted electromagnetic transponders at a rate of 10 Hz. The system was used at five centers to position 41 patients over a full course of therapy. Electromagnetic positioning was compared to setup using skin marks and to stereoscopic X-ray localization of the transponders. Continuous monitoring was performed in 35 patients. Results: The difference between skin mark vs. the Calypso System alignment was found to be >5 mm in vector length in more than 75% of fractions. Comparisons between the Calypso System and X-ray localization showed good agreement. Qualitatively, the continuous motion was unpredictable and varied from persistent drift to transient rapid movements. Displacements {>=}3 and {>=}5 mm for cumulative durations of at least 30 s were observed during 41% and 15% of sessions. In individual patients, the number of fractions with displacements {>=}3 mm ranged from 3% to 87%; whereas the number of fractions with displacements {>=}5 mm ranged from 0% to 56%. Conclusion: The Calypso System is a clinically efficient and objective localization method for positioning prostate patients undergoing radiotherapy. Initial treatment setup can be performed rapidly, accurately, and objectively before radiation delivery. The extent and frequency of prostate motion during radiotherapy delivery can be easily monitored and used for motion management.

  12. Development of a Phase I/II Clinical Trial Using Sterotactic Body Radiation Therapy (SBRT) for the Treatment of Localized Prostate Carcinoma

    DTIC Science & Technology

    2006-07-01

    Therapy (SBRT) for Low and Intermediate Risk Prostate Cancer ELIGIBILITY...Cavanagh W, Butler W. I-125 versus Pd-103 for low- risk prostate cancer : long-term morbidity outcomes fom a prospective randomized multicenter...STEREOTACTIC BODY RADIATION THERAPY (SBRT) FOR LOW AND INTERMEDIATE RISK PROSTATE CANCER This is a clinical trial (a type of research study).

  13. Clinical adenoviral gene therapy for prostate cancer.

    PubMed

    Schenk, Ellen; Essand, Magnus; Bangma, Chris H; Barber, Chris; Behr, Jean-Paul; Briggs, Simon; Carlisle, Robert; Cheng, Wing-Shing; Danielsson, Angelika; Dautzenberg, Iris J C; Dzojic, Helena; Erbacher, Patrick; Fisher, Kerry; Frazier, April; Georgopoulos, Lindsay J; Hoeben, Rob; Kochanek, Stefan; Koppers-Lalic, Daniela; Kraaij, Robert; Kreppel, Florian; Lindholm, Leif; Magnusson, Maria; Maitland, Norman; Neuberg, Patrick; Nilsson, Berith; Ogris, Manfred; Remy, Jean-Serge; Scaife, Michelle; Schooten, Erik; Seymour, Len; Totterman, Thomas; Uil, Taco G; Ulbrich, Karel; Veldhoven-Zweistra, Joke L M; de Vrij, Jeroen; van Weerden, Wytske; Wagner, Ernst; Willemsen, Ralph

    2010-07-01

    Prostate cancer is at present the most common malignancy in men in the Western world. When localized to the prostate, this disease can be treated by curative therapy such as surgery and radiotherapy. However, a substantial number of patients experience a recurrence, resulting in spreading of tumor cells to other parts of the body. In this advanced stage of the disease only palliative treatment is available. Therefore, there is a clear clinical need for new treatment modalities that can, on the one hand, enhance the cure rate of primary therapy for localized prostate cancer and, on the other hand, improve the treatment of metastasized disease. Gene therapy is now being explored in the clinic as a treatment option for the various stages of prostate cancer. Current clinical experiences are based predominantly on trials with adenoviral vectors. As the first of a trilogy of reviews on the state of the art and future prospects of gene therapy in prostate cancer, this review focuses on the clinical experiences and progress of adenovirus-mediated gene therapy for this disease.

  14. 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.

  15. Can the conventional sextant prostate biopsy accurately predict unilateral prostate cancer in low-risk, localized, prostate cancer?

    PubMed

    Mayes, Janice M; Mouraviev, Vladimir; Sun, Leon; Tsivian, Matvey; Madden, John F; Polascik, Thomas J

    2011-01-01

    We evaluate the reliability of routine sextant prostate biopsy to detect unilateral lesions. A total of 365 men with complete records including all clinical and pathologic variables who underwent a preoperative sextant biopsy and subsequent radical prostatectomy (RP) for clinically localized prostate cancer at our medical center between January 1996 and December 2006 were identified. When the sextant biopsy detects unilateral disease, according to RP results, the NPV is high (91%) with a low false negative rate (9%). However, the sextant biopsy has a PPV of 28% with a high false positive rate (72%). Therefore, a routine sextant prostate biopsy cannot provide reliable, accurate information about the unilaterality of tumor lesion(s).

  16. Genomic hallmarks of localized, non-indolent prostate cancer.

    PubMed

    Fraser, Michael; Sabelnykova, Veronica Y; Yamaguchi, Takafumi N; Heisler, Lawrence E; Livingstone, Julie; Huang, Vincent; Shiah, Yu-Jia; Yousif, Fouad; Lin, Xihui; Masella, Andre P; Fox, Natalie S; Xie, Michael; Prokopec, Stephenie D; Berlin, Alejandro; Lalonde, Emilie; Ahmed, Musaddeque; Trudel, Dominique; Luo, Xuemei; Beck, Timothy A; Meng, Alice; Zhang, Junyan; D'Costa, Alister; Denroche, Robert E; Kong, Haiying; Espiritu, Shadrielle Melijah G; Chua, Melvin L K; Wong, Ada; Chong, Taryne; Sam, Michelle; Johns, Jeremy; Timms, Lee; Buchner, Nicholas B; Orain, Michèle; Picard, Valérie; Hovington, Helène; Murison, Alexander; Kron, Ken; Harding, Nicholas J; P'ng, Christine; Houlahan, Kathleen E; Chu, Kenneth C; Lo, Bryan; Nguyen, Francis; Li, Constance H; Sun, Ren X; de Borja, Richard; Cooper, Christopher I; Hopkins, Julia F; Govind, Shaylan K; Fung, Clement; Waggott, Daryl; Green, Jeffrey; Haider, Syed; Chan-Seng-Yue, Michelle A; Jung, Esther; Wang, Zhiyuan; Bergeron, Alain; Pra, Alan Dal; Lacombe, Louis; Collins, Colin C; Sahinalp, Cenk; Lupien, Mathieu; Fleshner, Neil E; He, Housheng H; Fradet, Yves; Tetu, Bernard; van der Kwast, Theodorus; McPherson, John D; Bristow, Robert G; Boutros, Paul C

    2017-01-19

    Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates.

  17. The Prostate Health Index Selectively Identifies Clinically Significant Prostate Cancer

    PubMed Central

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

    2015-01-01

    Purpose The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. We investigate whether phi improves specificity for detecting clinically significant prostate cancer and can help reduce prostate cancer over diagnosis. Materials and Methods From a multicenter prospective trial we identified 658 men age 50 years or older with prostate specific antigen 4 to 10 ng/ml and normal digital rectal examination who underwent prostate biopsy. In this population we compared the performance of prostate specific antigen, % free prostate specific antigen, [-2]proPSA and phi to predict biopsy results and, specifically, the presence of clinically significant prostate cancer using multiple criteria. Results The Prostate Health Index was significantly higher in men with Gleason 7 or greater and “Epstein significant” cancer. On receiver operating characteristic analysis phi had the highest AUC for overall cancer (AUCs phi 0.708, percent free prostate specific antigen 0.648, [-2]proPSA 0.550 and prostate specific antigen 0.516), Gleason 7 or greater (AUCs phi 0.707, percent free prostate specific antigen 0.661, [-2]proPSA 0.558, prostate specific antigen 0.551) and significant cancer (AUCs phi 0.698, percent free prostate specific antigen 0.654, [-2]proPSA 0.550, prostate specific antigen 0.549). At the 90% sensitivity cut point for phi (a score less than 28.6) 30.1% of patients could have been spared an unnecessary biopsy for benign disease or insignificant prostate cancer compared to 21.7% using percent free prostate specific antigen. Conclusions The new phi test outperforms its individual components of total, free and [-2]proPSA for the identification of clinically significant prostate cancer. Phi may be useful as part of a multivariable approach to reduce prostate biopsies and over diagnosis. PMID:25463993

  18. 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.

  19. Current clinical challenges in prostate cancer

    PubMed Central

    Silberstein, Jonathan L.; Pal, Sumanta Kumar; Lewis, Brian

    2013-01-01

    Prostate cancer is the most common malignancy and the second leading cause of cancer death in men in the United States. Close to $12 billion are spent annually on the treatment of prostate cancer in the US alone. Yet still there remain tremendous controversies and challenges that exist in all facets of the disease. This review and discussion will focus on issues and challenges for clinicians and patients diagnosed with the disease. Appropriate risk stratification for men with newly diagnosed prostate cancer is an appropriate first step for all patients. Once risk-stratified, for those with low-risk of death, it is increasingly recognized that overtreatment creates an unnecessary burden for many patients. This is particularly evident when put in the context of competing comorbidities in an elderly population. For those with advanced or high-risk localized disease, under-treatment remains too common. For those with a high-risk of recurrence or failure following primary treatment, adjuvant or salvage therapies are an option, but how and when to best deploy these treatments are controversial. Recently, tremendous progress has been made for those with advanced disease, in particular those with metastatic castrate-resistant prostate cancer (mCRPC). Within the last 4 years, five novel FDA approved agents, acting through distinct mechanisms have been FDA approved for mCRPC. With the introduction of these new agents a host of new challenges have arisen. Timing, sequencing and combinations of these novel agents are welcomed challenges when compared with the lack of available therapies just a few years ago. In this summary of current clinical challenges in prostate cancer we review critical recent studies that have created or shifted the current paradigms of treatment for prostate cancer. We will also highlight ongoing issues that continue to challenge our field. PMID:26816735

  20. Androgen deprivation therapy in the treatment of locally advanced, nonmetastatic prostate cancer: practical experience and a review of the clinical trial evidence

    PubMed Central

    Aoun, Fouad; Bourgi, Ali; Ayoub, Elias; El Rassy, Elie; van Velthoven, Roland; Peltier, Alexandre

    2017-01-01

    Following new scientific insights, initial management for patients with high-risk nonmetastatic prostate cancer has changed considerably and rapidly over the last few years. Several clinical and pathologic variables should be taken into account when deciding the best treatment choice for those patients. These variables are summarized and discussed in detail. High radiation doses to the prostate are essential to achieve good local control in patients with high-risk nonmetastatic disease. Addition of androgen deprivation therapy (ADT) to radiation therapy has significantly improved overall survival and cancer-specific survival compared with radiation therapy alone without significantly increasing toxicity. Long-term neo(adjuvant) ADT (2–3 years) to radiation therapy significantly improved cancer-specific survival compared with short-term ADT (4–6 months). Radical prostatectomy with extended pelvic lymph node dissection is considered a reasonable option in experienced hands. ADT alone is an inappropriate treatment option for patients with high-risk nonmetastatic disease. Management decisions for these patients should be discussed by a multidisciplinary team. PMID:28392836

  1. 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.

  2. 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

  3. Thermal dosimetry analysis combined with patient-specific thermal modeling of clinical interstitial ultrasound hyperthermia integrated within HDR brachytherapy for treatment of locally advanced prostate cancer

    NASA Astrophysics Data System (ADS)

    Salgaonkar, Vasant A.; Wootton, Jeff; Prakash, Punit; Scott, Serena; Hsu, I. C.; Diederich, Chris J.

    2017-03-01

    This study presents thermal dosimetry analysis from clinical treatments where ultrasound hyperthermia (HT) was administered following high-dose rate (HDR) brachytherapy treatment for locally advanced prostate cancer as part of a clinical pilot study. HT was administered using ultrasound applicators from within multiple 13-g brachytherapy catheters implanted along the posterior periphery of the prostate. The heating applicators were linear arrays of sectored tubular transducers (˜7 MHz), with independently powered array elements enabling energy deposition with 3D spatial control. Typical heat treatments employed time-averaged peak acoustic intensities of 1 - 3 W/cm2 and lasted for 60 - 70 minutes. Throughout the treatments, temperatures at multiple points were monitored using multi-junction thermocouples, placed within available brachytherapy catheters throughout mid-gland prostate and identified as the hyperthermia target volume (HTV). Clinical constraints allowed placement of 8 - 12 thermocouple sensors in the HTV and patient-specific 3D thermal modeling based on finite element methods (FEM) was used to supplement limited thermometry. Patient anatomy, heating device positions, orientations, and thermometry junction locations were obtained from patient CT scans and HDR and hyperthermia planning software. The numerical models utilized the applied power levels recorded during the treatments. Tissue properties such as perfusion and acoustic absorption were varied within physiological ranges such that squared-errors between measured and simulated temperatures were minimized. This data-fitting was utilized for 6 HT treatments to estimate volumetric temperature distributions achieved in the HTV and surrounding anatomy devoid of thermocouples. For these treatments, the measured and simulated T50 values in the hyperthermia target volume (HTV) were between 40.1 - 43.9 °C and 40.3 - 44.9 °C, respectively. Maximum temperatures between 46.8 - 49.8 °C were measured during

  4. 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

  5. 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.

  6. 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

  7. Prostate cancer vaccines in clinical trials.

    PubMed

    Lubaroff, David M

    2012-07-01

    This review presents important information about the current state of the art for vaccine immunotherapy of prostate cancer. It includes important preclinical research for each of the important prostate cancer vaccines to have reached clinical trials. To date, the only prostate cancer vaccine that has completed Phase III trials and has been approved and licensed by the US FDA is Sipuleucel-T, which immunizes patients against the prostate-associated antigen prostatic acid phosphatase. The benefits and concerns associated with the vaccine are presented. A current Phase III trial is currently underway using the vaccinia-based prostate-specific antigen vaccine Prostvac-TRICOM. Other immunotherapeutic vaccines in trials include the Ad/prostate-specific antigen vaccine Ad5-prostate-specific antigen and the DNA/prostatic acid phosphatase vaccine. A cellular vaccine, GVAX, has been in clinical trials but has not seen continuous study. This review also delves into the multiple immune regulatory elements that must be overcome in order to obtain strong antitumor-associated antigen immune responses capable of effectively destroying prostate tumor cells.

  8. 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

  9. [Locally advanced prostate cancer: definition, prognosis and treatment].

    PubMed

    Plantade, Anne; Massard, Christophe; de Crevoisier, Renaud; Fizazi, Karim

    2007-07-01

    According to d'Amico's criteria, high-risk localized prostate cancer are defined either by an extracapsular extension (T3 or T4), either by a high Gleason score (> 7) or a PSA rate higher than 20 ng/ml. Pelvic lymph node involvement also corresponds to locally advanced prostate cancer. Statistical models called nomograms have been developed to predict the probability of prostate cancer recurrence and are also used to define locally advanced patients. Prostate MRI may help to detect an extracapsular extension or a seminal vesicles involvement but remains still discussed. A bone scan, an abdominal and pelvic CT scan have to be performed in order to detect metastases. A pelvic lymph node dissection is recommended in order to adapt the treatment of these patients. Standard treatment for high-risk localized prostate cancer without lymph node involvement is now well defined. The association of both local radiation and a long androgen deprivation (GnHR agonist) showed an overall survival benefit (more than 10%). The radiation dose of 74 Gy is recommended. Other questions are still debating : the optimal duration of the hormonotherapy , the use of the bicalutamide 150 mg instead of GnRH agonists, the optimal radiation dose. Radical prostatectomy is no more considered as a standard treatment for these patients. Since the use of chemotherapy for metastatic patients showed a benefit in overall survival, the place of chemotherapy as adjuvant or neo-adjuvant treatment is questionned in several randomized phase III studies. Sometimes high-risk disease is diagnosed after performance of a radical prostatectomy. A postoperative radiation may be performed in order to decrease clinical and biochemical progression. The use of bicalutamide 150 mg in this situation may have a positive impact too on progression free survival. In case of lymph node involvement, androgen deprivation is the standard treatment with an overall survival benefit. The place of local radiation therapy is still

  10. 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.

  11. Novel Nuclear Localization of Fatty Acid Synthase Correlates with Prostate Cancer Aggressiveness

    PubMed Central

    Madigan, Allison A.; Rycyna, Kevin J.; Parwani, Anil V.; Datiri, Yeipyeng J.; Basudan, Ahmed M.; Sobek, Kathryn M.; Cummings, Jessica L.; Basse, Per H.; Bacich, Dean J.; O'Keefe, Denise S.

    2015-01-01

    Fatty acid synthase is up-regulated in a variety of cancers, including prostate cancer. Up-regulation of fatty acid synthase not only increases production of fatty acids in tumors but also contributes to the transformed phenotype by conferring growth and survival advantages. In addition, increased fatty acid synthase expression in prostate cancer correlates with poor prognosis, although the mechanism(s) by which this occurs are not completely understood. Because fatty acid synthase is expressed at low levels in normal cells, it is currently a major target for anticancer drug design. Fatty acid synthase is normally found in the cytosol; however, we have discovered that it also localizes to the nucleus in a subset of prostate cancer cells. Analysis of the fatty acid synthase protein sequence indicated the presence of a nuclear localization signal, and subcellular fractionation of LNCaP prostate cancer cells, as well as immunofluorescent confocal microscopy of patient prostate tumor tissue and LNCaPs confirmed nuclear localization of this protein. Finally, immunohistochemical analysis of prostate cancer tissue indicated that nuclear localization of fatty acid synthase correlates with Gleason grade, implicating a potentially novel role in prostate cancer progression. Possible clinical implications include improving the accuracy of prostate biopsies in the diagnosis of low- versus intermediate-risk prostate cancer and the uncovering of novel metabolic pathways for the therapeutic targeting of androgen-independent prostate cancer. PMID:24907642

  12. 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.

  13. 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

  14. [Contemporary methods of treatment in local advanced prostate cancer].

    PubMed

    Brzozowska, Anna; Mazurkiewicz, Maria; Starosławska, Elzbieta; Stasiewicz, Dominika; Mocarska, Agnieszka; Burdan, Franciszek

    2012-10-01

    The prostate cancer is one of the most often cancers amongst males. Its frequency is increasing with age. Thanks to widespread of screening denomination of specific prostate specific antigen (PSA), ultrasonography including the one in transrectal (TRUS), computed tomography, magnetic resonance and especially the awareness of society, the number of patients with low local advance of illness is increasing. The basic method of treatment in such cases is still the surgical removal of prostate with seminal bladder or radiotherapy. To this purpose tele-(IMRT, VMAT) or brachytherapy (J125, Ir192, Pa103) is used. In patients with higher risk of progression the radiotherapy may be associated with hormonotherapy (total androgen blockage-LH-RH analog and androgen). Despite numerous clinical researches conducted there is still no selection of optimal sequence of particular methods. Moreover, no explicit effectiveness was determined. The general rule of treatment in patients suffering from prostate cancer still remains individual selection of therapeutic treatment depending on the age of a patient, general condition and especially patient's general preferences. In case of elderly patients and patients with low risk of progression, recommendation of direct observation including systematical PSA denomination, clinical transrectal examination, TRUS, MR of smaller pelvis or scintigraphy of the whole skeleton may be considered.

  15. Therapeutic Strategies for Localized Prostate Cancer II

    PubMed Central

    Weil, Michael D; Porter, Arthur T; Beyer, David C; Albert, Peter S; Chinn, Douglas; Harris, Michael J

    2000-01-01

    Application of improved imaging, diagnostic, and computer techniques is beginning to have an impact on the management of localized prostate cancer. It is possible to perform a range of surgical and radiation procedures with less morbidity than in the past. The changes in therapy for patients with localized disease derive from better knowledge of anatomy for invasive procedures and optimization of virtual planning for noninvasive methods. Perineal prostatectomy and combinations of beam and seed radiation offer both patient and physician reasonable therapeutic options. PMID:16986038

  16. 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.

  17. Perioperative Search for Circulating Tumor Cells in Patients Undergoing Prostate Brachytherapy for Clinically Nonmetastatic Prostate Cancer

    PubMed Central

    Tsumura, Hideyasu; Satoh, Takefumi; Ishiyama, Hiromichi; Tabata, Ken-ichi; Takenaka, Kouji; Sekiguchi, Akane; Nakamura, Masaki; Kitano, Masashi; Hayakawa, Kazushige; Iwamura, Masatsugu

    2017-01-01

    Despite the absence of local prostate cancer recurrence, some patients develop distant metastases after prostate brachytherapy. We evaluate whether prostate brachytherapy procedures have a potential risk for hematogenous spillage of prostate cancer cells. Fifty-nine patients who were undergoing high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy participated in this prospective study. Thirty patients with high-risk or locally advanced cancer were treated with HDR brachytherapy after neoadjuvant androgen deprivation therapy (ADT). Twenty-nine patients with clinically localized cancer were treated with LDR brachytherapy without neoadjuvant ADT. Samples of peripheral blood were drawn in the operating room before insertion of needles (preoperative) and again immediately after the surgical manipulation (intraoperative). Blood samples of 7.5 mL were analyzed for circulating tumor cells (CTCs) using the CellSearch System. While no preoperative samples showed CTCs (0%), they were detected in intraoperative samples in 7 of the 59 patients (11.8%; preoperative vs. intraoperative, p = 0.012). Positive CTC status did not correlate with perioperative variables, including prostate-specific antigen (PSA) at diagnosis, use of neoadjuvant ADT, type of brachytherapy, Gleason score, and biopsy positive core rate. We detected CTCs from samples immediately after the surgical manipulation. Further study is needed to evaluate whether those CTCs actually can survive and proliferate at distant sites. PMID:28085051

  18. 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.

  19. Radiation, hormonotherapy, survival and local control in prostatic carcinoma.

    PubMed

    Cellini, N; Luzi, S; Morganti, A G; Smaniotto, D; Niespolo, R M; Valentini, V

    1998-01-01

    The combination of concomitant external beam radiotherapy (ERT) and neoadjuvant hormonotherapy was shown to be able to significantly improve local control and disease-free survival in locally advanced prostatic carcinoma. (RTOG study 8610). Aim of this analysis was to assess the clinical results observed in a population of patients undergoing this combined treatment and, more particularly, to examine the prognostic impact of local control. 84 patients (T2: 47%, T3: 49.4%, T4: 3.6%) underwent concomitant ERT (dose to pelvic volume: 45 Gy; mean dose to prostatic volume: 65 Gy) and neoadjuvant hormonotherapy (flutamide: 250 mg three times/daily for 30 days; LH-RH analogue: 1 oral dose every 28 days starting 2 months prior to radiotherapy and for its whole duration). With a median follow-up of 36 months, 3.6% of patients were deceased; hematogenous metastases and local disease progression were recorded in 16.7% and 4.8% of patients, respectively. Local disease progression was shown to be significantly correlated with the incidence of metastases. In fact, the actuarial incidence of metastases at 5 years was 100% and 27% in patients with and without local recurrence (p = 0.0043) respectively. Overall, metastases-free local and biochemical recurrence-free survival was 89.2%, 66.5%, 85.0% and 41.9% respectively. At univariate analysis (logrank) the clinical stage (T) was shown to be significantly correlated with the incidence of metastases (p = .0004) and local progression (p < .0001). In conclusion, this study has confirmed the low rate of local progression with the combination of hormonotherapy and radiotherapy and the significant correlation of local control with the incidence of hematogenous metastases.

  20. WITHDRAWN: Can the conventional sextant prostate biopsy reliably diagnose unilateral prostate cancer in low-risk, localized, prostate cancer?

    PubMed

    Mayes, J M; Mouraviev, V; Sun, L; Madden, J F; Polascik, T J

    2008-05-13

    The authors hereby retract the e-publication dated 13 May 2008 and entitled, 'Can the conventional sextant prostate biopsy reliably diagnose unilateral prostate cancer in low-risk, localized, prostate cancer?' The authors are submitting a revised version with the same title. This article's statistics were performed for predicting bilateral prostate cancer outcomes. The article was written to help predict unilateral prostate cancer. Although the statistical numbers are correct, they are backwards. We apologize that the statistics indicate a contrary outcome (eg predicting bilateral cancer instead of unilateral disease).

  1. Clinical controversies: proton therapy for prostate cancer.

    PubMed

    Mouw, Kent W; Trofimov, Alexei; Zietman, Anthony L; Efstathiou, Jason A

    2013-04-01

    Proton therapy has been used in the treatment of prostate cancer for several decades, and interest surrounding its use continues to grow. Proton-based treatment techniques have evolved significantly over this period, and several centers now routinely use technologies such as pencil-beam scanning. However, whether the theoretical dosimetric advantages of the proton beam translate into clinically meaningful improvements for prostate cancer patients is unknown, and outcomes from single-arm experiences using whole courses of proton beam therapy in the treatment of early-stage prostate cancer have shown mixed results when compared with contemporary intensity-modulated radiotherapy. A randomized trial comparing proton beam therapy with intensity-modulated radiotherapy in early-stage disease has been launched and will be important in defining the role for proton therapy in this setting. We review the available evidence and present the current state of proton beam therapy for prostate cancer.

  2. The ratio of oleic-to-stearic acid in the prostate predicts biochemical failure after radical prostatectomy for localized prostate cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our study examined lifestyle-related factors that may influence the prognosis of clinically localized prostate cancer, we evaluated the relative impact of obesity and prostatic fatty acid concentrations at diagnosis on risk of biochemical failure following radical prostatectomy. Height and weight w...

  3. Vascular-targeted photodynamic of prostate cancer phase with Tookad for recurrent prostate cancer following radiation therapy: initial clinical studies

    NASA Astrophysics Data System (ADS)

    Weersink, Robert A.; Wilson, Brian C.; Bogaards, Arjen; Gertner, Mark R.; Davidson, Sean R. H.; Haider, Masoom A.; Elhilali, Mostafa; Trachtenberg, John

    2007-02-01

    We report on the first clinical application of vascular-targeted photodynamic therapy using a bacteriopheophorbide derivative, Tookad, in patients with localized prostate cancer following external beam radiation therapy. Patients received either escalating intravenous drug doses at a fixed light dose or escalated light doses at the highest photosensitizer dose. Two cylindrically diffusing fibers were placed transperineally in the prostate, along with light monitoring fibers in the prostate, urethra and rectum. Treatment response was assessed with 7-day gadolinium-enhanced T1-weighted MRI and 6-month biopsy. Lesion formation was strongly drug and light dose-dependent, with an apparent threshold response. Early biochemical and MRI responses support the clinical potential of TOOKAD-PDT to treat locally-recurrent prostate cancer.

  4. Watchful waiting and active surveillance approach in patients with low risk localized prostatic cancer: an experience of out-patients clinic with 12-year follow-up.

    PubMed

    Kravchick, Sergey; Peled, Ronit; Cytron, Shmuel

    2011-12-01

    In this study we evaluated the safety of expectant approach in the patients with low risk prostate cancer in the reality of community based out-patients clinics. 48 men were enrolled into the study. The inclusion criteria were age ranged from 60 to 75 years and the Epstein criteria for low risk prostate cancer. Patients were managed expectantly while curative treatment was offered when indicated. Initial and final Charlson comorbidity index (CCI) and BMI were assessed for all men. Patients' median follow-up was 81.1 ± 29.1 years. During this study 41.7% of the patients chose active forms of treatment. Cancer was found in 20.8% (n-10) of our patients. Two first sessions of re-biopsy diagnosed 92% of T1c upgrading. Six men with CCI ≥2 died from concomitant disease and no one died from PCa. Significant correlation was found between BMI and final CCI ≥2 (p-0.001). Expectant approach can be considered as self alternative to active treatment model in selected group of patients with well differentiated PCa, however 20.8% of these patients are still at risk of having aggressive form of cancer. Expectant approach is particular beneficial for the patients with CCI 1-2 and high BMI.

  5. Outcomes of active surveillance for the management of clinically localized prostate cancer in the prospective, multi-institutional Canary PASS cohort

    PubMed Central

    Newcomb, Lisa F.; Thompson, Ian M.; Boyer, Hilary D.; Brooks, James D.; Carroll, Peter R.; Cooperberg, Matthew R.; Dash, Atreya; Ellis, William J.; Fazli, Ladan; Feng, Ziding; Gleave, Martin E.; Kunju, Priya; Lance, Raymond S.; McKenney, Jesse K.; Meng, Maxwell V.; Nicolas, Marlo M.; Sanda, Martin G.; Simko, Jeffry; So, Alan; Tretiakova, Maria S.; Troyer, Dean A.; True, Lawrence D.; Vakar-Lopez, Funda; Virgin, Jeff; Wagner, Andrew A.; Wei, John T.; Zheng, Yingye; Nelson, Peter S.; Lin, Daniel W.

    2016-01-01

    Purpose Active surveillance represents a strategy to address the overtreatment of prostate cancer, yet uncertainty regarding individual patient outcomes remains a concern. We evaluated outcomes in a prospective multi-center study of active surveillance. Methods We studied 905 men in the prospective Canary Prostate cancer Active Surveillance Study (PASS) enrolled between 2008 to 2013. We collected clinical data at study entry and at pre-specified intervals and determined associations with adverse reclassification defined as increased Gleason grade or greater cancer volume on follow-up biopsy. We also evaluated the relationships of clinical parameters with pathology findings in participants who underwent surgery after a period of active surveillance. Results During a median follow-up of 28 months, 24% of participants experienced adverse reclassification, of whom 53% underwent treatment while 31% continued active surveillance. Overall, 19% of participants received treatment, 68% with adverse reclassification while 32% opted for treatment without disease reclassification. In multivariate Cox proportional hazards modeling, percent of biopsy cores with cancer, BMI, and PSA density were associated with adverse reclassification (P = 0.01, 0.04, 0.04). Of 103 participants subsequently treated by radical prostatectomy, 34% had adverse pathology, defined as primary pattern 4–5 or non-organ confined disease, including two with positive lymph nodes, with no significant relationship between risk category at diagnosis and findings at surgery (P = 0.76). Conclusion Most men remain on active surveillance at five years without adverse reclassification or adverse pathology at surgery. However, clinical factors had only modest association with disease reclassification, supporting the need for approaches that improve prediction of this outcome. PMID:26327354

  6. Radiologic presentation of chronic granulomatous prostatitis mimicking locally advanced prostate adenocarcinoma.

    PubMed

    Lee, Su-Min; Joshi, Jay; Wolfe, Konrad; Acher, Peter; Liyanage, Sidath H

    2016-06-01

    We present a case of nonspecific granulomatous prostatitis (GP), a clinical mimic of prostate adenocarcinoma. A 54-year-old man presented with lower urinary tract symptoms and raised prostate-specific antigen. Magnetic resonance imaging showed features consistent with prostate cancer, including low T2-signal intensity in the peripheral and transition zones with signs of extracapsular extension. Diffusion-weighted imaging showed high-signal intensity, with low apparent diffusion coefficient values, whereas dynamic contrast enhancement demonstrated a type 3 washout curve, similar to that found in prostate cancer. Transperineal sector-guided prostate biopsy confirmed nonspecific GP, and the patient was treated conservatively. We discuss and compare nonspecific, chronic GP as a radiologic mimic of prostate adenocarcinoma patient.

  7. 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.

  8. Early Choline Levels From 3-Tesla MR Spectroscopy After Exclusive Radiation Therapy in Patients With Clinically Localized Prostate Cancer are Predictive of Plasmatic Levels of PSA at 1 Year

    SciTech Connect

    Crehange, Gilles; Maingon, Philippe; Gauthier, Melanie; Parfait, Sebastien; Cochet, Alexandre; Mirjolet, Celine; Bonnetain, Franck; Cormier, Luc; Brunotte, Francois; Walker, Paul

    2011-11-15

    Purpose: To investigate the time course response of prostate metabolism to irradiation using magnetic resonance spectroscopy (MRS) at 3-month intervals and its impact on biochemical control. Methods and Materials: Between January 2008 and April 2010, 24 patients with localized prostate cancer were prospectively enrolled in the Evaluation of the Response to Irradiation with MR Spectroscopy (ERIS) trial. All the patients had been treated with intensity-modulated radiation therapy with or without long-term adjuvant hormonal therapy (LTHT) and underwent 3-T MRS and prostate-specific antigen (PSA) assays at baseline and every 3 months thereafter up to 12 months. Results: After radiation, the mean normalized citrate level (citrate/water) decreased significantly over time, both in the peripheral zone (PZ) (p = 0.0034) and in the entire prostate (p = 0.0008), whereas no significant change was observed in mean normalized choline levels (choline/water) in the PZ (p = 0.84) and in the entire prostate (p = 0.95). At 6 months after radiation, the mean choline level was significantly lower in the PZ for patients with a PSA value of {<=}0.5 ng/mL at 12 months (4.9 {+-} 1.7 vs. 7.1 {+-} 1.5, p = 0.0378). Similar results were observed at 12 months in the PZ (6.2 {+-} 2.3 vs. 11.4 {+-} 4.1, p = 0.0117 for choline level and 3.4 {+-} 0.7 vs. 16.1 {+-} 6.1, p = 0.0054 for citrate level) and also in the entire prostate (6.2 {+-} 1.9 vs. 10.4 {+-} 3.2, p = 0.014 for choline level and 3.0 {+-} 0.8 vs. 13.3 {+-} 4.7, p = 0.0054 for citrate level). For patients receiving LTHT, there was no correlation between choline or citrate levels and PSA value, either at baseline or at follow-up. Conclusions: Low normalized choline in the PZ, 6 months after radiation, predicts which patients attained a PSA {<=}0.5 ng/mL at 1 year. Further analyses with longer follow-up times are warranted to determine whether or not these new biomarkers can conclusively predict the early radiation response and the

  9. 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.

  10. 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.

  11. Clinical value of prostate segmentation and volume determination on MRI in benign prostatic hyperplasia.

    PubMed

    Garvey, Brian; Türkbey, Barış; Truong, Hong; Bernardo, Marcelino; Periaswamy, Senthil; Choyke, Peter L

    2014-01-01

    Benign prostatic hyperplasia (BPH) is a nonmalignant pathological enlargement of the prostate, which occurs primarily in the transitional zone. BPH is highly prevalent and is a major cause of lower urinary tract symptoms in aging males, although there is no direct relationship between prostate volume and symptom severity. The progression of BPH can be quantified by measuring the volumes of the whole prostate and its zones, based on image segmentation on magnetic resonance imaging. Prostate volume determination via segmentation is a useful measure for patients undergoing therapy for BPH. However, prostate segmentation is not widely used due to the excessive time required for even experts to manually map the margins of the prostate. Here, we review and compare new methods of prostate volume segmentation using both manual and automated methods, including the ellipsoid formula, manual planimetry, and semiautomated and fully automated segmentation approaches. We highlight the utility of prostate segmentation in the clinical context of assessing BPH.

  12. 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.

  13. 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.

  14. Prostate cancer epigenetics and its clinical implications.

    PubMed

    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.

  15. 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

  16. Increasing Sustained Participation in Free Mass Prostate Cancer Screening Clinics

    DTIC Science & Technology

    2005-05-01

    Prostate - Screening Clinic? If I had signs of prostate cancer I wanted to find out so - Newspaper that treatment decisions can be made early ...three study years. 15. SUBJECT TERMS Prostate Cancer, Screening, Early Detection, African Americans 16. SECURITY CLASSIFICATION OF: 17. LIMITATION 18...prostate cancer screening and early detection. Pastors who participated in a focus group in Year I continue to be contacted, and we continue to follow-up

  17. Integrative clinical genomics of advanced prostate cancer

    PubMed Central

    Dan, Robinson; Van Allen, Eliezer M.; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J.; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim M.; Bradley, Robert K.; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P.; Hussain, Maha; Feng, Felix Y.; Tomlins, Scott A.; Cooney, Kathleen A.; Smith, David C.; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E.; Morris, Michael J.; Solomon, Stephen B.; Durack, Jeremy C.; Reuter, Victor E.; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T.; Bowden, Michaela; Balk, Stephen P.; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y.; Mostaghel, Elahe A.; Cheng, Heather H.; Mulcahy, Hyojeong; True, Lawrence D.; Plymate, Stephen R.; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Lopez, Raquel Perez; Demichelis, Francesca; Robinson, Brian D.; Schiffman, Marc A.; Nanus, David M.; Tagawa, Scott T.; Sigaras, Alexandros; Eng, Kenneth W.; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I.; Scher, Howard I.; Pienta, Kenneth J.; Kantoff, Philip; de Bono, Johann S.; Rubin, Mark A.; Nelson, Peter S.; Garraway, Levi A.; Sawyers, Charles L.; Chinnaiyan, Arul M.

    2015-01-01

    SUMMARY Toward development of a precision medicine framework for metastatic, castration resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53 and PTEN were frequent (40–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified novel genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin and ZBTB16/PLZF. Aberrations of BRCA2, BRCA1 and ATM were observed at substantially higher frequencies (19.3% overall) than seen in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides evidence that clinical sequencing in mCRPC is feasible and could impact treatment decisions in significant numbers of affected individuals. PMID:26000489

  18. 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.

  19. 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

  20. Optimal management of prostate cancer with lethal biology--state-of-the-art local therapy.

    PubMed

    Chapin, Brian F

    2015-01-01

    Defining prostate cancer with lethal biology based upon clinical criteria is challenging. Locally advanced/High-Grade prostate cancer can be downstaged or even downgraded with cure in up to 60% of patients with primary therapy. However, what is known is that high-grade prostate cancers have a greater potential for recurrence and progression to metastatic disease, which can ultimately result in a patient's death. Patients with clinical features of "high-risk" prostate cancer (cT2c, PSA >20, ≥ Gl 8 on biopsy) are more likely to harbor more aggressive pathologic findings. The optimal management of high-risk prostate cancer is not known as there are not prospective studies comparing surgery to radiation therapy (RT). Retrospective and population-based studies are subject to many biases and attempts to compare surgery and radiation have demonstrated mixed results. Some show equivalent survival outcomes while others showing an advantage of surgery over RT. Local therapy for high-risk disease does appear to be beneficial. Improved outcomes realized with local therapy have been clearly demonstrated by several prospective studies evaluating androgen deprivation therapy (ADT) alone versus ADT plus RT. The combination of local with systemic treatment showed improved disease-specific and overall survival outcomes. Unfortunately, primary ADT for N0M0 prostate cancer is still inappropriately applied in general practice. While the surgical literature is largely retrospective, it too demonstrates that surgery in the setting of high-risk prostate cancer is effective in providing durable disease-specific and overall survivals. [

  1. Very high risk localized prostate cancer: definition and outcomes

    PubMed Central

    Sundi, Debasish; Wang, Vinson M.; Pierorazio, Phillip M.; Han, Misop; Bivalacqua, Trinity J.; Ball, Mark W.; Antonarakis, Emmanuel S.; Partin, Alan W.; Schaeffer, Edward M.; Ross, Ashley E.

    2013-01-01

    Purpose Outcomes in men with NCCN high-risk prostate cancer (PCa) can vary substantially--some will have excellent cancer-specific survival, whereas others will experience early metastasis even after aggressive local treatments. Current nomograms, which yield continuous risk probabilities, do not separate high-risk PCa into distinct sub-strata. Here we derive a binary definition of very-high-risk (VHR) localized PCa to aid in risk stratification at diagnosis and selection of therapy. Materials and Methods We queried the Johns Hopkins radical prostatectomy database to identify 753 men with NCCN high-risk localized PCa (Gleason sum 8–10, PSA >20 ng/ml, or clinical stage ≥T3). 28 alternate permutations of adverse grade, stage, and cancer volume were compared by their hazard ratios for metastasis and cancer-specific mortality. VHR criteria with top-ranking hazard ratios were further evaluated by multivariable analyses and inclusion of a clinically meaningful proportion of the high-risk cohort. Results The VHR cohort was best defined by primary pattern 5 present on biopsy, or ≥5 cores with Gleason sum 8–10, or multiple NCCN high-risk features. These criteria encompassed 15.1% of the NCCN high-risk cohort. Compared to other high-risk men, VHR men were at significantly higher risk for metastasis (H.R. 2.75) and cancer-specific mortality (H.R. 3.44) (p <0.001 for both). Among high-risk men, VHR men also had significantly worse 10-year metastasis-free survival (37% vs 78%) and cancer-specific survival (62% vs 90%). Conclusions Men who meet VHR criteria form a subgroup within the current NCCN high-risk classification who have particularly poor oncologic outcomes. Use of these characteristics to distinguish VHR localized PCa may help in counseling and selection optimal candidates for multimodal treatments or clinical trials. PMID:24189998

  2. Clinical and Dosimetric Predictors of Late Rectal Syndrome After 3D-CRT for Localized Prostate Cancer: Preliminary Results of a Multicenter Prospective Study

    SciTech Connect

    Fiorino, Claudio Fellin, Gianni; Rancati, Tiziana; Vavassori, Vittorio; Bianchi, Carla; Borca, Valeria Casanova; Girelli, Giuseppe; Mapelli, Marco; Menegotti, Loris; Nava, Simona; Valdagni, Riccardo

    2008-03-15

    Purpose: To assess the predictors of late rectal toxicity in a prospectively investigated group of patients treated at 70-80 Gy for prostate cancer (1.8-2 Gy fractions) with three-dimensional conformal radiotherapy. Methods and Materials: A total of 1,132 patients were entered into the study between 2002 and 2004. Three types of rectal toxicity, evaluated by a self-administered questionnaire, mainly based on the subjective objective management, analytic late effects of normal tissue system, were considered: stool frequency/tenesmus/pain, fecal incontinence, and bleeding. The data from 506 patients with a follow-up of 24 months were analyzed. The correlation between a number of clinical and dosimetric parameters and Grade 2 or greater toxicity was investigated by univariate and multivariate (MVA) logistic analyses. Results: Of the 1,132 patients, 21, 15, and 30 developed stool frequency/tenesmus/pain, fecal incontinence, and bleeding, respectively. Stool frequency/tenesmus/pain correlated with previous abdominal/pelvic surgery (MVA, p = 0.05, odds ratio [OR], 3.3). With regard to incontinence, MVA showed the volume receiving {>=}40 Gy (V{sub 40}) (p = 0.035, OR, 1.037) and surgery (p = 0.02, OR, 4.4) to be the strongest predictors. V{sub 40} to V{sub 70} were highly predictive of bleeding; V{sub 70} showed the strongest impact on MVA (p = 0.03), together with surgery (p = 0.06, OR, 2.5), which was also the main predictor of Grade 3 bleeding (p = 0.02, OR, 4.2). Conclusions: The predictive value of the dose-volume histogram was confirmed for bleeding, consistent with previously suggested constraints (V{sub 50} <55%, V{sub 60} <40%, V{sub 70} <25%, and V{sub 75} <5%). A dose-volume histogram constraint for incontinence can be suggested (V{sub 40} <65-70%). Previous abdominal/pelvic surgery correlated with all toxicity types; thus, a modified constraint for bleeding (V{sub 70} <15%) can be suggested for patients with a history of abdominal/pelvis surgery, although

  3. 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

  4. Prostate-specific antigen kinetics after primary stereotactic body radiation therapy using CyberKnife for localized prostate cancer

    PubMed Central

    Park, Yong Hyun; Choi, In Young; Yoon, Sei Chul; Jang, Hong Seok; Moon, Hyong Woo; Hong, Sung-Hoo; Kim, Sae Woong; Hwang, Tae-Kon; Lee, Ji Youl

    2015-01-01

    Purpose To assess prostate-specific antigen (PSA) kinetics and report on the oncologic outcomes for patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT) using CyberKnife. Methods We extracted the list and data of 39 patients with clinically localized prostate cancer who had undergone primary SBRT using CyberKnife between January 2008 and December 2012 from the Smart Prostate Cancer database system of Seoul St. Mary's Hospital. Changes in PSA over time, PSA velocity, and PSA nadir were evaluated from the completion of SBRT using CyberKnife. Biochemical recurrence (BCR)-free survival after primary SBRT using CyberKnife was determined using Kaplan–Meier analysis. Results The rate of PSA decrease was maximal in the first month (median −3.34 ng/mL/mo), which then fell gradually with median values of −1.51, −0.32, −0.28, −0.20, and −0.03 ng/mL/mo for durations of 3, 6, 9, 12, and 24 months after SBRT using CyberKnife, respectively. The median PSA nadir was 0.31 ng/mL after a median 23 months. Kaplan–Meier analysis calculates an actuarial 5-year BCR-free survival after SBRT using CyberKnife as 80.8%. Conclusions PSA decline occurred rapidly in the first month, and then the rate of PSA decline fell off steadily over time throughout 2 years after treatment. Also, SBRT using CyberKnife leads to long-term favorable BCR-free survival in localized prostate cancer. PMID:26157760

  5. Management of high-risk localized prostate cancer.

    PubMed

    Marciscano, Ariel E; Hardee, Matthew E; Sanfilippo, Nicholas

    2012-01-01

    Traditionally, patients with high-risk localized prostate cancer have been an extremely challenging group to manage due to a significant likelihood of treatment failure and prostate cancer-specific mortality (PCSM). The results of multiple large, prospective, randomized trials have demonstrated that men with high-risk features who are treated in a multimodal fashion at the time of initial diagnosis have improved overall survival. Advances in local treatments such as dose-escalated radiotherapy in conjunction with androgen suppression and postprostatectomy adjuvant radiotherapy have also demonstrated benefits to this subset of patients. However, therapeutic enhancement with the addition of chemotherapy to the primary treatment regimen may help achieve optimal disease control.

  6. 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

  7. Prostate cancer in dogs: comparative and clinical aspects.

    PubMed

    Leroy, Bruce E; Northrup, Nicole

    2009-05-01

    The canine prostate gland shares many morphological and functional similarities with the human prostate and dogs are the only other large mammals that commonly develop spontaneous prostate cancer. However, the incidence of prostate cancer is much lower in dogs and the precise cell of origin is not known. Dogs with prostate cancer usually present with advanced disease that does not respond to androgen deprivation therapy. Similar to humans, affected dogs often develop osteoblastic bone metastases in the pelvis and/or lumbar spine with associated pain and neurological deficits. Other clinical signs include weight loss, lethargy, and abnormal urination and/or defecation. Surgery, chemotherapy, and radiation have been used to treat dogs with prostate cancer, but success has been limited by the location and aggressive nature of the disease. It is evident that better methods of early detection and more effective therapies are needed for prostate cancer in dogs and advanced prostate carcinoma in men. Dogs with naturally-occurring prostate cancer are relevant models for the disease in humans and pre-clinical studies of new diagnostics and therapies in dogs may benefit both humans and dogs with prostate cancer.

  8. Salvage image-guided intensity modulated or stereotactic body reirradiation of local recurrence of prostate cancer

    PubMed Central

    Jereczek-Fossa, B A; Fodor, C; Bazzani, F; Maucieri, A; Ronchi, S; Ferrario, S; Colangione, S P; Gerardi, M A; Caputo, M; Cecconi, A; Gherardi, F; Vavassori, A; Comi, S; Cambria, R; Garibaldi, C; Cattani, F; De Cobelli, O; Orecchia, R

    2015-01-01

    Objective: To retrospectively evaluate external beam reirradiation (re-EBRT) delivered to the prostate/prostatic bed for local recurrence, after radical or adjuvant/salvage radiotherapy (RT). Methods: 32 patients received re-EBRT between February 2008 and October 2013. All patients had clinical/radiological local relapse in the prostate or prostatic bed and no distant metastasis. re-EBRT was delivered with selective RT technologies [stereotactic RT including CyberKnifeTM (Accuray, Sunnyvale, CA); image-guidance and intensity-modulated RT etc.]. Toxicity was evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Biochemical control was assessed according to the Phoenix definition (NADIR + 2 ng ml−1). Results: Acute urinary toxicity: G0, 24 patients; G1, 6 patients; G2, 2 patients. Acute rectal toxicity: G0, 28 patients; G1, 2 patients; and G2, 1 patient. Late urinary toxicity (evaluated in 30 cases): G0, 23 patients; G1, 6 patients; G2, 1 patient. Late renal toxicity: G0, 25 patients; G1, 5 patients. A mean follow-up of 21.3 months after re-EBRT showed that 13 patients were free of cancer, 3 were alive with biochemical relapse and 12 patients were alive with clinically evident disease. Four patients had died: two of disease progression and two of other causes. Conclusion: re-EBRT using modern technology is a feasible approach for local prostate cancer recurrence offering 2-year tumour control in about half of the patients. Toxicity of re-EBRT is low. Future studies are needed to identify the patients who would benefit most from this treatment. Advances in knowledge: Our series, based on experience in one hospital alone, shows that re-EBRT for local relapse of prostate cancer is feasible and offers a 2-year cure in about half of the patients. PMID:26055506

  9. Locally advanced prostate cancer: current controversies and optimisation opportunities.

    PubMed

    Sridharan, S; Dal Pra, A; Catton, C; Bristow, R G; Warde, P

    2013-08-01

    Prostate cancer is the most common malignancy in men worldwide. The rate of patients presenting with locally advanced prostate cancer has declined in recent decades, mainly due to prostate-specific antigen screening, but the management of these patients still remains controversial. Current literature suggests that the standard of care for these patients is a combination approach with radiation therapy and androgen deprivation therapy. However, there remain many unresolved issues, including the role of dose-escalated radiation therapy, the additional benefit of surgery and the role of systemic therapy, both standard chemotherapeutic agents and novel agents. Furthermore, in the era of personalised medicine, additional research is needed to evaluate the role of biomarkers to better predict the risk of local and systemic relapse in this population.

  10. 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.

  11. Nuclear vs Cytoplasmic localization of Filamin A in Prostate Cancer: Immunohistochemical Correlation with Metastases

    PubMed Central

    Bedolla, Roble G.; Wang, Yu; Asuncion, Alfredo; Chamie, Karim; Siddiqui, Salma; Mudryj, Maria M.; Prihoda, Thomas J.; Siddiqui, Javed; Chinnaiyan, Arul M.; Mehra, Rohit; deVereWhite, Ralph W.; Ghosh, Paramita M.

    2009-01-01

    Purpose We previously showed that nuclear localization of the actin-binding protein FilaminA (FlnA) corresponded to hormone-dependence in prostate cancer (Oncogene, 2007, 26:6061-6070). Intact FlnA (280kDa, cytoplasmic) cleaved to a 90kDa fragment which translocated to the nucleus in hormone-naïve cells, whereas in hormone-refractory cells, FlnA was phosphorylated, preventing its cleavage and nuclear translocation. We now examined whether FlnA localization determines a propensity to metastasis in advanced androgen independent prostate cancer. Experimental Design We examined, by immunohistochemistry, FlnA localization in paraffin-embedded human prostate tissue representing different stages of progression. Results were correlated with in vitro studies in a cell model of prostate cancer. Results Nuclear FlnA was significantly higher in benign prostate (0.6612±0.5888), PIN (0.6024±0.4620) and clinically localized cancers (0.69134±0.5686), compared to metastatic prostate cancers (0.3719±0.4992, p=0.0007). Cytoplasmic FlnA increased from benign prostate (0.0833±0.2677), PIN (0.1409±0.2293), localized cancers (0.3008±0.3762, p=0.0150), to metastases (0.7632±0.4414, p<0.00001). Logistic regression of metastatic vs non-metastatic tissue yielded the area-under-ROC curve as 0.67 for nuclear-FlnA, 0.79 for cytoplasmic-FlnA and 0.82 for both, indicating that metastasis correlates with cytoplasmic-to-nuclear translocation. In vitro studies showed that cytoplasmic localization of FlnA induced cell invasion whereas nuclear translocation of the protein inhibited it. FlnA dephosphorylation with the PKA inhibitor H-89 facilitated FlnA nuclear translocation, resulting in decreased invasiveness and AR transcriptional activity, and induced sensitivity to androgen withdrawal in hormone-refractory cells. Conclusions The data presented in this study indicate that in prostate cancer, metastasis correlates with cytoplasmic localization of FlnA and may be prevented by cleavage and

  12. Local Anesthesia During Interstitial Laser Coagulation of the Prostate

    PubMed Central

    Kedia, Kalish R

    2005-01-01

    With the emergence of minimally invasive therapies for the management of symptoms of benign prostatic hyperplasia (BPH), as well as the reality of a changing medical economic environment, there is a need for a reliable local anesthesia protocol. The protocol described here for prostate anesthetic block is a safe, economical, and effective way to perform interstitial laser coagulation and other minor endoscopic urologic procedures in the office setting. Most patients experience little discomfort and recover quickly, with prompt return to normal activities. Urologists should be aware of and comfortable with these techniques. PMID:16985900

  13. Optimal Management of Prostate Cancer Based on its Natural Clinical History.

    PubMed

    Facchini, Gaetano; Perri, Francesco; Misso, Gabriella; D Aniello, Carmine; Scarpati, Giuseppina Della Vittoria; Rossetti, Sabrina; Pepa, Chiara Della; Pisconti, Salvatore; Unteregger, Gerhard; Cossu, Alessia; Caraglia, Michele; Berretta, Massimiliano; Cavaliere, Carla

    2017-02-08

    Prostate cancer is the most common malignancy in males and, despite a marked improvement in diagnostic techniques, a not small percentage of prostate tumours is still diagnosed in advanced stage. It is now clear that prostate cancer passes through distinct phases during its natural history, starting from an initial phase, in which the disease has a locoregional extent, until a very late phase when it becomes refractory to hormone therapy. It is important to distinguish between local disease, in which tumor may be considered localized in the gland and a systemic disease characterized by high tumor burden and/or dissemination of circulating tumour cells. All the prostate cancers, at first diagnosis, are characterized by high sensitivity to the androgen deprivation therapy (ADT); however, during the natural history, after a variable period, they become castration resistant. In the past, few therapy options were available for castration resistant prostate cancer, while at present much more approaches can be employed, both hormone-based therapies and chemotherapy regimens. Hypercastration agents are defined as drugs capable to target the androgen-androgen receptor axis even in castrate resistant conditions. Abiraterone and enzalutamide are the only two hypercastration agents available for clinical use. Osteoclast targeted agents, such as zoledronic acid and denosumab can always been employed, but their use should be limited to the castrate resistant setting. The optimal understanding of all phases characterizing the natural history of prostate cancer may certainly be useful for the selection of the best therapeutic options in prostate cancer.

  14. Evolving treatment paradigms for locally advanced and metastatic prostate cancer.

    PubMed

    Dorff, Tanya B; Quek, Marcus L; Daneshmand, Siamak; Pinski, Jacek

    2006-11-01

    While men with early stage prostate cancer typically enjoy long-term survival after definitive management, for those who present with locally advanced or metastatic disease, survival is compromised. Multimodality therapy can prolong survival in these patients, with state-of-the-art options including intensity-modulated radiation or brachytherapy in conjunction with androgen ablation, adjuvant androgen ablation and/or chemotherapy with radical retropubic prostatectomy. In addition, novel biological therapies are being explored to target the unique molecular changes in prostate cancer cells and their interactions with the microenvironment. With these advances the outlook will undoubtedly improve, even for patients presenting with advanced disease. Careful application of these emerging therapies to a select group of prostate cancer patients most likely to obtain benefit from them is the challenge for urologists, medical oncologists and radiation oncologists for the future.

  15. 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

  16. Attitude of African-Americans regarding prostate cancer clinical trials.

    PubMed

    Robinson, S B; Ashley, M; Haynes, M A

    1996-04-01

    The purpose of this study was to qualitatively assess attitudes associated with the willingness of African-Americans to participate in prostate cancer clinical trials. Fifty-six African-American males, 40 years of age and older, were recruited from South Central Los Angeles. Respondents were divided into lower or middle socio-economic groups based on education and occupation. Focus group discussions were conducted to assess their knowledge about prostate cancer and willingness to participate in prostate cancer clinical trials. In addition, information was obtained to identify their incentives and barriers towards participating in prostate cancer research. Middle socio-economic respondents expressed a greater willingness to participate in prostate cancer clinical trials than did men of lower socio-economic status. Many indicated that they would be more likely to participate if they were encouraged to do so by a physician or researcher who was viewed as being competent and compassionate. Barriers to participation in prostate cancer clinical trials included concerns about drug toxicity, medical experimentation and distrust of the medical establishment. Endeavors aimed at increasing minority representation in prostate cancer clinical studies should address these issues.

  17. 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.

  18. 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.

  19. 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

  20. Oral selenium supplementation has no effect on prostate-specific antigen velocity in men undergoing active surveillance for localized prostate cancer.

    PubMed

    Stratton, M Suzanne; Algotar, Amit M; Ranger-Moore, James; Stratton, Steven P; Slate, Elizabeth H; Hsu, Chiu-Hsieh; Thompson, Patricia A; Clark, Larry C; Ahmann, Frederick R

    2010-08-01

    The Nutritional Prevention of Cancer trial showed a 52% lower incidence of prostate cancer in men supplemented with selenium. As a result, our study was designed to assess whether selenium supplementation attenuates the progression of prostate cancer. A phase 2 randomized, double-blind, placebo-controlled clinical trial was conducted in men with localized nonmetastatic prostate cancer who had elected to forgo active treatment and be followed by active surveillance. A total of 140 men were randomized to placebo (n = 46), 200 microg/d (n = 47), or 800 microg/d (n = 47) selenium p.o. (as selenized yeast) and followed every 3 months for up to 5 years. Prostate-specific antigen (PSA) velocity was used as a marker of prostate cancer progression and was estimated using mixed-effects regression. Adjusting for age, body mass index, baseline selenium, smoking, baseline PSA, race, PSA method, and Gleason score, PSA velocities for the 200 microg/d and 800 microg/d treatment groups were not statistically significantly different from placebo (P = 0.32 and P = 0.61, respectively). In the highest quartile of baseline selenium, men supplemented with 800 microg selenium showed statistically significantly higher PSA velocity as compared with placebo (P = 0.018). Selenium supplementation did not show a protective effect on PSA velocity in subjects with localized prostate cancer. On the contrary, supplementation with high-dose selenium was observed to be a risk factor for increased PSA velocity in men with high baseline plasma selenium concentrations.

  1. Neoadjuvant therapy for localized prostate cancer: Examining mechanism of action and efficacy within the tumor

    PubMed Central

    Lou, David Y.; Fong, Lawrence

    2015-01-01

    Objectives Efforts to improve the clinical outcome for patients with localized high-risk prostate cancer have led to the development of neoadjuvant systemic therapies. We review the different modalities of neoadjuvant therapies for localized prostate cancer and highlight emerging treatment approaches including immunotherapy and targeted therapy. Methods We performed a PubMed search of clinical trials evaluating preoperative systemic therapies for treating high-risk prostate cancer published after 2000, and those studies with the highest clinical relevance to current treatment approaches were selected for review. The database at clinicaltrials.gov was queried for neoadjuvant studies in high-risk prostate cancer, and those evaluating novel targeted therapies and immunotherapies are spotlighted here. Results Neoadjuvant chemotherapy has become standard of care for treating some malignancies, including breast and bladder cancers. In prostate cancer, preoperative hormonal therapy or chemotherapy has failed to demonstrate improvements in overall survival. Nevertheless, the emergence of novel treatment modalities such as targeted small molecules and immunotherapy has spawned neoadjuvant clinical trials that provide a unique vantage from which to study mechanism of action and biological potency. Tissue-based biomarkers are being developed to elucidate the biological efficacy of these treatments. With targeted therapy, these can include phospho-proteomic signatures of target pathway activation and deactivation. With immunotherapies, including sipuleucel-T and ipilimumab, recruitment of immune cells to the tumor microenvironment can also be used as robust markers of a biological effect. Such studies can provide insight not only into mechanism of action for these therapies but can also provide paths forward to improving clinical efficacy like with rationally designed combinations and dose selection. Conclusions The use of neoadjuvant androgen-deprivation therapy and

  2. Magnetic resonance imaging for prostate cancer clinical application

    PubMed Central

    Li, Bing; Du, Yong; Huang, Yayong; Meng, Jun; Xiao, Dongmei

    2013-01-01

    As prostate cancer is a biologically heterogeneous disease for which a variety of treatment options are available, the major objective of prostate cancer imaging is to achieve more precise disease characterization. In clinical practice, magnetic resonance imaging (MRI) is one of the imaging tools for the evaluation of prostate cancer, the fusion of MRI or dynamic contrast-enhanced MRI (DCE-MRI) with magnetic resonance spectroscopic imaging (MRSI) is improving the evaluation of cancer location, size, and extent, while providing an indication of tumor aggressiveness. This review summarizes the role of MRI in the application of prostate cancer and describes molecular MRI techniques (including MRSI and DCE-MRI) for aiding prostate cancer management. PMID:23592906

  3. Management of High-Risk Localized Prostate Cancer

    PubMed Central

    Marciscano, Ariel E.; Hardee, Matthew E.; Sanfilippo, Nicholas

    2012-01-01

    Traditionally, patients with high-risk localized prostate cancer have been an extremely challenging group to manage due to a significant likelihood of treatment failure and prostate cancer-specific mortality (PCSM). The results of multiple large, prospective, randomized trials have demonstrated that men with high-risk features who are treated in a multimodal fashion at the time of initial diagnosis have improved overall survival. Advances in local treatments such as dose-escalated radiotherapy in conjunction with androgen suppression and postprostatectomy adjuvant radiotherapy have also demonstrated benefits to this subset of patients. However, therapeutic enhancement with the addition of chemotherapy to the primary treatment regimen may help achieve optimal disease control. PMID:22110494

  4. Computerised triage in a prostate assessment clinic.

    PubMed

    Rajkumar, G N; Small, D R; Conn, I G

    2004-01-01

    An MS Office package has been developed to score IPSS, take a patient history, compare flows with nomograms and decide on interim management. This is based on these scores, residual volume and laboratory results. A clearly formatted GP letter is produced. The patient uses a touch screen to answer questions on the IPSS and other medical history. These questions and responses are stored in Excel spread sheets. Clinic staff then enter results of flow studies, urinalysis, U&E and PSA. Excel Visual Basic creates a detailed printout for the notes and the MS Office mail merge facility creates a summary printout, which also serves as a letter to the GP. Excel allows embedding of formulae and program code to implement the rules for management. Based on these rules, the program either generates a request for an urgent appointment in the clinic or recommends the use of either an alpha blocker (if not contraindicated by medical history) or 5 alpha reductase inhibitors in the interim period before they are reviewed in clinic. A total of 139 patients have been seen and the computer decisions compared with those of a consultant urologist. Agreement was found in 106, disagreement in 33. However, 21 of the 33 involved computer oversensitivity to flow results. We do not anticipate difficulty improving this and are investigating using an artificial neural network. Of the other 12 patients, the urologist departed from the fixed rules for IPSS, creatinine, PSA and residual urine when only one variable was slightly abnormal. To conclude, this novel user-friendly system shows great potential in the management of prostate outpatients. Some tuning is needed, with particular respect to uroflow results.

  5. Cytoprotective Mitochondrial Chaperone TRAP-1 As a Novel Molecular Target in Localized and Metastatic Prostate Cancer

    PubMed Central

    Leav, Irwin; Plescia, Janet; Goel, Hira Lal; Li, Jing; Jiang, Zhong; Cohen, Ronald J.; Languino, Lucia R.; Altieri, Dario C.

    2010-01-01

    Molecular chaperones of the heat shock protein-90 (Hsp90) family promote cell survival, but the molecular requirements of this pathway in tumor progression are not understood. Here, we show that a mitochondria-localized Hsp90 chaperone, tumor necrosis factor receptor-associated protein-1 (TRAP-1), is abundantly and ubiquitously expressed in human high-grade prostatic intraepithelial neoplasia, Gleason grades 3 through 5 prostatic adenocarcinomas, and metastatic prostate cancer, but largely undetectable in normal prostate or benign prostatic hyperplasia in vivo. Prostate lesions formed in genetic models of the disease, including the transgenic adenocarcinoma of the mouse prostate and mice carrying prostate-specific deletion of the phosphatase tensin homolog tumor suppressor (Ptenpc−/−), also exhibit high levels of TRAP-1. Expression of TRAP-1 in nontransformed prostatic epithelial BPH-1 cells inhibited cell death, whereas silencing of TRAP-1 in androgen-independent PC3 or DU145 prostate cancer cells by small interfering RNA enhanced apoptosis. Targeting TRAP-1 with a novel class of mitochondria-directed Hsp90 inhibitors, ie, Gamitrinibs, caused rapid and complete killing of androgen-dependent or -independent prostate cancer, but not BPH-1 cells, whereas reintroduction of TRAP-1 in BPH-1 cells conferred sensitivity to Gamitrinib-induced cell death. These data identify TRAP-1 as a novel mitochondrial survival factor differentially expressed in localized and metastatic prostate cancer compared with normal prostate. Targeting this pathway with Gamitrinibs could be explored as novel molecular therapy in patients with advanced prostate cancer. PMID:19948822

  6. Solitary recurrence of castration-resistant prostate cancer with low or undetectable levels of prostate specific antigen salvaged with local ablative radiation therapy: A case report

    PubMed Central

    WANG, CHIACHIEN JAKE; YING, JAMES; KAPUR, PAYAL; WOHLFELD, BRYAN; ROEHRBORN, CLAUS; KIM, DONG W. NATHAN

    2016-01-01

    Prostate cancer recurrences are usually first detected by increased levels of prostate specific antigen (PSA), and systemic therapy is often initiated if distant metastasis is confirmed. However, low or nearly undetectable levels of PSA in the modern era of ultrasensitive PSA assay may be difficult to interpret in patients with a history of prostate cancer. Deciding whether to initiate additional systemic therapy in limited indolent metastatic disease while balancing the quality of life of the patient and ensuring the oncologic control of the disease may be challenging. In the present study, the case of a biopsy-confirmed solitary spine recurrence of prostate cancer with nearly undetectable but persistent levels of PSA (0.05 ng/ml) is reported. Treatment of the recurrence with local ablative radiotherapy improved the pain experienced by the patient, and reduced his levels of PSA to undetectable limits (<0.05 ng/ml). Repeated imaging analysis, PSA assay and clinical assessment demonstrated durable control of the disease without the requirement for additional systemic treatments. The present case highlighted the importance of initiating appropriate work-up according to the clinical scenario. Local treatment for solitary or oligometastatic recurrence of prostate cancer may enhance the effectiveness of current therapeutic strategies and benefit certain patients. PMID:26870272

  7. Pre-clinical Orthotopic Murine Model of Human Prostate Cancer.

    PubMed

    Shahryari, Varahram; Nip, Hannah; Saini, Sharanjot; Dar, Altaf A; Yamamura, Soichiro; Mitsui, Yozo; Colden, Melissa; Bucay, Nathan; Tabatabai, Laura Z; Greene, Kirsten; Deng, Guoren; Tanaka, Yuichiro; Dahiya, Rajvir; Majid, Shahana

    2016-08-29

    To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information about this disease. The human orthotopic prostate cancer xenograft mouse model provides a useful alternative approach for understanding the specific interactions between genetically and molecularly altered tumor cells, their organ microenvironment, and for evaluation of efficacy of therapeutic regimens. This is a well characterized model designed to study the molecular events of primary tumor development and it recapitulates the early events in the metastatic cascade prior to embolism and entry of tumor cells into the circulation. Thus it allows elucidation of molecular mechanisms underlying the initial phase of metastatic disease. In addition, this model can annotate drug targets of clinical relevance and is a valuable tool to study prostate cancer progression. In this manuscript we describe a detailed procedure to establish a human orthotopic prostate cancer xenograft mouse model.

  8. Controversies in the management of localized prostate cancer: radical prostatectomy still the standard of care.

    PubMed

    Budäus, Lars; Huland, Hartwig; Graefen, Markus

    2012-12-01

    The optimal treatment for clinically localized prostate cancer is an ongoing subject of controversy. Treatment decisions must take tumour staging, risk assessment, life expectancy and consideration of the major side effects of multiple available treatment regimens into account. Despite technical advances reduced the side effects of radiation therapy, the majority of patients with newly diagnosed organ confined prostate cancer decide to undergo radical prostatectomy. Refinements of radical prostatectomy surgical techniques during the last decade are influenced by better understanding of the anatomy of the small pelvis and resulted in excellent functional and oncological outcomes. Additionally, the surgeons experience was identified as a key determinant for improved surgical outcomes. Recently, retrospective studies revealed that also patients with locally advanced disease benefit from radical prostatectomy. Advantages of radical prostatectomy include a precise pathological staging that assesses the need for additional therapies. Moreover, PSA can easily be used as an accurate surrogate marker during follow-up in such patients.

  9. Prostate Cancer Clinical Trials Group: The University of Michigan Site

    DTIC Science & Technology

    2012-04-01

    and fusion-negative strata. UM will be the lead site for this trial with the Univ. of Chicago N01 Phase II consortium as the coordinating center. Ten...sensitive prostate cancer: a University of Chicago Phase II Consortium/Department of Defense Prostate Cancer Clinical Trials Consortium study. JE Ward, T...N01 contract with CTEP (University of Chicago – Early Therapeutics Development with Phase II emphasis group). The Program is committed to creating

  10. Increasing Sustained Participation in Free Mass Prostate Cancer Screening Clinics

    DTIC Science & Technology

    2006-05-01

    of prostate cancer screening promotion once the church leaders identify men’s health as a priority. The study sample contained 1,882 individuals...content, and herbals such as vitamin E, Selenium, and Lycopene . Overall, the physicians felt that prostate cancer is such a multi-factorial disease...screening clinics. To increase the pool of lower-income African American men in the longitudinal database for study cohort, over sampling was done by

  11. Real-time photoacoustic imaging of prostate brachytherapy seeds using a clinical ultrasound system

    NASA Astrophysics Data System (ADS)

    Kuo, Nathanael; Kang, Hyun Jae; Song, Danny Y.; Kang, Jin U.; Boctor, Emad M.

    2012-06-01

    Prostate brachytherapy is a popular prostate cancer treatment option that involves the permanent implantation of radioactive seeds into the prostate. However, contemporary brachytherapy procedure is limited by the lack of an imaging system that can provide real-time seed-position feedback. While many other imaging systems have been proposed, photoacoustic imaging has emerged as a potential ideal modality to address this need, since it could easily be incorporated into the current ultrasound system used in the operating room. We present such a photoacoustic imaging system built around a clinical ultrasound system to achieve the task of visualizing and localizing seeds. We performed several experiments to analyze the effects of various parameters on the appearance of brachytherapy seeds in photoacoustic images. We also imaged multiple seeds in an ex vivo dog prostate phantom to demonstrate the possibility of using this system in a clinical setting. Although still in its infancy, these initial results of a photoacoustic imaging system for the application of prostate brachytherapy seed localization are highly promising.

  12. Cancer Localization in the Prostate with F-18 Fluorocholine Position Emission Tomography

    DTIC Science & Technology

    2008-01-01

    prostate cancer sextant localization on the basis of measured fluorocholine uptake. The data acquired thus far with conventional PET in 15 subjects...emission tomography (PET) detection of malignancy in anatomical sextants of the prostate gland. The rationale for evaluating fluorocholine as an...correlation with step-section prostate histopathology to assess the accuracy of sextant detection of prostate malignancy based on this technique. With

  13. 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

  14. 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.

  15. Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for Older Men With Locally Advanced Prostate Cancer

    PubMed Central

    Bekelman, Justin E.; Mitra, Nandita; Handorf, Elizabeth A.; Uzzo, Robert G.; Hahn, Stephen A.; Polsky, Daniel; Armstrong, Katrina

    2015-01-01

    Purpose We examined whether the survival advantage of androgen-deprivation therapy with radiotherapy (ADT plus RT) relative to ADT alone for men with locally advanced prostate cancer reported in two randomized trials holds in real-world clinical practice and extended the evidence to patients poorly represented in the trials. Methods We conducted nonrandomized effectiveness studies of ADT plus RT versus ADT in three groups of patients diagnosed between 1995 and 2007 and observed through 2009 in the SEER-Medicare data set: (1) the randomized clinical trial (RCT) cohort, which included men age 65 to 75 years and was most consistent with participants in the randomized trials; (2) the elderly cohort, which included men age > 75 years with locally advanced prostate cancer; and (3) the screen-detected cohort, which included men age ≥ 65 years with screen-detected high-risk prostate cancer. We evaluated cause-specific and all-cause mortality using propensity score, instrumental variable (IV), and sensitivity analyses. Results In the RCT cohort, ADT plus RT was associated with reduced cause-specific and all-cause mortality relative to ADT alone (cause-specific propensity score–adjusted hazard ratio [HR], 0.43; 95% CI, 0.37 to 0.49; all-cause propensity score–adjusted HR, 0.63; 95% CI, 0.59 to 0.67). Effectiveness estimates for the RCT cohort were not significantly different from those from randomized trials (P > .1). In the elderly and screen-detected cohorts, ADT plus RT was also associated with reduced cause-specific and all-cause mortality. IV analyses produced estimates similar to those from propensity score–adjusted methods. Conclusion Older men with locally advanced or screen-detected high-risk prostate cancer who receive ADT alone risk decrements in cause-specific and overall survival. PMID:25559808

  16. Toxicity outcome in patients treated with modulated arc radiotherapy for localized prostate cancer

    PubMed Central

    Lengua, Rafael E.; Gonzalez, Maria F.; Barahona, Kaory; Ixquiac, Milton E.; Lucero, Juan F.; Montenegro, Erick; Lopez Guerra, Jose L.; Jaén, Javier; Linares, Luis A.

    2013-01-01

    Aim This study evaluates the acute toxicity outcome in patients treated with RapidArc for localized prostate cancer. Background Modern technologies allow the delivery of high doses to the prostate while lowering the dose to the neighbouring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known. Materials and methods Between December 2009 and May 2012, 45 patients with primary prostate adenocarcinoma were treated using RapidArc. All patients received 1.8 Gy per fraction, the median dose to the prostate gland, seminal vesicles, pelvic lymph nodes and surgical bed was 80 Gy (range, 77.4–81 Gy), 50.4 Gy, 50.4 Gy and 77.4 Gy (range, 75.6–79.2 Gy), respectively. Results The time between the last session and the last treatment follow up was a median of 10 months (range, 3–24 months). The incidence of grade 3 acute gastrointestinal (GI) and genitourinary (GU) toxicity was 2.2% and 15.5%, respectively. Grade 2 acute GI and GU toxicity occurred in 30% and 27% of patients, respectively. No grade 4 acute GI and GU toxicity were observed. Older patients (>median) or patients with V60 higher than 35% had significantly higher rates of grade ≥2 acute GI toxicity compared with the younger ones. Conclusions RapidArc in the treatment of localized prostate cancer is tolerated well with no Grade >3 GI and GU toxicities. Older patients or patients with higher V60 had significantly higher rates of grade ≥2 acute GI toxicity. Further research is necessary to assess definitive late toxicity and tumour control outcome. PMID:25061516

  17. Immunohistochemical analysis of estrogen receptors in prostate and clinical correlation in men with benign prostatic hyperplasia

    PubMed Central

    Gangkak, Goto; Mittal, Alka; Yadav, Sher Singh; Tomar, Vinay; Yadav, Ajay; Mehta, Jayanti

    2017-01-01

    Purpose Estrogens act through interaction with 2 receptor subtypes, ER alpha (ERα) and ER beta (ERβ), in human prostate. The aim of the present study was to semiquantitatively assess the differential expression of ER subtypes in human benign prostatic hyperplasia (BPH) by use of immunocytochemistry (IHC) methods and to explore their relationship with various measures of BPH. Materials and Methods A total of 45 patients with BPH undergoing transurethral resection of the prostate and 22 patients with bladder cancer with normal prostate undergoing surveillance cystoscopy were studied as cases and controls, respectively. Quantitative immunolabeling of ER subtypes was scored by use of a semiquantitative scale. Also, correlations were assessed between ER levels in prostate and various measures of BPH. Results Overall, we found strong immunostaining for ERα in stroma and for ERβ in epithelium, respectively. The IHC score for ERα differed significantly between BPH patients and controls in both stroma (p≤0.001) and epithelium (p=0.008), respectively. The ERβ IHC score was also significantly higher in the epithelium of BPH patients (p=0.01). Also, we found a significant correlation between prostatic ER levels and various clinical measures of BPH. Conclusions ERs may play an important role in the pathogenesis of BPH. PMID:28261681

  18. Multi-Institutional Registry for Prostate Cancer Radiosurgery: A Prospective Observational Clinical Trial

    PubMed Central

    Freeman, Debra; Dickerson, Gregg; Perman, Mark

    2015-01-01

    Objective: To report on the design, methodology, and early outcome results of a multi-institutional registry study of prostate cancer radiosurgery. Methods: The Registry for Prostate Cancer Radiosurgery (RPCR) was established in 2010 to further evaluate the efficacy and toxicity of prostate radiosurgery (SBRT) for the treatment of clinically localized prostate cancer. Men with prostate cancer were asked to voluntarily participate in the registry. Demographic, baseline medical, and treatment-related data were collected and stored electronically in a Health Insurance Portability and Accountability Act-compliant database, maintained by Advertek, Inc. Enrolled men were asked to complete short, multiple choice questionnaires regarding their bowel, bladder, and sexual function. Patient-reported outcome forms were collected at baseline and at regular intervals (every 3–6 months) following treatment. Serial prostate-specific antigen measurements were obtained at each visit and included in the collected data. Results: From July 2010 to July 2013, nearly 2000 men from 45 participating sites were enrolled in the registry. The majority (86%) received radiosurgery as monotherapy. At 2 years follow-up, biochemical disease-free survival was 92%. No Grade 3 late urinary toxicity was reported. One patient developed Grade 3 gastrointestinal toxicity (rectal bleeding). Erectile function was preserved in 80% of men <70 years old. Overall compliance with data entry was 64%. Conclusion: Stereotactic radiosurgery is an alternative option to conventional radiotherapy for the treatment of organ-confined prostate cancer. The RPCR represents the collective experience of multiple institutions, including community-based cancer centers, with outcome results in keeping with published, prospective trials of prostate SBRT. PMID:25657929

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

    PubMed

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

    2017-04-01

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

  20. Cancer Localization in the Prostate with F-18 Fluorocholine Positron Emission Tomography

    DTIC Science & Technology

    2009-01-15

    cancer sextant localization based on measured fluorocholine uptake. Recruitment of human subjects for this project was completed in 2008. A final one... sextants of the prostate gland. The rationale for evaluating fluorocholine as an oncologic tracer applicable to prostate cancer is based on observations...method of sextant localization of primary prostate cancer through a collaboration with Phillips Research (Phillips Medical Systems, N.A.). A proposal

  1. Cancer Localization in the Prostate with F-18 Fluorocholine Positron Emission Tomography. Addendum

    DTIC Science & Technology

    2010-01-01

    accuracy of prostate cancer sextant localization based on measured fluorocholine uptake. Recruitment of human subjects for this project was completed...of malignancy in anatomical sextants of the prostate gland. The rationale for evaluating fluorocholine as an oncologic tracer applicable to...potential means to further improve the sextant localization of primary prostate cancer. The rationale for this study is based on observations of rapid

  2. Target localization and toxicity in dose-escalated prostate radiotherapy with image-guided approach using daily planar kilovoltage imaging.

    PubMed

    Nath, S K; Sandhu, A P; Sethi, R A; Jensen, L G; Rosario, M D; Kane, C J; Parsons, J K; Millard, F E; Jiang, S B; Rice, R K; Pawlicki, T; Mundt, A J

    2011-02-01

    Dose escalation with intensity-modulated radiation therapy (IMRT) for carcinoma of the prostate has augmented the need for accurate prostate localization prior to dose delivery. Daily planar kilovoltage (kV) imaging is a low-dose image-guidance technique that is prevalent among radiation oncologists. However, clinical outcomes evaluating the benefit of daily kV imaging are lacking. The purpose of this study was to report our clinical experience, including prostate motion and gastrointestinal (GI) and genitourinary (GU) toxicities, using this modality. A retrospective analysis of 100 patients treated consecutively between December 2005 and March 2008 with definitive external beam IMRT for T1c-T4 disease were included in this analysis. Prescription doses ranged from 74-78 Gy (median, 76) in 2 Gy fractions and were delivered following daily prostate localization using on-board kV imaging (OBI) to localize gold seed fiducial markers within the prostate. Acute and late toxicities were graded as per the NCI CTCAEv3.0. The median follow-up was 22 months. The magnitude and direction of prostate displacement and daily shifts in three axes are reported. Of note, 9.1% and 12.9% of prostate displacements were ≥ 5 mm in the anterior-posterior and superior-inferior directions, respectively. Acute grade 2 GI and GU events occurred in 11% and 39% of patients, respectively, however no grade 3 or higher acute GI or GU events were observed. Regarding late toxicity, 2% and 17% of patients developed grade 2 toxicities, and similarly no grade 3 or higher events had occurred by last follow-up. Thus, kV imaging detected a substantial amount of inter-fractional displacement and may help reduce toxicity profiles, especially high grade events, by improving the accuracy of dose delivery.

  3. [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.

  4. A feature-based learning framework for accurate prostate localization in CT images.

    PubMed

    Liao, Shu; Shen, Dinggang

    2012-08-01

    Automatic segmentation of prostate in CT images plays an important role in medical image analysis and image guided radiation therapy. It remains as a challenging problem mainly due to three issues: First, the image contrast between the prostate and its surrounding tissues is low in prostate CT images and no obvious boundaries can be observed. Second, the unpredictable prostate motion causes large position variations of the prostate in the treatment images scanned at different treatment days. Third, the uncertainty of the existence of bowel gas in treatment images significantly changes the image appearance even for images taken from the same patient. To address these issues, in this paper we are motivated to propose a feature based learning framework for accurate prostate localization in CT images. The main contributions of the proposed method lie in the following aspects: (1) Anatomical features are extracted from input images and adopted as signatures for each voxel. The most robust and informative features are identified by the feature selection process to help localize the prostate. (2) Regions with salient features but irrelevant to the localization of prostate, such as regions filled with bowel gas are automatically filtered out by the proposed method. (3) An online update mechanism is adopted in this paper to adaptively combine both population information and patient-specific information to localize the prostate. The proposed method is evaluated on a CT prostate dataset of 24 patients to localize the prostate, where each patient has more than 10 longitudinal images scanned at different treatment times. It is also compared with several state-of- the-art prostate localization algorithms in CT images, and the experimental results demonstrate that the proposed method achieves the highest localization accuracy among all the methods under comparison.

  5. Obesity, age, ethnicity, and clinical features of prostate cancer patients

    PubMed Central

    Wu, Victor J; Pang, Darren; Tang, Wendell W; Zhang, Xin; Li, Li; You, Zongbing

    2017-01-01

    Approximately 36.5% of the U.S. adults (≥ 20 years old) are obese. Obesity has been associated with type 2 diabetes mellitus, cardiovascular disease, stroke, and several types of cancer. The present study included 1788 prostate cancer patients who were treated with radical prostatectomy at the Ochsner Health System, New Orleans, Louisiana, from January, 2001 to March, 2016. The patient’s medical records were retrospectively reviewed. Body mass index (BMI), age, ethnicity (Caucasians versus African Americans), clinical stage, Gleason score, and prostate-specific antigen (PSA) levels were retrieved. The relative risk of the patients was stratified into low risk and high risk groups. Associative analyses found that BMI was associated with age, clinical stage, Gleason score, but not ethnicity, PSA levels, or the relative risk in this cohort. Age was associated with ethnicity, clinical stage, Gleason score, and PSA levels, as well as the relative risk. Ethnicity was associated with Gleason score and PSA levels as well as the relative risk, but not clinical stage. These findings suggest that obesity is associated with advanced prostate cancer with stage T3 or Gleason score ≥ 7 diseases, and age and ethnicity are important factors that are associated with the clinical features of prostate cancer patients. PMID:28337464

  6. Randomized Trial of a Hypofractionated Radiation Regimen for the Treatment of Localized Prostate Cancer.

    PubMed

    Catton, Charles N; Lukka, Himu; Gu, Chu-Shu; Martin, Jarad M; Supiot, Stéphane; Chung, Peter W M; Bauman, Glenn S; Bahary, Jean-Paul; Ahmed, Shahida; Cheung, Patrick; Tai, Keen Hun; Wu, Jackson S; Parliament, Matthew B; Tsakiridis, Theodoros; Corbett, Tom B; Tang, Colin; Dayes, Ian S; Warde, Padraig; Craig, Tim K; Julian, Jim A; Levine, Mark N

    2017-03-15

    Purpose Men with localized prostate cancer often are treated with external radiotherapy (RT) over 8 to 9 weeks. Hypofractionated RT is given over a shorter time with larger doses per treatment than standard RT. We hypothesized that hypofractionation versus conventional fractionation is similar in efficacy without increased toxicity. Patients and Methods We conducted a multicenter randomized noninferiority trial in intermediate-risk prostate cancer (T1 to 2a, Gleason score ≤ 6, and prostate-specific antigen [PSA] 10.1 to 20 ng/mL; T2b to 2c, Gleason ≤ 6, and PSA ≤ 20 ng/mL; or T1 to 2, Gleason = 7, and PSA ≤ 20 ng/mL). Patients were allocated to conventional RT of 78 Gy in 39 fractions over 8 weeks or to hypofractionated RT of 60 Gy in 20 fractions over 4 weeks. Androgen deprivation was not permitted with therapy. The primary outcome was biochemical-clinical failure (BCF) defined by any of the following: PSA failure (nadir + 2), hormonal intervention, clinical local or distant failure, or death as a result of prostate cancer. The noninferiority margin was 7.5% (hazard ratio, < 1.32). Results Median follow-up was 6.0 years. One hundred nine of 608 patients in the hypofractionated arm versus 117 of 598 in the standard arm experienced BCF. Most of the events were PSA failures. The 5-year BCF disease-free survival was 85% in both arms (hazard ratio [short v standard], 0.96; 90% CI, 0.77 to 1.2). Ten deaths as a result of prostate cancer occurred in the short arm and 12 in the standard arm. No significant differences were detected between arms for grade ≥ 3 late genitourinary and GI toxicity. Conclusion The hypofractionated RT regimen used in this trial was not inferior to conventional RT and was not associated with increased late toxicity. Hypofractionated RT is more convenient for patients and should be considered for intermediate-risk prostate cancer.

  7. 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.

  8. 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.

  9. Clinical Factors Asssociated with Treatment Outcomes following Whole-brain Irradiation in Patients with Prostate Cancer

    PubMed Central

    DZIGGEL, LIESA; E. SCHILD, STEVEN; VENINGA, THEO; BAJROVIC, AMIRA; RADES, DIRK

    2017-01-01

    Background/Aim: Patients with prostate cancer represent a small minority of cancer patients presenting with metastases to the brain. This study investigated the role of whole-brain irradiation (WBI) in this rare group. Patients and Methods: Eighteen such patients were included. Clinical factors including fractionation program of WBI, age at WBI, Karnofsky performance score (KPS), number of metastases to the brain, involvement of extracerebral metastatic sites, time from prostate cancer diagnosis to WBI and recursive-partitioning-analysis (RPA) class were investigated regarding local (intracerebral) control and survival. Results: On multivariate evaluation, longer time from prostate cancer diagnosis to WBI showed a trend towards improved local control (hazard ratio 2.77, p=0.098). Better KPS (hazard ratio 5.64, p=0.021) and longer time from prostate cancer diagnosis to WBI (hazard ratio 5.64, p=0.013) were significantly associated with better survival. Conclusion: Two independent predictors of survival were identified and should be considered when designing for personalized treatment regimens and clinical trials. PMID:28064217

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. A systematic literature review of life expectancy prediction tools for localized prostate cancer patients

    PubMed Central

    Kent, Matthew; Vickers, Andrew J.

    2015-01-01

    Purpose We aimed to develop a clinical decision support tool for clinicians counseling patients with localized prostate cancer. The tool would provide estimates of patient life expectancy from age, comorbidities, and tumor characteristics. We reviewed the literature to find suitable prediction models. Materials and Methods We searched the literature for prediction models for life expectancy. Models were evaluated in terms of whether they provided an estimate of risk, incorporated comorbidities, were clinically feasible and gave plausible estimates. Clinical feasibility was defined in terms of whether the model provided coefficients, could be used in the initial consultation for men across a wide range of ages without an undue burden of data gathering. Results Models in the literature were characterized by the use of life years rather than a risk of death, questionable approaches to comorbidities, implausible estimates, questionable recommendations, and poor clinical feasibility. We found tools based on applying an unvalidated approach to assessing comorbidities to a clearly erroneous life expectancy table, or required a treatment decision be made before life expectancy could be calculated or gave highly implausible estimates, such as a substantial risk of prostate cancer specific mortality even for a highly comorbid 80 year old with Gleason 6 disease. Conclusions We found gross deficiencies in current tools that predict risk of death from other causes. No existing model was suitable for implementation in our clinical decision support system. PMID:25463998

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

    PubMed

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

    2012-10-07

    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.

  16. Acute urinary morbidity after a permanent 125I implantation for localized prostate cancer.

    PubMed

    Ohga, Saiji; Nakamura, Katsumasa; Shioyama, Yoshiyuki; Tatsugami, Katsunori; Sasaki, Tomonari; Nonoshita, Takeshi; Yoshitake, Tadamasa; Asai, Kaori; Hirata, Hideki; Naito, Seiji; Honda, Hiroshi

    2014-11-01

    We evaluated the predictive factors of acute urinary morbidity (AUM) after prostate brachytherapy. From November 2005 to January 2007, 62 patients with localized prostate cancer were treated using brachytherapy. The (125)Iodine ((125)I) seed-delivering method was a modified peripheral pattern. The prescribed dose was 144 Gy. Urinary morbidity was scored at 3 months after implantation. The clinical and treatment parameters were analysed for correlation with AUM. In particular, in this study, Du90 (the minimal dose received by 90% of the urethra), Dup90 (the minimal dose received by 90% of the proximal half of the urethra on the bladder side) and Dud90 (the minimal dose received by 90% of the distal half of the urethra on the penile side) were analysed. We found that 43 patients (69.4%) experienced acute urinary symptoms at 3 months after implantation. Of them, 40 patients had Grade 1 AUM, one patient had Grade 2 pain, and two patients had Grade 2 urinary frequency. None of the patients had ≥Grade 3. Univariate and multivariate analysis revealed that Du90 and Dup90 were significantly correlated with AUM. In this study, Du90 and Dup90 were the most significant predictors of AUM after prostate brachytherapy.

  17. 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.

  18. Newer Imaging Modalities to Assist With Target Localization in the Radiation Treatment of Prostate Cancer and Possible Lymph Node Metastases

    SciTech Connect

    John, Subhash S. Zietman, Anthony L.; Shipley, William U.; Harisinghani, Mukesh G.

    2008-05-01

    Precise localization of prostate cancer and the drainage lymph nodes is mandatory to define an accurate clinical target volume for conformal radiotherapy. Better target definition and delineation on a daily basis is surely important in quality assurance for fractionated radiation therapy. This article reviews the evidence for major emerging techniques that show promise in better identifying the clinical target volume. Partial prostate boost by brachytherapy, intensity-modulated radiation therapy, or protons has become possible not only with standard imaging techniques but also with the availability of metabolic images obtained by magnetic resonance spectroscopy. Even though fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography has not been found to be useful, novel radiolabeled tracers may eventually prove of value in the diagnosis and treatment planning of prostate cancer. For the metastatic lymph nodes, lymphotropic nanoparticle-enhanced magnetic resonance imaging using ultra-small superparamagnetic iron oxide particles has greater accuracy as compared with conventional techniques and has been instrumental in delineating the lymphatic drainage of the prostate gland. These novel investigational techniques could further help in optimizing conformal radiotherapy for patients with prostate cancer. The concepts of biologic target volume, real target volume, and multidimensional conformal radiotherapy are being explored.

  19. Newer imaging modalities to assist with target localization in the radiation treatment of prostate cancer and possible lymph node metastases.

    PubMed

    John, Subhash S; Zietman, Anthony L; Shipley, William U; Harisinghani, Mukesh G

    2008-01-01

    Precise localization of prostate cancer and the drainage lymph nodes is mandatory to define an accurate clinical target volume for conformal radiotherapy. Better target definition and delineation on a daily basis is surely important in quality assurance for fractionated radiation therapy. This article reviews the evidence for major emerging techniques that show promise in better identifying the clinical target volume. Partial prostate boost by brachytherapy, intensity-modulated radiation therapy, or protons has become possible not only with standard imaging techniques but also with the availability of metabolic images obtained by magnetic resonance spectroscopy. Even though fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography has not been found to be useful, novel radiolabeled tracers may eventually prove of value in the diagnosis and treatment planning of prostate cancer. For the metastatic lymph nodes, lymphotropic nanoparticle-enhanced magnetic resonance imaging using ultra-small superparamagnetic iron oxide particles has greater accuracy as compared with conventional techniques and has been instrumental in delineating the lymphatic drainage of the prostate gland. These novel investigational techniques could further help in optimizing conformal radiotherapy for patients with prostate cancer. The concepts of biologic target volume, real target volume, and multidimensional conformal radiotherapy are being explored.

  20. 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.

  1. 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

  2. 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.

  3. Why we should not routinely apply irreversible electroporation as an alternative curative treatment modality for localized prostate cancer at this stage.

    PubMed

    Wendler, J J; Ganzer, R; Hadaschik, B; Blana, A; Henkel, T; Köhrmann, K U; Machtens, S; Roosen, A; Salomon, G; Sentker, L; Witzsch, U; Schlemmer, H P; Baumunk, D; Köllermann, J; Schostak, M; Liehr, U B

    2017-01-01

    Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy of prostate cancer with its postulated features, especially the absence of a thermal ablation effect. Thus far, there is not enough evidence of its effectiveness or adverse effects to justify its use as a definitive treatment option for localized prostate cancer. Moreover, neither optimal nor individual treatment parameters nor uniform endpoints have been defined thus far. No advantages over established treatment procedures have as yet been demonstrated. Nevertheless, IRE is now being increasingly applied for primary prostate cancer therapy outside clinical trials, not least through active advertising in the lay press. This review reflects the previous relevant literature on IRE of the prostate or prostate cancer and shows why we should not adopt IRE as a routine treatment modality at this stage.

  4. 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

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

    PubMed

    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.

  6. Outcomes and predictors of localized or locally-advanced prostate cancer treated by radiotherapy in Indonesia

    PubMed Central

    Supit, Wempy; Mochtar, Chaidir Arif; Santoso, Rachmat Budi; Umbas, Rainy

    2013-01-01

    Purpose: Presently there is no published data on the outcomes of localized or locally-advanced prostate cancer (PCa) treated by external-beam radiotherapy (RT) in Indonesia. Methods: This study retrospectively analyzed 96 patients with localized or locally-advanced PCa treated by RT from year 1995 to 2009, at the national referral hospital and the national cancer hospital of Indonesia. Cumulative prostate and pelvic radiation dose/type was <70 Gy conventional RT in 84.4% patients, and ≥70 Gy Three dimensional-conformal or intensity modulated RT in 15.6% patients. Overall survival (OS) and biochemical progression-free survival (BFS) were estimated by Kaplan-Meier. Predictors of OS and biochemical recurrence were analyzed by multivariate Cox regressions. Results: The median follow-up was 61 months (range, 24 to 169 months). There were 3.1% low-risk, 26% intermediate-risk, and 70.8% high-risk cases. More than half of the patients (52.1%) had pretreatment prostate-specific antigen (PSA) >20 ng/mL. The 5-year survival outcome of low-risk, intermediate-risk, and high-risk patients were: OS, 100%, 94.7%, and 67.9% (P=0.297); and BFS, 100%, 94.1%, and 57.1% (P=0.016), respectively. In the high-risk group, the 5-year OS was 88.3% in patients who received adjuvant hormonal androgen deprivation therapy (HT), compared to 53% in RT only, P=0.08. Significant predictors of OS include high-risk group (hazard Ratio [HR], 9.35; 95% confidence interval [CI], 1.52 to 57.6; P=0.016), adjuvant therapy (HR, 0.175; 95% CI, 0.05 to 0.58; P=0.005), detection by transurethral resection of the prostate (TUR-P) (HR, 6.81; 95% CI, 2.28 to 20.33; P=0.001), and pretreatment PSA (HR, 1.003; 95% CI, 1.00 to 1.005; P=0.039). The sole predictor of biochemical failure was pretreatment PSA (P=0.04), with odds ratio of 4.52 (95% CI, 1.61 to 12.65) for PSA >20 ng/mL. Conclusions: RT is an effective treatment modality for localized or locally-advanced PCa in Indonesian patients, with outcomes and

  7. Long-Term Results of a Phase II Trial of Ultrasound-Guided Radioactive Implantation of the Prostate for Definitive Management of Localized Adenocarcinoma of the Prostate (RTOG 98-05)

    SciTech Connect

    Lawton, Colleen A.; Hunt, Daniel; Lee, W. Robert; Gomella, Leonard; Grignon, David; Gillin, Michael; Morton, Gerard; Pisansky, Thomas M.; Sandler, Howard

    2011-09-01

    Purpose: To evaluate the long-term effectiveness of transrectal ultrasound-guided permanent radioactive I{sup 125} implantation of the prostate for organ confined adenocarcinoma of the prostate compared with historical data of prostatectomy and external beam radiotherapy within a cooperative group setting. Methods and Materials: Patients accrued to this study had histologically confirmed, locally confined adenocarcinoma of the prostate clinical stage T1b, T1c, or T2a; no nodal or metastatic disease; prostate-specific antigen level of {<=}10 ng/ml; and a Gleason score of {<=}6. All patients underwent transrectal ultrasound-guided radioactive I{sup 125} seed implantation into the prostate. The prescribed dose was 145 Gy to the prostate planning target volume. Results: A total of 101 patients from 27 institutions were accrued to this protocol; by design, no single institution accrued more than 8 patients. There were 94 eligible patients. The median follow up was 8.1 years (range, 0.1-9.2 years). After 8 years, 8 patients had protocol-defined biochemical (prostate-specific antigen) failure (cumulative incidence, 8.0%); 5 patients had local failure (cumulative incidence, 5.5%); and 1 patient had distant failure (cumulative incidence, 1.1%; this patient also had biochemical failure and died of causes not related to prostate cancer). The 8-year overall survival rate was 88%. At last follow-up, no patient had died of prostate cancer or related toxicities. Three patients had maximum late toxicities of Grade 3, all of which were genitourinary. No Grade 4 or 5 toxicities were observed. Conclusions: The long-term results of this clinical trial have demonstrated that this kind of trial can be successfully completed through the RTOG and that results in terms of biochemical failure and toxicity compare very favorably with other brachytherapy published series as well as surgical and external beam radiotherapy series. In addition, the prospective, multicenter design highlights the

  8. AB38. Microorganisms in Chronic prostatitis in outpatient clinic Mongolia

    PubMed Central

    Samdankhuu, Khongorzul; Sanjmyatav, Purevjal; Damiran, Naransukh; Naidan, Nansalmaa

    2014-01-01

    Background Recent years, morbidity of chronic prostatis is increasing in Mongolia. Most common cause of the chronic prostatis is Non-Gonococcal Urethritis (NGU) such as chlamydia trachomatis, mycoplasma hominis, mycoplasma genitalium, ureaplasma urealyticum and ureaplasma parvum or mixed infections. Purpose The purpose of the study was to research possible relationships between signs or symptoms of the chronic prostatitis and its cause. Method A total of 466 males who have possible signs of chronic prostatitis were enrolled in the study. All patients were checked for urinalysis and expressed prostate secretion (EPS) and Polymerase Chain Reaction (PCR) of EPS detection for neisser a gonorrhea, chlamydia trachomatis, mycoplasma hominis, mycoplasma genitalium, ureaplasma urealyticum and ureaplasma parvum at an outpatient center of andrology office, Ulaanbaatar, Mongolia. Results Two hundred and eighty three of all participants have positive PCR results. Mean age of in our study was 33.1±8 years. U. realyticum was the most common (48.6%), followed by M. hominis and C. trachomatis mixed infection. In Mach, April and August were highest episodes of morbidity were registered 16.2%, 11.69% and 10.71%. Chronic pelvic pain syndrome and lower urinary tract symptoms were the most common complaints of main reason to visit outpatient clinic. Conclusions U. urealyticum was most common infection detected by PCR analyses among men who have chronic prostatitis, who have chronic pelvic pain syndrome. Further research is needed to determine if there are associations between signs or symptoms and cause of the chronic prostatis.

  9. A Comprehensive Review of Contemporary Role of Local Treatment of the Primary Tumor and/or the Metastases in Metastatic Prostate Cancer

    PubMed Central

    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

  10. 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.

  11. A prospective study of the efficacy of magnetic resonance spectroscopy imaging for predicting locally advanced prostate cancer

    PubMed Central

    Razi, Ali; Parizi, Mehdi Kardoust; Kazemeini, Seid Mohammad; Abedi, Akbar

    2015-01-01

    Objective: To evaluate the efficacy of magnetic resonance spectroscopy imaging (MRSI) for predicting locally advanced prostate cancer (PC). Materials and methods: Between April 2009 and July 2012, 80 consecutive patients with clinically localized PC had undergone endorectal MRSI before radical retropubic prostatectomy. Clinicopathological parameters, including age, preoperative prostate-specific antigen (PSA), Gleason score (GS) at biopsy, perinural invasion at biopsy, prostate weight at surgery, GS of surgical specimen, and pathological staging were recorded. The MRSI findings were compared with the histopathological findings of the radical prostatectomy. The diagnostic accuracy measures consisting of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of MRSI, and other variables in the diagnosis of locally advanced PC (Pathology Stages pT3a, pT3b, or pT4) were evaluated. Results: Sensitivity, specificity, PPV, and NPV of MRSI in detecting locally advanced PC is 42.4%, 93.6%, 82.3%, and 69.8%, respectively [area under the receiver operating characteristic (ROC) curve=0.658, p value <0.0001]. MRSI, cancer-positive core percentage at biopsy, and GS at biopsy are more accurate factors among all the predictive variables in predicting locally advanced PC. Conclusion: MRSI may be considered as a complementary diagnostic modality with high specificity and moderate sensitivity in predicting locally advanced PC. Combination of this modality with other predictive factors helps the surgeon and patient to select an appropriate treatment strategy. PMID:26328204

  12. 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.

  13. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer.

    PubMed

    Hamdy, Freddie C; Donovan, Jenny L; Lane, J Athene; Mason, Malcolm; Metcalfe, Chris; Holding, Peter; Davis, Michael; Peters, Tim J; Turner, Emma L; Martin, Richard M; Oxley, Jon; Robinson, Mary; Staffurth, John; Walsh, Eleanor; Bollina, Prasad; Catto, James; Doble, Andrew; Doherty, Alan; Gillatt, David; Kockelbergh, Roger; Kynaston, Howard; Paul, Alan; Powell, Philip; Prescott, Stephen; Rosario, Derek J; Rowe, Edward; Neal, David E

    2016-10-13

    Background The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. Methods We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. Results There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0

  14. High-Intensity Focused Ultrasound (HIFU) in Localized Prostate Cancer Treatment

    PubMed Central

    Alkhorayef, Mohammed; Mahmoud, Mustafa Z.; Alzimami, Khalid S.; Sulieman, Abdelmoneim; Fagiri, Maram A.

    2015-01-01

    Summary Background High-intensity focused ultrasound (HIFU) applies high-intensity focused ultrasound energy to locally heat and destroy diseased or damaged tissue through ablation. This study intended to review HIFU to explain the fundamentals of HIFU, evaluate the evidence concerning the role of HIFU in the treatment of prostate cancer (PC), review the technologies used to perform HIFU and the published clinical literature regarding the procedure as a primary treatment for PC. Material/Methods Studies addressing HIFU in localized PC were identified in a search of internet scientific databases. The analysis of outcomes was limited to journal articles written in English and published between 2000 and 2013. Results HIFU is a non-invasive approach that uses a precisely delivered ultrasound energy to achieve tumor cell necrosis without radiation or surgical excision. In current urological oncology, HIFU is used clinically in the treatment of PC. Clinical research on HIFU therapy for localized PC began in the 1990s, and the majority of PC patients were treated with the Ablatherm device. Conclusions HIFU treatment for localized PC can be considered as an alternative minimally invasive therapeutic modality for patients who are not candidates for radical prostatectomy. Patients with lower pre-HIFU PSA level and favourable pathologic Gleason score seem to present better oncologic outcomes. Future advances in technology and safety will undoubtedly expand the HIFU role in this indication as more of patient series are published, with a longer follow-up period. PMID:25806099

  15. Obesity does not promote tumorigenesis of localized patient-derived prostate cancer xenografts

    PubMed Central

    Ascui, Natasha; Frydenberg, Mark; Risbridger, Gail P.; Taylor, Renea A.; Watt, Matthew J.

    2016-01-01

    There are established epidemiological links between obesity and the severity of prostate cancer. We directly tested this relationship by assessing tumorigenicity of patient-derived xenografts (PDXs) of moderate-grade localized prostate cancer in lean and obese severe combined immunodeficiency (SCID) mice. Mice were rendered obese and insulin resistant by high-fat feeding for 6 weeks prior to transplantation, and PDXs were assessed 10 weeks thereafter. Histological analysis of PDX grafts showed no differences in tumor pathology, prostate-specific antigen, androgen receptor and homeobox protein Nkx-3.1 expression, or proliferation index in lean versus obese mice. Whilst systemic obesity per se did not promote prostate tumorigenicity, we next asked whether the peri-prostatic adipose tissue (PPAT), which covers the prostate anteriorly, plays a role in prostate tumorigenesis. In vitro studies in a cellularized co-culture model of stromal and epithelial cells demonstrated that factors secreted from human PPAT are pro-tumorigenic. Accordingly, we recapitulated the prostate-PPAT spatial relationship by co-grafting human PPAT with prostate cancer in PDX grafts. PDX tissues were harvested 10 weeks after grafting, and histological analysis revealed no evidence of enhanced tumorigenesis with PPAT compared to prostate cancer grafts alone. Altogether, these data demonstrate that prostate cancer tumorigenicity is not accelerated in the setting of diet-induced obesity or in the presence of human PPAT, prompting the need for further work to define the at-risk populations of obesity-driven tumorigenesis and the biological factors linking obesity, adipose tissue and prostate cancer pathogenesis. PMID:27351281

  16. 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.

  17. ["Expanded prostate cancer index composite" (EPIC-26): Results of functional treatment in patients with localized prostate cancer].

    PubMed

    Beyer, B; Huland, H; Feick, G; Graefen, M

    2015-11-01

    The standardized collation of the quality of treatment is a subject of discussion both nationally and internationally. This article presents the work of the International Consortium for Health Outcomes Measurement (ICHOM) and the validated German translation of the expanded prostate cancer index composite (EPIC-26). This questionnaire allows a standardized interdisciplinary collation of the quality of treatment for all therapy modalities of localized prostate cancer. Use of the ICHOM standard set and the EPIC-26 achieves a possibility for comparison of each form of therapy with respect to the curative success and the effect on health and quality of life of patients.

  18. 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.

  19. 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

  20. 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

  1. 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.

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

    PubMed Central

    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 goal of this study was 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 & ERα) epithelial cells were more prevalent in BPH, and fewer double negative (AR & 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. PMID:23792768

  3. 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

  4. Role of Intensity-Modulated Radiotherapy in Reducing Toxicity in Dose Escalation for Localized Prostate Cancer

    SciTech Connect

    Al-Mamgani, Abrahim Heemsbergen, Wilma D.; Peeters, Stephanie T.H.; Lebesque, Joos V.

    2009-03-01

    Purpose: To compare the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer patients treated to a total dose of 78 Gy with either a three-conformal radiotherapy technique with a sequential boost (SEQ) or a simultaneous integrated boost using intensity-modulated radiotherapy (SIB-IMRT). Patients and Methods: A total of 78 prostate cancer patients participating in the randomized Dutch trial comparing 68 Gy and 78 Gy were the subject of this analysis. They were all treated at the same institution to a total dose of 78 Gy. The median follow-up was 76 and 56 months for the SEQ and SIB-IMRT groups, respectively. The primary endpoints were acute and late GI and GU toxicity. Results: A significantly lower incidence of acute Grade 2 or greater GI toxicity occurred in patients treated with SIB-IMRT compared with SEQ (20% vs. 61%, p = 0.001). For acute GU toxicity and late GI and GU toxicity, the incidence was lower after SIB-IMRT, but these differences were not statistically significant. No statistically significant difference were found in the 5-year freedom from biochemical failure rate (Phoenix definition) between the two groups (70% for the SIB-IMRT group vs. 61% for the SEQ group, p = 0.3). The same was true for the 5-year freedom from clinical failure rate (90% vs. 72%, p = 0.07). Conclusion: The results of our study have shown that SIB-IMRT reduced the toxicity without compromising the outcome in patients with localized prostate cancer treated to 78 Gy radiation.

  5. 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

  6. 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

  7. Focal therapy for localized unifocal and multifocal prostate cancer: A prospective development study using real time MR guided focused ultrasound

    NASA Astrophysics Data System (ADS)

    Napoli, A.; Caliolo, G.; Boni, F.; Anzidei, M.; Catalano, C.

    2017-03-01

    To assess safety and feasibility of non-invasive high intensity 3T MR guided focused ultrasound (MRgFUS) treatment of localized prostate cancer in an exploratory designed study. Men aged 45-80 years were eligible for this prospective study if they had low-risk localized prostate cancer (prostate specific antigen [PSA] ≤10 ng/mL, Gleason score ≤ 3 + 3), with no previous androgen deprivation or treatment for prostate cancer, and who could safely undergo multiparametric MRI (Discovery 750, GE; Gd-Bopta, Bracco) and have a spinal anesthetic. Patients underwent focal therapy using real time MR guided high intensity focused ultrasound (MRgFUS), delivered to all known cancer lesions, with a margin of normal tissue. Primary endpoints were adverse events (serious and otherwise) and urinary symptoms and erectile function assessed using patient questionnaires. 8 men were recruited between June 2011 and June 2012. After treatment, one man was admitted to hospital for acute urinary retention. Another patient had self-resolving, mild, intermittent dysuria (median duration 5.0 days). Urinary tract infection was not reported. Urinary debris occurred in 6 men (75%), with a median duration of 12 days. Median overall International Index of Erectile Function-15 (IIEF-15) scores were similar at baseline and at 6 to 12 months (p=0.060), as were median IIEF-15 scores for intercourse satisfaction (p=0.433), sexual desire (p=0.622), and overall satisfaction (p=0.256). There was an improvement in lower urinary tract symptoms, assessed by International Prostate Symptom Score (IPSS), between baseline and 6 to 12 months (p=0.026). All 8 men with no baseline urinary incontinence were leak-free and pad-free by 9 months. No histological evidence of cancer was identified in 7 of 8 men biopsied at 6 months (87,5%); overall, the entire population (8 patients) was free of clinically significant cancer and had no evidence of disease on multi-parametric MRI at 6 to 12 months. MR guided Focused

  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. HIFU therapy for local recurrence of prostate cancer after external beam radiotherapy and radical prostatectomy - 5,5 years experience

    NASA Astrophysics Data System (ADS)

    Solovov, V. A.; Vozdvizhenskiy, M. O.; Matysh, Y. S.

    2017-03-01

    Objectives. To evaluate the clinical efficacy of high-intensity focused ultrasound ablation (HIFU) for local recurrence of prostate cancer after external beam radiotherapy (EBRT) and radical prostatectomy (RPE). Materials and Methods: During 2007-2013 years 47 patients with local recurrence of prostate cancer after EBRT and RPE undertook HIFU therapy on the system "Ablaterm» (EDAP, France). Relapse arose after an average of 2 years after EBRT and RPE. Median follow-up after HIFU therapy was 38 (12-60) months. The mean age was 68.5 ± 5.8 years. The median PSA level before HIFU - 15.4 (7-48) ng / mL. Results: In 34 patients (72.3%) at six months after treatment the median PSA was 0.4 (0-3.2) ng / mL, in 48 months - 0.9 (0.4-7.5) ng / mL. In 13 patients (27.7%) at 6 months was observed progression of the disease. In general, after a 5-year follow-up 72.3% of the patients had no data for the progression and recurrence. Conclusion: HIFU therapy in patients with local recurrence of prostate cancer after EBRT and RPE is minimally invasive and effective technology.

  10. Prostate cancer chemoprevention: Strategies for designing efficient clinical trials.

    PubMed

    Lieberman, R

    2001-04-01

    A chemoprevention (CP) strategy has evolved for conducting efficient clinical trials for prostate cancer (PCa) prevention. It integrates five key components, including agents, biomarkers, cohorts, designs, and endpoints. The rationale for the CP strategy relates to the natural history of prostate cancer. There is a wide array of natural and synthetic agents that hold promise for inhibiting, reversing, or modulating the transition from normal to precancer and from precancer to cancer. These agent classes include antiandrogens, antiestrogens, phytoestrogens, antioxidants, anti-inflammatory (proapoptotic) agents, antiproliferation/antidifferentiation agents, signal transduction modulators of receptor tyrosine kinase and ras farnesylation, antiangiogenesis agents, insulinlike growth factor (IGF)-1, peroxisome proliferator-activator receptor modulators (-gamma and -delta), and gene-based interventions. Biomarkers and endpoints are guided by the level of evidence required (eg, phase 1, 2, 3). Two candidate surrogate endpoints (SE) based on histology are high-grade prostatic intraepithelial neoplasia (HGPIN) and computer-assisted image analysis of dysplastic lesions. Phase 1 trials use standard endpoints of safety, pharmacokinetics and limited pharmacodynamics. Phase 2 trials use endpoints of modulation of biomarkers and correlation with histology. Phase 3 trials use endpoints of clinical benefit, such as cancer incidence reduction and quality of life. Validation of a biomarker as a SE involves correlation of the biomarker with clinical benefit. Cohorts (target populations) for phase 2/3 trials include the general population of men over age 50 with a normal prostate-specific antigen (PSA), subjects with a strong family history of PCa, subjects with elevated PSA/negative biopsy, and subjects with HGPIN/negative biopsy. These at-risk populations reflect key individual risk factors (age, race, serum PSA [free/total]; serum IGF-1/IGF binding protein (IGFBP)-3; 1, 25(OH)(2) D3

  11. 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

  12. Noninvasive Localization of Prostate Cancer via Diffusion Sensitive MRI

    DTIC Science & Technology

    2008-03-01

    sequence, Haker et al and Roebuck et al using a line-scan diffusion sequence, and Vigneron et al using a fast spin-echo diffusion sequence (33,35-37...Mulkern RV, Haker S, Zhang J, Zou KH, Maier SE, Tempany CM. Detection of prostate cancer by integration of line-scan diffusion, T2-mapping and T2-weighted...36. Haker SJ, Szot Barnes A, Maier SE, Tempany CM, Mulkern RV. Diffusion Tensor Imaging for Prostate Cancer Detection: Preliminary Results from a

  13. 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

  14. 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.

  15. 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

  16. 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.

  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. 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

  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. Clinical significance of incidental FDG uptake in the prostate gland detected by PET/CT

    PubMed Central

    Sahin, Ertan; Elboga, Umut; Kalender, Ebuzer; Basıbuyuk, Mustafa; Demir, Hasan Deniz; Celen, Yusuf Zeki

    2015-01-01

    The value of FDG-positron emission tomography/computed tomography (PET/CT) for detecting prostate cancer is unknown. We aimed to investigate the clinical value of incidental prostate FDG uptake on PET/CT scans. We reviewed 6128 male patients who underwent FDG-PET/CT scans and selected cases that reported hypermetabolic lesion in the prostate. The patients who have prior history of prostate carcinoma or prostate surgery were excluded from the study. We have analyzed the correlation between PET/CT findings and serum prostate-specific antigen (PSA) levels, imaging (USG), urological examinations and biopsy. Incidental 18F-FDG uptake of the prostate gland was observed in 79 patients (1.3%). While sixteen of them were excluded due to inadequate clinical data, the remaining 63 patients were included for further analysis. The patients were divided into two groups; 8 patients (12.7%) in the malignant group and 55 patients (87.3%) in the benign group. The SUVmax values were not significantly different between the two groups. In 6 (75%) patients with prostate cancer, FDG uptake was observed focally in the peripheral zone of the prostate glands. There was no significant correlation between the SUVmax and the PSA levels. Incidental 18F-FDG uptake in the prostate gland is a rare condition, but a substantial portion of it is associated with the cancer. Benign and malignant lesions of the prostate gland in FDG-PET/CT imaging could not be reliably distinguished. The peripheral focally FDG uptake of prostate glands should be further examined with the clinical and labaratory evaluations. PMID:26379847

  1. 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.

  2. Expert consensus document: Semantics in active surveillance for men with localized prostate cancer - results of a modified Delphi consensus procedure.

    PubMed

    Bruinsma, Sophie M; Roobol, Monique J; Carroll, Peter R; Klotz, Laurence; Pickles, Tom; Moore, Caroline M; Gnanapragasam, Vincent J; Villers, Arnauld; Rannikko, Antti; Valdagni, Riccardo; Frydenberg, Mark; Kakehi, Yoshiyuki; Filson, Christopher P; Bangma, Chris H

    2017-03-14

    Active surveillance (AS) is broadly described as a management option for men with low-risk prostate cancer, but semantic heterogeneity exists in both the literature and in guidelines. To address this issue, a panel of leading prostate cancer specialists in the field of AS participated in a consensus-forming project using a modified Delphi method to reach international consensus on definitions of terms related to this management option. An iterative three-round sequence of online questionnaires designed to address 61 individual items was completed by each panel member. Consensus was considered to be reached if ≥70% of the experts agreed on a definition. To facilitate a common understanding among all experts involved and resolve potential ambiguities, a face-to-face consensus meeting was held between Delphi survey rounds two and three. Convenience sampling was used to construct the panel of experts. In total, 12 experts from Australia, France, Finland, Italy, the Netherlands, Japan, the UK, Canada and the USA participated. By the end of the Delphi process, formal consensus was achieved for 100% (n = 61) of the terms and a glossary was then developed. Agreement between international experts has been reached on relevant terms and subsequent definitions regarding AS for patients with localized prostate cancer. This standard terminology could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making.

  3. 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

  4. [Androgen-deprivation therapy in prostate cancer: clinical evidence and future perspectives].

    PubMed

    Pinto, F; Calarco, A; Totaro, A; Sacco, E; Volpe, A; Racioppi, M; D'Addessi, A; Bassi, P F

    2010-01-01

    Androgens are involved in the development and progression of prostate cancer even if the mechanism is not well-recognized. For this reason androgen-deprivation therapy remains a milestone for the treatment of patients with advanced and metastatic disease and, in the last years, in conjunction with radiotherapy and surgery in locally advanced tumors. Alternative options, such as intermittent deprivation suppression, seem to be promising in terms of clinical benefits and toxicity profile. However, current therapies present side effects, such as testosterone surge with consequent clinical flare-up, metabolic syndrome and hormone-resistance, which develops after a variable number of years. Novel therapies such as LH-RH antagonists and prolonged depot LH-RH analogues have been developed in order to avoid clinical flare-up and testosterone microsurges. Novel androgen synthesis inhibitors, such as abiraterone acetate and MDV3100, have been recently discovered and tested as promising hormonal second-line agents in patients with castration-resistant prostate cancer. Finally, long-term side effects from androgen deprivation, such as osteoporosis, sarcopenic obesity and cardiovascular morbidity should be carefully monitored and properly treated.

  5. [Clinical and pathomorphological features of chronic prostatitis in chemical industry workers].

    PubMed

    Neimark, A I; Kiptilov, A V; Lapiy, G A

    2015-12-01

    During periodic screening on the chemical industry, an increased incidence of chronic prostatitis in workers at sulfuric acid section was revealed. Detailed examination has revealed features of the clinical picture of the pathological process that develops in the prostate gland of workers exposed to harmful labor conditions. Complex pathomorphologic analysis of prostate biopsies of workers with chronic abacterial prostatitis found fundamental differences of morphological manifestations observed in other forms of chronic prostatitis. They include the prevalence of dystrophic and atrophic changes of glandular components with the presence of focuses of simple and small acinar atrophy, reduction of the microvasculature vessels, progressive fibrosis of the stroma with the phenomena of periglandular and perivascular sclerosis, as a rule, in the absence of inflammatory cell infiltration. Doppler ultrasound data indicated a change in hemodynamics, accompanied by a decrease in blood flow in the prostate gland.

  6. Biomarkers for Early Detection of Clinically Relevant Prostate Cancer: A Multi-Institutional Validation Trial

    DTIC Science & Technology

    2015-10-01

    1 1 AWARD NUMBER: W81XWH-14-1-0596 TITLE: Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A Multi-Institutional...Validation Trial PRINCIPAL INVESTIGATOR: Jesse McKenney, MD CONTRACTING ORGANIZATION: Cleveland Clinic Foundation Cleveland, OH 44195 REPORT DATE...COVERED 30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A

  7. Chronic prostatitis

    PubMed Central

    2011-01-01

    Introduction Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome [CP/CPPS]). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for chronic bacterial prostatitis? What are the effects of treatments for chronic abacterial prostatitis/chronic pelvic pain syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 33 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: 5 alpha-reductase inhibitors, allopurinol, alpha-blockers, biofeedback, local injections of antimicrobial drugs, mepartricin, non-steroidal anti-inflammatory drugs (NSAIDs), oral antimicrobial drugs, pentosan polysulfate, prostatic massage, quercetin, radical prostatectomy, sitz baths, transurethral microwave thermotherapy, and transurethral resection. PMID:21736764

  8. Prostate clinical study of a full inversion unconstrained ultrasound elastography technique

    NASA Astrophysics Data System (ADS)

    Mousavi, S. Reza; Sadeghi-Naini, Ali; Czarnota, Gregory J.; Samani, Abbas

    2014-03-01

    Prostate cancer detection at early stages is crucial for desirable treatment outcome. Among available imaging modalities, ultrasound (US) elastography is being developed as an effective clinical tool for prostate cancer diagnosis. Current clinical US elastography systems utilise strain imaging where tissue strain images are generated to approximate the tissue elastic modulus distribution. While strain images can be generated in real-time fashion, they lack the accuracy necessary for having desirable sensitivity and specificity. To improve strain imaging, full inversion based elastography techniques were proposed. Among these techniques, a constrained elastography technique was developed which showed promising results as long as the tumor and prostate geometry can be obtained accurately from the imaging modality used in conjunction with the elastography system. This requirement is not easy to fulfill, especially with US imaging. To address this issue, we present an unconstrained full inversion prostate elastography method in conjunction with US imaging where knowledge of tissue geometry is not necessary. One of the reasons that full inversion elastography techniques have not been routinely used in the clinic is lack of clinical validation studies. To our knowledge, no quasistatic full inversion based prostate US elastography technique has been applied in vivo before. In this work, the proposed method was applied to clinical prostate data and reconstructed elasticity images were compared to corresponding annotated histopathology images which is the first quasi-static full inversion based prostate US elastography technique applied successfully in vivo. Results demonstrated a good potential for clinical utility of the proposed method.

  9. Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications.

    PubMed

    Sun, Fei; Crisóstomo, Verónica; Báez-Díaz, Claudia; Sánchez, Francisco M

    2016-01-01

    Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.

  10. Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications

    SciTech Connect

    Sun, Fei Crisóstomo, Verónica Báez-Díaz, Claudia Sánchez, Francisco M.

    2016-01-15

    Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.

  11. 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.

  12. 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.

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

    PubMed Central

    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

    2016-01-01

    Abstract 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

  14. 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.

  15. PTEN deletion and heme oxygenase-1 overexpression cooperate in prostate cancer progression and are associated with adverse clinical outcome.

    PubMed

    Li, Yunru; Su, Jie; DingZhang, Xiao; Zhang, Jianguo; Yoshimoto, Maisa; Liu, Shuhong; Bijian, Krikor; Gupta, Ajay; Squire, Jeremy A; Alaoui Jamali, Moulay A; Bismar, Tarek A

    2011-05-01

    Overexpression of the pro-survival protein heme oxygenase-1 (HO-1) and loss of the pro-apoptotic tumour suppressor PTEN are common events in prostate cancer (PCA). We assessed the occurrence of both HO-1 expression and PTEN deletion in two cohorts of men with localized and castration-resistant prostate cancer (CRPC). The phenotypic cooperation of these markers was examined in preclinical and clinical models. Overall, there was a statistically significant difference in HO-1 epithelial expression between benign, high-grade prostatic intraepithelial neoplasia (HGPIN), localized PCA, and CRPC (p < 0.0001). The highest epithelial HO-1 expression was noted in CRPC (2.00 ± 0.89), followed by benign prostate tissue (1.49 ± 1.03) (p = 0.0003), localized PCA (1.20 ± 0.95), and HGPIN (1.07 ± 0.87) (p < 0.0001). However, the difference between HGPIN and PCA was not statistically significant (p = 0.21). PTEN deletions were observed in 35/55 (63.6%) versus 68/183 (37.1%) cases of CRPC and localized PCA, respectively. Although neither HO-1 overexpression nor PTEN deletions alone in localized PCA showed a statistically significant association with PSA relapse, the combined status of both markers correlated with disease progression (log-rank test, p = 0.01). In a preclinical model, inhibition of HO-1 by shRNA in PTEN-deficient PC3M cell line and their matched cells where PTEN is restored strongly reduced cell growth and invasion in vitro and inhibited tumour growth and lung metastasis formation in mice compared to cells where only HO-1 is inhibited or PTEN is restored. In summary, we provide clinical and experimental evidence for cooperation between epithelial HO-1 expression and PTEN deletions in relation to the PCA patient's outcome. These findings could potentially lead to the discovery of novel therapeutic modalities for advanced PCA.

  16. 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

  17. Evaluation of an Epithelial Plasticity (EP) Biomarker Panel in Men with Localized Prostate Cancer

    PubMed Central

    Armstrong, Andrew J; Healy, Patrick; Halabi, Susan; Vollmer, Robin; Lark, Amy; Kemeny, Gabor; Ware, Kathryn; Freedland, Stephen J.

    2015-01-01

    Background Given the potential importance of epithelial plasticity (EP) to cancer metastasis, we sought to investigate biomarkers related to EP in men with localized prostate cancer (PC) for the association with time to PSA recurrence and other clinical outcomes after surgery. Methods Men with localized PC treated with radical prostatectomy at the Durham VA medical center and whose prostatectomy tissues were included in a tissue microarray (TMA) linked to long-term outcomes. We performed immunohistochemical studies using validated antibodies against E-cadherin and Ki-67 and mesenchymal biomarkers including N-cadherin, vimentin, SNAIL, ZEB1, and TWIST. Association studies were conducted for each biomarker with baseline clinical/pathologic characteristics and risk of PSA recurrence over time. Results Two hundred and five men contributed TMA tissue and had long-term follow-up (median 11 years). Forty-three percent had PSA recurrence; 3 died of PC. The majority had high E-cadherin expression (86%); 14% had low/absent E-cadherin expression. N-cadherin was rarely expressed (<4%) and we were unable to identify an E-to-N cadherin switch as independently prognostic. No associations with clinical risk group, PSA recurrence, or Gleason sum were noted for SNAIL, ZEB1, vimentin, or TWIST, despite heterogeneous expression between patients. We observed an association of higher Ki-67 expression with Gleason sum (p=0.043), NCCN risk (p=0.013), and PSA recurrence (HR 1.08, p=0.0095). Conclusions The expression of EP biomarkers in this cohort of men with a low risk of PC-specific mortality was not associated with aggressive features or PSA relapse after surgery. PMID:26458958

  18. High-Dose-Rate Monotherapy: Safe and Effective Brachytherapy for Patients With Localized Prostate Cancer

    SciTech Connect

    Demanes, D. Jeffrey; Martinez, Alvaro A.; Ghilezan, Michel; Hill, Dennis R.; Schour, Lionel; Brandt, David; Gustafson, Gary

    2011-12-01

    Purpose: High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients. Methods and Materials: There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography-defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis-free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%. Conclusions: High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.

  19. TMPRSS2-ERG Fusion Gene Expression in Prostate Tumor Cells and Its Clinical and Biological Significance in Prostate Cancer Progression

    PubMed Central

    St. John, Jason; Powell, Katelyn; Conley-LaComb, M. Katie; Chinni, Sreenivasa R.

    2012-01-01

    TMPRSS2-Ets gene fusions were identified in prostate cancers where the promoter of transmembrane protease, serine 2 (TMPRSS2) fused with coding sequence of the erythroblastosis virus E26 (Ets) gene family members. TMPRSS2 is an androgen responsive transmembrane serine protease. Ets family members are oncogenic transcription factors that contain a highly conserved Ets DNA binding domain and an N-terminal regulatory domain. Fusion of these gene results in androgen dependent transcription of Ets factor in prostate tumor cells. The ERG is the most common fusion partner with TMPRSS2 promoter in prostate cancer patients. The high prevalence of these gene fusions, in particular TMPRSS2-ERG, makes them attractive as potential diagnostic and prognostic indicators, as well as making them a potential target for tailored therapies. This review focuses on the clinical and biological significance of TMPRSS2-ERG fusions and their role in PC development and progression. PMID:23264855

  20. Chemotherapy-induced monoamine oxidase expression in prostate carcinoma functions as a cytoprotective resistance enzyme and associates with clinical outcomes.

    PubMed

    Gordon, Ryan R; Wu, Mengchu; Huang, Chung-Ying; Harris, William P; Sim, Hong Gee; Lucas, Jared M; Coleman, Ilsa; Higano, Celestia S; Gulati, Roman; True, Lawrence D; Vessella, Robert; Lange, Paul H; Garzotto, Mark; Beer, Tomasz M; Nelson, Peter S

    2014-01-01

    To identify molecular alterations in prostate cancers associating with relapse following neoadjuvant chemotherapy and radical prostatectomy patients with high-risk localized prostate cancer were enrolled into a phase I-II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pre-treatment prostate tissue was acquired by needle biopsy and post-treatment tissue was acquired by prostatectomy. Prostate cancer gene expression measurements were determined in 31 patients who completed 4 cycles of neoadjuvant chemotherapy. We identified 141 genes with significant transcript level alterations following chemotherapy that associated with subsequent biochemical relapse. This group included the transcript encoding monoamine oxidase A (MAOA). In vitro, cytotoxic chemotherapy induced the expression of MAOA and elevated MAOA levels enhanced cell survival following docetaxel exposure. MAOA activity increased the levels of reactive oxygen species and increased the expression and nuclear translocation of HIF1α. The suppression of MAOA activity using the irreversible inhibitor clorgyline augmented the apoptotic responses induced by docetaxel. In summary, we determined that the expression of MAOA is induced by exposure to cytotoxic chemotherapy, increases HIF1α, and contributes to docetaxel resistance. As MAOA inhibitors have been approved for human use, regimens combining MAOA inhibitors with docetaxel may improve clinical outcomes.

  1. Chemotherapy-Induced Monoamine Oxidase Expression in Prostate Carcinoma Functions as a Cytoprotective Resistance Enzyme and Associates with Clinical Outcomes

    PubMed Central

    Huang, Chung-Ying; Harris, William P.; Sim, Hong Gee; Lucas, Jared M.; Coleman, Ilsa; Higano, Celestia S.; Gulati, Roman; True, Lawrence D.; Vessella, Robert; Lange, Paul H.; Garzotto, Mark; Beer, Tomasz M.; Nelson, Peter S.

    2014-01-01

    To identify molecular alterations in prostate cancers associating with relapse following neoadjuvant chemotherapy and radical prostatectomy patients with high-risk localized prostate cancer were enrolled into a phase I-II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pre-treatment prostate tissue was acquired by needle biopsy and post-treatment tissue was acquired by prostatectomy. Prostate cancer gene expression measurements were determined in 31 patients who completed 4 cycles of neoadjuvant chemotherapy. We identified 141 genes with significant transcript level alterations following chemotherapy that associated with subsequent biochemical relapse. This group included the transcript encoding monoamine oxidase A (MAOA). In vitro, cytotoxic chemotherapy induced the expression of MAOA and elevated MAOA levels enhanced cell survival following docetaxel exposure. MAOA activity increased the levels of reactive oxygen species and increased the expression and nuclear translocation of HIF1α. The suppression of MAOA activity using the irreversible inhibitor clorgyline augmented the apoptotic responses induced by docetaxel. In summary, we determined that the expression of MAOA is induced by exposure to cytotoxic chemotherapy, increases HIF1α, and contributes to docetaxel resistance. As MAOA inhibitors have been approved for human use, regimens combining MAOA inhibitors with docetaxel may improve clinical outcomes. PMID:25198178

  2. Comparison of two adjuvant hormone therapy regimens in patients with high-risk localized prostate cancer after radical prostatectomy: primary results of study CU1005.

    PubMed

    Chang, Kun; Qin, Xiao-Jian; Zhang, Hai-Liang; Dai, Bo; Zhu, Yao; Shi, Guo-Hai; Shen, Yi-Jun; Zhu, Yi-Ying; Ye, Ding-Wei

    2016-01-01

    The role of adjuvant hormonal therapy and optimized regimens for high-risk localized prostate cancer after radical prostatectomy remains controversial. Herein, the clinical trial CU1005 prospectively evaluated two regimens of maximum androgen blockage  or bicalutamide 150 mg daily as immediate adjuvant therapy for high-risk localized prostate cancer. Overall, 209 consecutive patients were recruited in this study, 107 of whom received 9 months of adjuvant maximum androgen blockage, whereas 102 received 9 months of adjuvant bicalutamide 150 mg. The median postoperative follow-up time was 27.0 months. The primary endpoint was biochemical recurrence. Of the 209 patients, 59 patients developed biochemical recurrence. There was no difference between the two groups with respect to clinical characteristics, including age, pretreatment prostate-specific antigen, Gleason score, surgical margin status, or pathological stages. The maximum androgen blockage group experienced longer biochemical recurrence-free survival (P = 0.004) compared with the bicalutamide 150 mg group. Side-effects in the two groups were similar and could be moderately tolerated in all patients. In conclusion, immediate, 9-month maximum androgen blockage should be considered as an alternative to bicalutamide 150 mg as adjuvant treatment for high-risk localized prostate cancer patients after radical prostatectomy.

  3. Sexual Rehabilitation after Localized Prostate Cancer: Current Interventions and Future Directions

    PubMed Central

    Latini, David M.; Hart, Stacey L.; Coon, David W.; Knight, Sara J.

    2011-01-01

    Many published articles have documented the impact of prostate-cancer treatment on sexual functioning in men treated for localized disease. Surprisingly, the literature on interventions to rehabilitate men’s sexual functioning is much more limited. In this article, we review the sexual-rehabilitation interventions for prostate-cancer patients and identify a number of common themes across interventions. We also identify areas where further research is needed and propose a conceptual model based on psychological and nursing theories and informed by the published research. PMID:19197171

  4. [Usefulness of urethral endoprosthesis in the management of urinary retention after brachytherapy for localized prostate cancer].

    PubMed

    Kerkeni, W; Chahwan, C; Lenormand, C; Dubray, B; Benyoucef, A; Pfister, C

    2014-03-01

    Brachytherapy is a possible treatment for localized low risk prostate cancer. Although this option is minimally invasive, some side effects may occur. Acute retention of urine (ARU) has been observed in 5% to 22% of cases and can be prevented in most cases by alpha-blocker treatment. Several alternatives have been reported in the literature for the management of ARU following brachytherapy: prolonged suprapubic catheterization, transurethral resection of the prostate and also intermittent self-catheterization. The authors report an original endoscopic approach, using urethral endoprosthesis, with a satisfactory voiding status.

  5. Intraprostatic injection of alcohol gel for the treatment of benign prostatic hyperplasia: preliminary clinical results.

    PubMed

    Larson, Benjamin T; Netto, Nelson; Huidobro, Christian; de Lima, Marcelo Lopez; Matheus, Wagner; Acevedo, Cristian; Larson, Thayne R

    2006-09-06

    Benign prostatic hyperplasia (BPH) is one of the most common diseases ailing older men. Office-based procedures offer the advantage of being more effective than medications, while limiting the adverse effects, cost, and recovery of surgery. This study presents preliminary data on a new procedure that utilizes intraprostatic alcohol gel injection to ablate prostatic tissue. The purpose of this study is to evaluate the feasibility of using this gel as a treatment for BPH. A total of 65 patients with lower urinary tract symptoms (LUTS) due to BPH were treated with intraprostatic injections of alcohol gel. The gel is composed of 97% denatured alcohol and a patented polymer to cause viscosity. Three different methods of injection were utilized: transrectal (TR) injections (8), transurethral (TU) injections (36), and transperineal (TP) injections guided by biplaned ultrasound (21). Each method provided easy access to the center of the prostate, where a volume of gel, approximately 20-30% of the prostatic volume, was injected. Follow-up was based on changes in peak urinary flow (Qmax), IPSS scores, quality of life scores (QoL), adverse effects, and failures. Data are available at 3 and 12 months. The procedure was well tolerated with only local or no anesthesia in the TR and TP groups; the TU group received spinal anesthesia. All groups showed statistically significant (p < 0.0001) improvements in Qmax, IPSS, and QoL. The mean amount of gel injected was 8.05 ml, representing 21.56% of the prostatic volume. Qmax increased from a baseline mean of 8.50 to 12.01 ml/s at 3 months, and to 11.29 ml/s at 12 months. IPSS scores improved from a baseline mean of 21.12 to 10.00 at 3 months, and to 11.84 at 12 months. QoL scores were only available for 55 patients. QoL scores improved from a baseline of 3.93 to 1.98 at 3 months, and to 2.18 at 12 months. No extraprostatic injury or adverse effects were reported due to treatment. This preliminary study presents significant results

  6. 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.

  7. Local anesthesia for transrectal ultrasound-guided biopsy of the prostate: A meta-analysis

    PubMed Central

    Li, Mingchao; Wang, Zhengyun; Li, Hao; Yang, Jun; Rao, Ke; Wang, Tao; Wang, Shaogang; Liu, Jihong

    2017-01-01

    A meta-analysis was performed to evaluate the efficacy of local anesthesia in alleviating pain during prostate biopsy. We searched relevant articles in PubMed and Embase. The included studies should be randomized controlled trials (RCT) using local anesthesia to alleviate pain during biopsy, which was recorded by a pain scale. Analgesic efficacy of different local anesthesia techniques were analyzed, including intrarectal local anesthesia (IRLA), periprostatic nerve block (PNB), pelvic plexus block (PPB) and intraprostatic local anesthesia (IPLA). We included 46 RCTs. PNB significantly reduced pain score compared with placebo (−1.27 [95% confidence interval [95% CI] −1.72, −0.82]) or no injection (−1.01 [95% CI −1.2, −0.82]). IRLA with prilocaine-lidocaine cream could also reduced pain (−0.45 [95% CI −0.76, −0.15]), while the IRLA with lidocaine gel was not effective (−0.1 [95% CI −0.24, 0.04]). PNB lateral to the neurovascular bundle had better analgesic effect than at prostate apex (P = 0.02). Combination use of PPB and IRLA considerably alleviated pain of patients compared with the combination of PNB and IRLA (−1.32 [95% CI −1.59, −1.06]). In conclusion, local anesthesia could alleviate patients’ pain during the prostate biopsy. PNB was not so effective as PPB. PMID:28079154

  8. Prognostic Value of Survivin in Locally Advanced Prostate Cancer: Study Based on RTOG 8610

    SciTech Connect

    Zhang Min; Ho, Alex; Hammond, Elizabeth H.; Suzuki, Yoshiyuki; Bermudez, R. Scott; Lee, R. Jeffrey; Pilepich, Michael; Shipley, William U.; Sandler, Howard; Khor, Li-Yan; Pollack, Alan; Chakravarti, Arnab

    2009-03-15

    Purpose: To examine the prognostic value of nuclear and cytoplasmic survivin expression in men with locally advanced prostate cancer who were enrolled in Radiation Therapy Oncology Group (RTOG) protocol 8610. Methods and Materials: RTOG 8610 was a Phase III randomized study comparing the effect of radiotherapy plus short-term androgen deprivation with radiotherapy alone. Of the 456 eligible patients, 68 patients had suitably stained tumor material for nuclear survivin analysis and 65 patients for cytoplasmic survivin. Results: Compared with patients with nuclear survivin intensity scores of {<=}191.2, those with intensity scores >191.2 had significantly improved prostate cancer survival (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.20-1.00, p = 0.0452). On multivariate analysis, nuclear survivin intensity scores >191.2 were significantly associated with improved overall survival (HR, 0.46; 95% CI, 0.25-0.86; p = 0.0156) and prostate cancer survival (HR, 0.36; 95% CI, 0.16-0.84; p = 0.0173). On univariate analysis, compared with patients with cytoplasmic survivin integrated optical density {<=}82.7, those with an integrated optical density >82.7 showed a significantly increased risk of local progression (HR, 2.49; 95% CI, 1.03-6.01; p = 0.0421). Conclusion: Nuclear overexpression of survivin was associated with improved overall and prostate cancer survival on multivariate analysis, and cytoplasmic overexpression of survivin was associated with increased rate of local progression on univariate analysis in patients with locally advanced prostate cancer treated on RTOG 8610. Our results might reflect the different functions of survivin and its splice variants, which are known to exist in distinct subcellular compartments.

  9. 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

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

    ClinicalTrials.gov

    2016-12-06

    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

  11. 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

  12. Multiparametric magnetic resonance imaging of the prostate: technical aspects and role in clinical management.

    PubMed

    Costa, Daniel N; Pedrosa, Ivan; Roehrborn, Claus; Rofsky, Neil M

    2014-08-01

    The heterogeneity and largely indolent nature of prostate cancer require better tools to avoid overdetection of low-risk disease and improve diagnostic accuracy in high-risk patients. During the last 3 decades, magnetic resonance imaging (MRI) has evolved to become the most accurate imaging technique for prostate cancer detection and staging, with a promising role in risk stratification. Because each MRI technique has advantages and limitations, state of the art of the so-called multiparametric MRI of the prostate is achieved combining anatomical T2-weighted imaging integrated with other techniques in which image contrast is related to the pathophysiology of the disease, such as diffusion-weighted imaging, dynamic contrast-enhanced imaging, and MR spectroscopy. After reviewing this article, readers will understand the clinical challenges in the management of patients with confirmed or suspected prostate cancer, when and how multiparametric MRI of the prostate can provide meaningful information, and how to perform and interpret it.

  13. An audit of prostate-specific antigen and clinical symptoms in general practice.

    PubMed Central

    Ramachandran, S.; Foster, M. C.; Thomas, D. R.; Roalfe, A. K.; Hall, R. A.

    1998-01-01

    The objective was to devise local guidelines for the referral of patients with suspected prostatic carcinoma following evaluation by a retrospective audit of the value of the prostate-specific antigen concentration, together with age, urological symptoms, and digital rectal examination in the diagnosis of carcinoma of the prostate. Relevant details were collected from the notes of 582 patients from general practice and hospital. The significant diagnostic factors were ascertained by stepwise logistic regression. Prostate-specific antigen concentration, digital rectal examination and significant terminal dribbling were the most powerful factors in the diagnosis of carcinoma of the prostate. When prostate-specific antigen concentration was considered in isolation, a value of 6.5 ng/ml appeared appropriate for referral. Age was not significant, perhaps due to the narrow patient age range. The significant diagnostic factors were built into an algorithm calculating the probability of carcinoma of the prostate. This algorithm, together with prostate-specific antigen concentration results and digital rectal examination findings, forms the basis of the referral guidelines and a subsequent prospective study. PMID:9538483

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. Updated results of a phase I trial of motexafin lutetium-mediated interstitial photodynamic therapy in patients with locally recurrent prostate cancer.

    PubMed

    Verigos, Kosmas; Stripp, Diana C Hsiung; Mick, Rosemarie; Zhu, Timothy C; Whittington, Richard; Smith, Debbie; Dimofte, Andreea; Finlay, Jarod; Busch, Theresa M; Tochner, Zelig A; Malkowicz, S; Glatstein, Eli; Hahn, Stephen M

    2006-01-01

    Locally recurrent prostate cancer after treatment with radiation therapy is a clinical problem with few acceptable treatments. One potential treatment, photodynamic therapy (PDT), is a modality that uses laser light, drug photosensitizer, and oxygen to kill tumor cells through direct cellular cytotoxicity and/or through destruction of tumor vasculature. A Phase I trial of interstitial PDT with the photosensitizer Motexafin lutetium was initiated in men with locally recurrent prostate cancer. In this ongoing trial, the primary objective is to determine the maximally tolerated dose of Motexafin lutetium-mediated PDT. Other objectives include evaluation of Motexafin lutetium uptake from prostate tissue using a spectrofluorometric assay and evaluation of optical properties in the human prostate. Fifteen men with biopsy-proven locally recurrent prostate cancer and no evidence of distant metastatic disease have been enrolled and 14 have been treated. Treatment plans were developed using transrectal ultrasound images. The PDT dose was escalated by increasing the Motexafin lutetium dose, increasing the 732 ran light dose, and decreasing the drug-light interval. Motexafin lutetium doses ranged from 0.5 to 2 mg/kg administered IV 24, 6, or 3 hr prior to 732 ran light delivery. The light dose, measured in real time with in situ spherical detectors was 25-100 J/cm2. Light was delivered via optical fibers inserted through a transperineal brachytherapy template in the operating room. 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. Fourteen patients have completed protocol treatment on eight dose levels without dose-limiting toxicity. Grade I genitourinary symptoms that are PDT related have been observed. One patient had Grade II urinary urgency that was urinary catheter related. No rectal or other gastrointestinal PDT-related tox

  20. 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

  1. LIGHT: A Novel Immunotherapy for Primary and Metastatic Prostate Cancer

    DTIC Science & Technology

    2014-09-01

    effects due to the loss of testosterone (including fatigue, decreased sexual desire, weight gain, loss of muscle mass and osteoporosis ) and the well...beyond the prostate, immunotherapy may be the only way to treat it [6, 7]. A majority of clinical trials for the immunotherapy of prostate cancer...Localized Prostate Cancer. J Sex Med, 2012. 5. Fitzpatrick, J.M., Management of localized prostate cancer in senior adults : the crucial role of comorbidity

  2. Biomarkers for Early Detection of Clinically Relevant Prostate Cancer: A Multi-Institutional Validation Trial

    DTIC Science & Technology

    2015-10-01

    diagnosed with early stage prostate cancer a critical need exists for molecular assays that accurately distinguish aggressive prostate cancer from those...their ability to distinguish aggressive cancers from indolent cancers. We have established agreements with three commercial companies to analyze their...in clinical practice to predict aggressive disease. The accuracy of each biomarker for predicting short- and long-term progression will be

  3. 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

  4. Patient-Reported Outcomes After 3-Dimensional Conformal, Intensity-Modulated, or Proton Beam Radiotherapy for Localized Prostate Cancer

    PubMed Central

    Gray, Phillip J.; Paly, Jonathan J.; Yeap, Beow Y.; Sanda, Martin G.; Sandler, Howard. M.; Michalski, Jeff M.; Talcott, James A.; Coen, John J.; Hamstra, Daniel A.; Shipley, William U.; Hahn, Stephen M.; Zietman, Anthony L.; Bekelman, Justin E.; Efstathiou, Jason A.

    2013-01-01

    BACKGROUND Recent studies have suggested differing toxicity patterns for patients with prostate cancer who receive treatment with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), or proton beam therapy (PBT). METHODS The authors reviewed patient-reported outcomes data collected prospectively using validated instruments that assessed bowel and urinary quality of life (QOL) for patients with localized prostate cancer who received 3DCRT (n = 123), IMRT (n = 153) or PBT (n = 95). Clinically meaningful differences in mean QOL scores were defined as those exceeding half the standard deviation of the baseline mean value. Changes from baseline were compared within groups at the first post-treatment follow-up (2–3 months from the start of treatment) and at 12 months and 24 months. RESULTS At the first post-treatment follow-up, patients who received 3DCRT and IMRT, but not those who received PBT, reported a clinically meaningful decrement in bowel QOL. At 12 months and 24 months, all 3 cohorts reported clinically meaningful decrements in bowel QOL. Patients who received IMRT reported clinically meaningful decrements in the domains of urinary irritation/obstruction and incontinence at the first post-treatment follow-up. At 12 months, patients who received PBT, but not those who received IMRT or 3DCRT, reported a clinically meaningful decrement in the urinary irritation/ obstruction domain. At 24 months, none of the 3 cohorts reported clinically meaningful changes in urinary QOL. CONCLUSIONS Patients who received 3DCRT, IMRT, or PBT reported distinct patterns of treatment-related QOL. Although the timing of toxicity varied between the cohorts, patients reported similar modest QOL decrements in the bowel domain and minimal QOL decrements in the urinary domains at 24 months. Prospective randomized trials are needed to further examine these differences. PMID:23436283

  5. 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

  6. Monitoring the clinical outcomes in advanced prostate cancer: what imaging modalities and other markers are reliable?

    PubMed

    Morris, Michael J; Autio, Karen A; Basch, Ethan M; Danila, Daniel C; Larson, Steven; Scher, Howard I

    2013-06-01

    Effective patient care and efficient drug development require accurate tools to assess treatment effects. For metastatic castration-resistant prostate cancer (mCRPC), response biomarkers have historically been poorly reproducible, inaccurate, inconsistently applied, or only loosely associated with tangible clinical benefits such as survival. However, the field of response assessments for prostate cancer is maturing, in compliance with a rigorous process defined by analytic validation, clinical validation, and clinical qualification. For example, bone imaging with technetium-99m scintigraphy has historically been poorly used in prostate cancer clinical trials and routine patient care, and frequently has led to poor decision-making. However, contemporary clinical trial consensus criteria (Prostate Cancer Working Group 2 [PCWG2]) have standardized the definition of progression on bone scintigraphy and the clinical trials endpoint of radiographic progression-free survival (rPFS). A validated bone scan interpretation form captures the relevant data elements. rPFS and the forms have been undergoing prospective testing in multiple phase III studies. The first of these trials demonstrated a high degree of reproducibility and correlation with overall survival, and rPFS was used by the US Food and Drug Administration (FDA) for approval of abiraterone in chemotherapy-naïve mCRPC. Circulating tumor cells (CTC) are another class of assays with significant promise as response-indicator biomarkers. CTC enumeration has undergone analytic validation and has been FDA-cleared for monitoring patients with prostate cancer in conjunction with other clinical methods. It is not yet a surrogate for survival. Patient-reported outcomes (PROs) are direct indicators of patient benefit. The assays to measure PROs must undergo each of the steps of biomarker development, and are increasingly being standardized and used as clinical trial endpoints. In this review, we critically assess each of

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-Year Disease-Free Survival and Toxicity Observations

    PubMed Central

    Fuller, Donald Blake; Naitoh, John; Mardirossian, George

    2014-01-01

    Purpose: Prostate stereotactic body radiotherapy (SBRT) may substantially recapitulate the dose distribution of high-dose-rate (HDR) brachytherapy, representing an externally delivered “Virtual HDR” treatment method. Herein, we present 5-year outcomes from a cohort of consecutively treated virtual HDR SBRT prostate cancer patients. Methods: Seventy-nine patients were treated from 2006 to 2009, 40 low-risk, and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in four fractions. The planning target volume (PTV) included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered >95% of the PTV (V100 ≥95%), with a minimum 150% PTV dose escalation to create “HDR-like” PTV dose distribution. Results: Median pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70%) but only 3 of them subsequently relapsed, biochemical-relapse-free survival was 100 and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98 and 92% by Phoenix definition). Local relapse did not occur, distant metastasis-free survival was 100 and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10 and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0 and 1%, respectively, with no grade 3 or higher toxicity. Of patient’s potent pre-SBRT, 65% remained so at 5 years. Conclusion: Virtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported

  13. 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

  14. Tissue-type imaging (TTI) based on ultrasonic spectral and clinical parameters for detecting, evaluating, and managing prostate cancer

    NASA Astrophysics Data System (ADS)

    Feleppa, Ernest J.; Ketterling, Jeffrey A.; Dasgupta, Shreedevi; Kalisz, Andrew; Ramachandran, Sarayu; Porter, Christopher R.

    2005-04-01

    This study seeks to develop more-sensitive and -specific ultrasonic methods of imaging cancerous prostate tissue and thereby to improve means of guiding biopsies and planning, targeting, and monitoring treatment. Ultrasonic radio-frequency, echo-signal data, and clinical variables, e.g., PSA, voiding function, etc., during biopsy examinations were acquired. Spectra of the radio-frequency signals were computed in each biopsied region, and used to train neural networks; biopsy results served as the gold standard. A lookup table gave scores for cancer likelihood on a pixel-by-pixel basis from locally computed spectral-parameter and global clinical-parameter values. ROC curves used leave-one-patient- and leave-one-biopsy-out approaches to minimize classification bias. Resulting ROC-curve areas were 0.80+/-0.03 for neural-networks versus 0.66+/-0.03 for conventional classification. TTIs generated from data acquired pre-surgically showed tumors that were unrecognized in conventional images and during surgery. 3-D renderings of prostatectomy histology and TTIs showed encouraging correlations, which shows promise for improving the detection and management of prostate cancer, e.g., for biopsy guidance, planning dose-escalation and tissue-sparing options for radiation or cryotherapy, and assessing the effects of treatment. Combining MRS parameters with US spectral parameters appears capable of further improving prostate-cancer imaging. [Work supported by NIH.

  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. Pilot Study to Assess Safety and Clinical Outcomes of Irreversible Electroporation for Partial Gland Ablation in Men with Prostate Cancer

    PubMed Central

    Murray, Katie S.; Ehdaie, Behfar; Musser, John; Mashni, Joseph; Srimathveeravalli, Govindarajan; Durack, Jeremy C.; Solomon, Stephen B.; Coleman, Jonathan A.

    2016-01-01

    Purpose Partial prostate gland ablation is a strategy to manage localized prostate cancer. Irreversible electroporation can ablate localized soft tissues. We sought to describe 30- and 90-day complications and intermediate-term functional outcomes in men undergoing prostate gland ablation using irreversible electroporation. Materials and Methods We reviewed the charts of 25 patients with prostate cancer who underwent prostate gland ablation using irreversible electroporation as a primary procedure and who were followed for at least 6 months. Results Median follow-up was 10.9 months. Grade 3 complications occurred in 2 patients including epididymitis (1) and urinary tract infection (1). Fourteen patients experienced grade ≤ 2 complications, mainly transient urinary symptoms, hematuria, and urinary tract infections. Of 25 patients, 4 (16%) had cancer in the zone of ablation on routine follow-up biopsy at 6 months. Of those with normal urinary function at baseline, 88% and 94% reported normal urinary function at 6 and 12 months after prostate gland ablation, respectively. By 12 months, only 1 patient with normal erectile function at baseline reported new difficulty with potency and only 2 patients (8%) required a pad for urinary incontinence. Conclusions Prostate gland ablation with irreversible electroporation is feasible and safe in selected men with localized prostate cancer. Intermediate-term urinary and erectile function outcomes appear reasonable. Irreversible electroporation is effective in ablation of tumor-bearing prostate tissue, as a majority of men had no evidence of residual cancer on biopsy 6 months after prostate gland ablation. PMID:27113966

  17. Focal cryotherapy of localized prostate cancer: a systematic review of the literature.

    PubMed

    Shah, Taimur Tariq; Ahmed, Hashim; Kanthabalan, Abi; Lau, Benjamin; Ghei, Maneesh; Maraj, Barry; Arya, Manit

    2014-11-01

    Radical/whole gland treatment for prostate cancer has significant side-effects. Therefore focal treatments such as cryotherapy have been used to treat localized lesions whilst aiming to provide adequate cancer control with minimal side-effects. We performed a systematic review of Pubmed/Medline and Cochrane databases' to yield 9 papers for primary focal prostate cryotherapy and 2 papers for focal salvage treatment (radio-recurrent). The results of 1582 primary patients showed biochemical disease-free survival between 71-93% at 9-70 months follow-up. Incontinence rates were 0-3.6% and ED 0-42%. Recto-urethral fistula occurred in only 2 patients. Salvage focal cryotherapy had biochemical disease-free survival of 50-68% at 3 years. ED occurred in 60-71%. Focal cryotherapy appears to be an effective treatment for primary localized prostate cancer and compares favorably to radical/whole gland treatments in medium-term oncological outcomes and side-effects. Although more studies are needed it is also effective for radio-recurrent cancer with a low complications rates.

  18. 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.

  19. Design of clinical trials in advanced prostate cancer: avoiding the dead ends.

    PubMed

    Debruyne, Frans M J

    2005-12-01

    Despite more than 30 years of clinical trials, investigations in prostate cancer have not succeeded in making advances comparable to those in other branches of research, such as breast cancer. Indeed, prostate cancer trials have repeatedly run into a series of "dead ends", as investigators face the problems of inadequate funding for research, treatments that result in only minimal improvements in survival, and lack of treatment options that have sufficient prospects for success. This article briefly reviews the strategies behind clinical investigations into prostate cancer over the last three decades, evaluates the pitfalls that have hindered research, and makes suggestions for the appropriate design of clinical trials that are safe and beneficial to patients while maintaining cost-effectiveness and accountability to patients and society.

  20. Multiparametric MRI of prostate cancer: an update on state-of-the-art techniques and their performance in detecting and localizing prostate cancer.

    PubMed

    Hegde, John V; Mulkern, Robert V; Panych, Lawrence P; Fennessy, Fiona M; Fedorov, Andriy; Maier, Stephan E; Tempany, Clare M C

    2013-05-01

    Magnetic resonance (MR) examinations of men with prostate cancer are most commonly performed for detecting, characterizing, and staging the extent of disease to best determine diagnostic or treatment strategies, which range from biopsy guidance to active surveillance to radical prostatectomy. Given both the exam's importance to individual treatment plans and the time constraints present for its operation at most institutions, it is essential to perform the study effectively and efficiently. This article reviews the most commonly employed modern techniques for prostate cancer MR examinations, exploring the relevant signal characteristics from the different methods discussed and relating them to intrinsic prostate tissue properties. Also, a review of recent articles using these methods to enhance clinical interpretation and assess clinical performance is provided. J. Magn. Reson. Imaging 2013;37:1035-1054. © 2013 Wiley Periodicals, Inc.

  1. Multiparametric MRI of Prostate Cancer: An Update on State-of-the-Art Techniques and Their Performance in Detecting and Localizing Prostate Cancer

    PubMed Central

    Hegde, John V.; Mulkern, Robert V.; Panych, Lawrence P.; Fennessy, Fiona M.; Fedorov, Andriy; Maier, Stephan E.; Tempany, Clare M.C.

    2013-01-01

    Magnetic resonance (MR) examinations of men with prostate cancer are most commonly performed for detecting, characterizing, and staging the extent of disease to best determine diagnostic or treatment strategies, which range from biopsy guidance to active surveillance to radical prostatectomy. Given both the exam's importance to individual treatment plans and the time constraints present for its operation at most institutions, it is essential to perform the study effectively and efficiently. This article reviews the most commonly employed modern techniques for prostate cancer MR examinations, exploring the relevant signal characteristics from the different methods discussed and relating them to intrinsic prostate tissue properties. Also, a review of recent articles using these methods to enhance clinical interpretation and assess clinical performance is provided. PMID:23606141

  2. 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.

  3. Detection of sexually transmitted pathogens in patients with chronic prostatitis/chronic pelvic pain: a prospective clinical study.

    PubMed

    Papeš, Dino; Pasini, Miram; Jerončić, Ana; Vargović, Martina; Kotarski, Viktor; Markotić, Alemka; Škerk, Višnja

    2017-01-01

    In <10% of patients with prostatitis syndrome, a causative uropathogenic organism can be detected. It has been shown that certain organisms that cause sexually transmitted infections can also cause chronic bacterial prostatitis, which can be hard to diagnose and treat appropriately because prostatic samples obtained by prostatic massage are not routinely tested to detect them. We conducted a clinical study to determine the prevalence of Chlamydia, mycoplasma, and trichomonas infection in 254 patients that were previously diagnosed and treated for chronic prostatitis/chronic pelvic pain syndrome due to negative urethral swab, urine, and prostate samples. Urethral swabs and standard Meares-Stamey four-glass tests were done. Detailed microbiological analysis was conducted to detect the above organisms. Thirty-five (13.8%) patients had positive expressed prostatic secretions/VB3 samples, of which 22 (10.1%) were sexually transmitted organisms that were not detected on previous tests.

  4. Intense Uptake in Amyloidosis of the Seminal Vesicles on 68Ga-PSMA PET Mimicking Locally Advanced Prostate Cancer.

    PubMed

    Stephens, Maximilian; Kim, David Insoo; Shepherd, Benjamin; Gustafson, Sonja; Thomas, Paul

    2017-02-01

    We report a case of benign senile seminal vesicle amyloidosis demonstrating intense Ga-prostate-specific membrane antigen (PSMA) uptake on PET/CT. A 68-year-old man underwent staging PSMA PET/CT and MRI for biopsy-proven prostate adenocarcinoma. There was an intense focus of Ga-PSMA uptake in the primary malignancy, as well as symmetrical intense uptake in the seminal vesicles bilaterally that was reported as multifocal disease with local invasion. Final histology after radical prostatectomy showed amyloidosis of the seminal vesicles without any evidence of prostate cancer. Care should be taken in the interpretation of seminal vesicle PSMA uptake to avoid overstaging.

  5. A review of clinical effects associated with metabolic syndrome and exercise in prostate cancer patients

    PubMed Central

    Kiwata, J L; Dorff, T B; Schroeder, E T; Gross, M E; Dieli-Conwright, C M

    2016-01-01

    Androgen deprivation therapy (ADT), a primary treatment for locally advanced or metastatic prostate cancer, is associated with the adverse effects on numerous physiologic parameters, including alterations in cardiometabolic variables that overlap with components of the metabolic syndrome (MetS). As MetS is an established risk factor for cardiovascular mortality and treatment for prostate cancer has been associated with the development of MetS, interventions targeting cardiometabolic factors have been investigated in prostate cancer patients to attenuate the detrimental effects of ADT. Much support exists for exercise interventions in improving MetS variables in insulin-resistant adults, but less evidence is available in men with prostate cancer. Regular exercise, when performed at appropriate intensities and volumes, can elicit improvements in ADT-related adverse effects, including MetS, and contributes to the growing body of literature supporting the role of exercise in cancer survivorship. This review (1) discusses the biologic inter-relationship between prostate cancer, ADT and MetS, (2) evaluates the current literature in support of exercise in targeting MetS and (3) describes the physiological mechanisms by which exercise may favorably alter MetS risk factors in prostate cancer patients on ADT. PMID:27349496

  6. 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.

  7. Salvage brachytherapy in prostate local recurrence after radiation therapy: predicting factors for control and toxicity

    PubMed Central

    2014-01-01

    Purpose To evaluate efficacy and toxicity after salvage brachytherapy (BT) in prostate local recurrence after radiation therapy. Methods and materials Between 1993 and 2007, we retrospectively analyzed 56 consecutively patients (pts) undergoing salvage brachytherapy. After local biopsy-proven recurrence, pts received 145 Gy LDR-BT (37 pts, 66%) or HDR-BT (19 pts, 34%) in different dose levels according to biological equivalent doses (BED2 Gy). By the time of salvage BT, only 15 pts (27%) received ADT. Univariate and multivariate analyses were performed to identify predictors of biochemical control and toxicities. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were graded using Common Terminology Criteria for Adverse Events (CTCv3.0). Results Median follow-up after salvage BT was 48 months. The 5-year FFbF was 77%. HDR and LDR late grade 3 GU toxicities were observed in 21% and 24%. Late grade 3 GI toxicities were observed in 2% (HDR) and 2.7% (LDR). On univariate analysis, pre-salvage prostate-specific antigen (PSA) > 10 ng/ml (p = 0.004), interval to relapse after initial treatment < 24 months (p = 0.004) and salvage HDR-BT doses BED2 Gy level < 227 Gy (p = 0.012) were significant in predicting biochemical failure. On Cox multivariate analysis, pre-salvage PSA, and time to relapse were significant in predicting biochemical failure. HDR-BT BED2 Gy (α/β 1.5 Gy) levels ≥ 227 (p = 0.013), and ADT (p = 0.049) were significant in predicting grade ≥ 2 urinary toxicity. Conclusions Prostate BT is an effective salvage modality in some selected prostate local recurrence patients after radiation therapy. Even, we provide some potential predictors of biochemical control and toxicity for prostate salvage BT, further investigation is recommended. PMID:24885287

  8. Non-coding RNAs in Prostate Cancer: From Discovery to Clinical Applications.

    PubMed

    Ceder, Yvonne

    2016-01-01

    Prostate cancer is a heterogeneous disease for which the molecular mechanisms are still not fully elucidated. Prostate cancer research has traditionally focused on genomic and epigenetic alterations affecting the proteome, but over the last decade non-coding RNAs, especially microRNAs, have been recognized to play a key role in prostate cancer progression. A considerable number of individual microRNAs have been found to be deregulated in prostate cancer and their biological significance elucidated in functional studies. This review will delineate the current advances regarding the involvement of microRNAs and their targets in prostate cancer biology as well as their potential usage in the clinical management of the disease. The main focus will be on microRNAs contributing to initiation and progression of prostate cancer, including androgen signalling, cellular plasticity, stem cells biology and metastatic processes. To conclude, implications on potential future microRNA-based therapeutics based on the recent advances regarding the interplay between microRNAs and their targets are discussed.

  9. Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy

    PubMed Central

    TUMATI, VASU; MATHUR, SANJEEV; SONG, KWANG; HSIEH, JER-TSONG; ZHAO, DAWEN; TAKAHASHI, MASAYA; DOBIN, TIMOTHY; GANDEE, LEAH; SOLBERG, TIMOTHY D.; HABIB, AMYN A.; SAHA, DEBABRATA

    2013-01-01

    The purpose of this study was to develop an aggressive locally advanced orthotopic prostate cancer model for assessing high-dose image-guided radiation therapy combined with biological agents. For this study, we used a modified human prostate cancer (PCa) cell line, PC3, in which we knocked down a tumor suppressor protein, DAB2IP (PC3-KD). These prostate cancer cells were implanted into the prostate of nude or Copenhagen rats using either open surgical implantation or a minimally invasive procedure under ultrasound guidance. We report that: i) these DAB2IP-deficient PCa cells form a single focus of locally advanced aggressive tumors in both nude and Copenhagen rats; ii) the resulting tumors are highly aggressive and are poorly controlled after treatment with radiation alone; iii) ultrasound-guided tumor cell implantation can be used successfully for tumor development in the rat prostate; iv) precise measurement of the tumor volume and the treatment planning for radiation therapy can be obtained from ultrasound and MRI, respectively; and v) the use of a fiducial marker for enhanced radiotherapy localization in the rat orthotopic tumor. This model recapitulates radiation-resistant prostate cancers which can be used to demonstrate and quantify therapeutic response to combined modality treatments. PMID:23525451

  10. Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy.

    PubMed

    Tumati, Vasu; Mathur, Sanjeev; Song, Kwang; Hsieh, Jer-Tsong; Zhao, Dawen; Takahashi, Masaya; Dobin, Timothy; Gandee, Leah; Solberg, Timothy D; Habib, Amyn A; Saha, Debabrata

    2013-05-01

    The purpose of this study was to develop an aggressive locally advanced orthotopic prostate cancer model for assessing high-dose image-guided radiation therapy combined with biological agents. For this study, we used a modified human prostate cancer (PCa) cell line, PC3, in which we knocked down a tumor suppressor protein, DAB2IP (PC3‑KD). These prostate cancer cells were implanted into the prostate of nude or Copenhagen rats using either open surgical implantation or a minimally invasive procedure under ultrasound guidance. We report that: i) these DAB2IP-deficient PCa cells form a single focus of locally advanced aggressive tumors in both nude and Copenhagen rats; ii) the resulting tumors are highly aggressive and are poorly controlled after treatment with radiation alone; iii) ultrasound-guided tumor cell implantation can be used successfully for tumor development in the rat prostate; iv) precise measurement of the tumor volume and the treatment planning for radiation therapy can be obtained from ultrasound and MRI, respectively; and v) the use of a fiducial marker for enhanced radiotherapy localization in the rat orthotopic tumor. This model recapitulates radiation-resistant prostate cancers which can be used to demonstrate and quantify therapeutic response to combined modality treatments.

  11. Acceptability of Fitbit for physical activity tracking within clinical care among men with prostate cancer

    PubMed Central

    Rosenberg, Dori; Kadokura, Elyse A; Bouldin, Erin D; Miyawaki, Christina E; Higano, Celestia S.; Hartzler, Andrea L.

    2016-01-01

    Prior research has not examined the acceptability of commercially available fitness tracking devices in men with prostate cancer, many of whom are at risk for conditions that physical activity could alleviate. We conducted an exploratory 3-week field study to examine acceptability of the Fitbit Zip and attitudes towards integrating fitness tracking into clinical care among men with prostate cancer. Twenty-six men used the Fitbit Zip for a one-week baseline phase followed by a 2-week optional use phase and then completed in-depth interviews. Interview data was analyzed using inductive thematic analysis. Participants found the device comfortable and easy to wear. Barriers to use included health and technology difficulties. Participants expressed value in sharing Fitbit data with their health care team. Findings support the use of easy to use and simple fitness trackers among men with prostate cancer and there could be opportunities to integrate fitness tracker data into clinical care. PMID:28269902

  12. Acceptability of Fitbit for physical activity tracking within clinical care among men with prostate cancer.

    PubMed

    Rosenberg, Dori; Kadokura, Elyse A; Bouldin, Erin D; Miyawaki, Christina E; Higano, Celestia S; Hartzler, Andrea L

    2016-01-01

    Prior research has not examined the acceptability of commercially available fitness tracking devices in men with prostate cancer, many of whom are at risk for conditions that physical activity could alleviate. We conducted an exploratory 3-week field study to examine acceptability of the Fitbit Zip and attitudes towards integrating fitness tracking into clinical care among men with prostate cancer. Twenty-six men used the Fitbit Zip for a one-week baseline phase followed by a 2-week optional use phase and then completed in-depth interviews. Interview data was analyzed using inductive thematic analysis. Participants found the device comfortable and easy to wear. Barriers to use included health and technology difficulties. Participants expressed value in sharing Fitbit data with their health care team. Findings support the use of easy to use and simple fitness trackers among men with prostate cancer and there could be opportunities to integrate fitness tracker data into clinical care.

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

    PubMed Central

    Acosta, Oscar; Drean, Gael; Ospina, Juan David; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; De Crevoisier, Renaud

    2013-01-01

    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 80Gy to the prostate by IMRT. Within the patients presenting bleeding, a significant dose excess (6Gy on average, p<0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1cm), 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. PMID:23528429

  14. 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

  15. 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

  16. Mechanism of retention of estramustine in the rat prostate and results of a clinical trial of Estracyt in Japan

    SciTech Connect

    Yamanaka, H.; Imai, K.; Yuasa, H.; Shida, K.

    1981-01-01

    To clarify the mechanism of action of Estracyt, we performed experiments using /sup 3/H-estramustine of high specific activity. /sup 3/H-Radioactivity accumulated selectively in the ventral prostate of castrated male rats after the administration of /sup 3/H-estramustine. Estramustine and its metabolites were retained in the ventral prostate for long time periods. The uptake of /sup 3/H-radioactivity was almost totally localized in the cytosol fraction, but not in a purified receptor fraction. The apparent equilibrium dissociation constant of the estramustine binding protein was 18.9 nM, and the apparent equilibrium Bmax value was 0.76 nmoles/mg of cytosol protein. In addition, we wish to report in this paper the results of clinical trials of Estracyt studied by a cooperative research group in Japan from 1977 to 1979. It was concluded that Estracyt was effective in 89% of previously untreated prostatic cancer patients and in 38% of reactivated cancer patients.

  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. 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.

  19. Preoperative androgen deprivation therapy for localized prostate cancer: Delayed biochemical recurrence in high-risk disease

    PubMed Central

    Pal, Sumanta K.; Ruel, Nora; Voglezang, Nicholas; Chang, Mark; Wilson, Timothy G.; Jones, Jeremy O.; Yuh, Bertram

    2016-01-01

    Background The role of preoperative androgen deprivation therapy (ADT) for localized prostate cancer is controversial; prospective assessments have yielded varying results. We sought to define a subset of patients with a higher likelihood of benefit from preoperative ADT. Methods An institutional database including consecutive patients receiving definitive surgery for localized prostate cancer was interrogated. Patients recorded as having received preoperative ADT were matched in a 1:2 fashion to patients who had not received prior ADT. Patients were matched on the basis of clinicopathologic characteristics, use of adjuvant treatment strategies, and duration of PSA follow-up. Time to biochemical recurrence (TTBR) was compared using the Kaplan-Meier method and log-rank test for the overall study population and in subsets defined by D’Amico risk. Results No significant differences in clinicopathologic characteristics were noted between recipients (n=101) and matched non-recipients (n=196) of preoperative ADT. Although not statistically significant, positive surgical margin rates, seminal vesicle invasion and extracapsular extension were less frequent in patients receiving preoperative ADT. Furthermore, a lesser incidence of perioperative complications was noted in this group (7.4% v 18.4%). No significant differences were noted in TTBR between recipients and non-recipients of preoperative ADT in the overall study population. However, amongst patients with high-risk disease, TTBR was significantly longer in those patients who had received preoperative ADT (P=0.004). Conclusions The data presented herein suggest a potential benefit with preoperative ADT in patients with high-risk localized prostate cancer. Consideration should be given to enriching for this subset in preoperative studies of novel endocrine therapies. PMID:24342128

  20. 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

  1. 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.

  2. 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.

  3. The Clinical Development of Thalidomide as an Angiogenesis Inhibitor Therapy for Prostate Cancer

    DTIC Science & Technology

    2006-10-01

    AD_________________ Award Number: DAMD17-01-1-0069 TITLE: The Clinical Development of Thalidomide ...Development of Thalidomide as an Angiogenesis Inhibitor Therapy for Prostate Cancer 5b. GRANT NUMBER DAMD17-01-1-0069 5c. PROGRAM ELEMENT NUMBER 6...implicated in stromal epithelial interaction and have demonstrated that they are expressed in the context of Thalidomide treated patients. This

  4. 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.

  5. Perineural invasion is an independent predictor of biochemical recurrence of prostate cancer after local treatment: a meta-analysis.

    PubMed

    Meng, Yang; Liao, Yan-Biao; Xu, Peng; Wei, Wu-Ran; Wang, Jia

    2015-01-01

    Controversy still existed regarding the role of perineural invasion (PNI) in prostate cancer. The present meta-analysis aimed to investigate the association between PNI and biochemical recurrence (BCR) of prostate cancer after local treatment. A systematic search of Medline, Embase and CENTRAL was performed for eligible studies. Pooled estimates of hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were acquired by using the generic inverse variance method. Subgroup analyses were performed by the method treating prostate cancer including radical prostatectomy (RP) and radiotherapy (RT) as well as the specimens which were acquired from RP and biopsy. A total of 12 studies incorporating 5188 patients were included in the meta-analysis. Overall, PNI was significantly associated with BCR (HR 1.59, 95% CI 1.37-1.84). Similarly, a significant correlation between PNI and BCR was also found in RP series (HR 1.51, 95% CI 1.25-1.83) and RT series (HR 1.70, 95% CI 1.35-2.13). PNI predicted BCR of prostate cancer in both RP (HR 1.51, 95% CI 1.23-1.85) and biopsy specimens (HR 1.68, 95% CI 1.36-2.09). PNI was demonstrated to be associated with higher risk for BCR of prostate cancer after local treatment. Therefore, PNI should be considered when assessing the risk of BCR in prostate cancer, thereby to achieve the best treatment.

  6. [Options of hypofractionation of proton boost in locally advanced prostate cancer].

    PubMed

    Khmelevskiĭ, E V; Pan'shin, G A; Kancheli, I N; Khoroshkov, V S

    2012-01-01

    The aim was to evaluate the effectiveness of various fractionation proton boost in the proton-photon radiation therapy of locally advanced prostate cancer. The study included 272 patients with prostate cancer and intermediate-to-high risk of progression. 114 patients received 3-D conformal local irradiation of the prostate by proton beam 220Mev. The focal dose of 28-28,8 SoGy-eq was fed to the prostate for 8, 5 or 3 fractions for 3, 4 or 5.5 Gy-eq, respectively. Given the photon component (44 Gy in 22 fractions to the whole volume of the pelvis), the dose to the prostate was 72.8., 72 and 72SoGr-eq, respectively. In 158 patients in the control group the similar doses to the pelvis were supplemented by local 4-dipole photon irradiation of the prostate to 68-72 Gy in 12-14 fractions of 2 Gy. Acute gastro-intestinal (GI) toxicity maximum, 2 St expression, were found significantly less frequently after the proton-photon therapy: in 54.4% of cases, versus 69.2% in the controls (p <0,01). Differences between acute genito-urinary (GU) toxicity were not observed. The frequency of late GI damage of 2 St. was 3 times less frequently observed in the study group: 10.2% versus 34,8 +/-% in controls. Damages of 3-4 St. were found in 1 patient of the main group and in 2 patients in the control group. GU damages of 2 St. were equally common after the proton-photon or just photon irradiation in 8.3% and 9.1% of patients respectively. Damages of 3-4 St. were diagnosed in 2.8% and 3.8%, respectively (p> 0.05). A 5-year survival without biochemical recurrence was in the study and control groups 60,0 +/- 5,4% and 61,9 +/- 4,4%, and a 9-year survival--45,5 +/- 8,5% and 42,8 +/- 7 1%, respectively (p > 0.05). Thus, precise local irradiation by a proton beam with ROD 3-5.5 Gy-eq. and SOD 28-28,8 Gy-eq supplementing photon irradiation of total small pelvis significantly reduces the severity of early and late post-radiation proctitis but does not reduce the risk of damage to the lower

  7. Clinical Experience with (18)F-Labeled Small Molecule Inhibitors of Prostate-Specific Membrane Antigen.

    PubMed

    Rowe, Steven P; Gorin, Michael A; Salas Fragomeni, Roberto A; Drzezga, Alexander; Pomper, Martin G

    2017-04-01

    Prostate cancer (PCa) is the most common noncutaneous malignancy diagnosed in men. Despite the large number of men who will suffer from PCa at some point during their lives, conventional imaging modalities for this important disease (contrast-enhanced computed tomography, bone scan, and MR imaging) have provided only marginal to moderate success in appropriately guiding patient management in certain clinical contexts. In this review, the authors discuss radiofluorinated small molecule radiotracers that have been developed to bind to the transmembrane glycoprotein prostate-specific membrane antigen, a target that is nearly universally overexpressed on PCa epithelial cells.

  8. 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

  9. Locally-constrained Boundary Regression for Segmentation of Prostate and Rectum in the Planning CT Images

    PubMed Central

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

    2015-01-01

    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

  10. 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.

  11. Development and clinical introduction of automated radiotherapy treatment planning for prostate cancer

    NASA Astrophysics Data System (ADS)

    Winkel, D.; Bol, G. H.; van Asselen, B.; Hes, J.; Scholten, V.; Kerkmeijer, L. G. W.; Raaymakers, B. W.

    2016-12-01

    To develop an automated radiotherapy treatment planning and optimization workflow to efficiently create patient specifically optimized clinical grade treatment plans for prostate cancer and to implement it in clinical practice. A two-phased planning and optimization workflow was developed to automatically generate 77Gy 5-field simultaneously integrated boost intensity modulated radiation therapy (SIB-IMRT) plans for prostate cancer treatment. A retrospective planning study (n  =  100) was performed in which automatically and manually generated treatment plans were compared. A clinical pilot (n  =  21) was performed to investigate the usability of our method. Operator time for the planning process was reduced to  <5 min. The retrospective planning study showed that 98 plans met all clinical constraints. Significant improvements were made in the volume receiving 72Gy (V72Gy) for the bladder and rectum and the mean dose of the bladder and the body. A reduced plan variance was observed. During the clinical pilot 20 automatically generated plans met all constraints and 17 plans were selected for treatment. The automated radiotherapy treatment planning and optimization workflow is capable of efficiently generating patient specifically optimized and improved clinical grade plans. It has now been adopted as the current standard workflow in our clinic to generate treatment plans for prostate cancer.

  12. 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.

  13. 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

  14. 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

  15. Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic

    PubMed Central

    Morrison, Belinda F.; Aiken, William; Mayhew, Richard; Gordon, Yulit; Reid, Marvin

    2016-01-01

    Prostate cancer is highly prevalent in Jamaica and is the leading cause of cancer-related deaths. Our aim was to evaluate the patterns of screening in the largest organized screening clinic in Jamaica at the Jamaica Cancer Society. A retrospective analysis of all men presenting for screening at the Jamaica Cancer Society from 1995 to 2005 was done. All patients had digital rectal examinations (DRE) and prostate specific antigen (PSA) tests done. Results of prostate biopsies were noted. 1117 men of mean age 59.9 ± 8.2 years presented for screening. The median documented PSA was 1.6 ng/mL (maximum of 5170 ng/mL). Most patients presented for only 1 screen. There was a gradual reduction in the mean age of presentation for screening over the period. Prostate biopsies were requested on 11% of screening visits; however, only 59% of these were done. 5.6% of all persons screened were found to have cancer. Of the cancers diagnosed, Gleason 6 adenocarcinoma was the commonest grade and median PSA was 8.9 ng/mL (range 1.5–1059 ng/mL). Older men tend to screen for prostate cancer in Jamaica. However, compliance with regular maintenance visits and requests for confirmatory biopsies are poor. Screening needs intervention in the Jamaican population. PMID:27034668

  16. 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.

  17. 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

  18. 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.

  19. Decision aids for localized prostate cancer treatment choice: Systematic review and meta-analysis.

    PubMed

    Violette, Philippe D; Agoritsas, Thomas; Alexander, Paul; Riikonen, Jarno; Santti, Henrikki; Agarwal, Arnav; Bhatnagar, Neera; Dahm, Philipp; Montori, Victor; Guyatt, Gordon H; Tikkinen, Kari A O

    2015-01-01

    Patients who are diagnosed with localized prostate cancer need to make critical treatment decisions that are sensitive to their values and preferences. The role of decision aids in facilitating these decisions is unknown. The authors conducted a systematic review of randomized trials of decision aids for localized prostate cancer. Teams of 2 reviewers independently identified, selected, and abstracted data from 14 eligible trials (n = 3377 men), of which 10 were conducted in North America. Of these, 11 trials compared decision aids with usual care, and 3 trials compared decision aids with other decision aids. Two trials suggested a modest positive impact on decisional regret. Results across studies varied widely for decisional conflict (4 studies), satisfaction with decision (2 studies), and knowledge (2 studies). No impact on treatment choices was observed (6 studies). In conclusion, scant evidence at high risk of bias suggests the variable impact of existing decision aids on a limited set of decisional processes and outcomes. Because current decision aids provide information but do not directly facilitate shared decision making, subsequent efforts would benefit from user-centered design of decision aids that promote shared decision making.

  20. 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.

  1. Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

    DTIC Science & Technology

    2015-10-01

    Award Number: W81XWH-11-1-0639 TITLE: Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval PRINCIPAL...Clinical Trials and Drug Approval 5b. GRANT NUMBER PC100563 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Betty Diamond 5d. PROJECT NUMBER Ethan Basch...meet regulatory requirements for drug approval and labeling. The primary aim of this award is to conduct an observational longitudinal study in men

  2. Protons or megavoltage X-rays as boost therapy for patients irradiated for localized prostatic carcinoma. An early phase I/II comparison

    SciTech Connect

    Duttenhaver, J.R.; Shipley, W.U.; Perrone, T.; Verhey, L.J.; Goitein, M.; Munzenrider, J.E.; Prout, G.R.; Parkhurst, E.C.; Suit, H.D.

    1983-05-01

    A total of 180 patients with carcinoma of the prostate limited to the pelvis were treated with one of two external beam irradiation techniques between 1972 and 1979. One hundred and sixteen patients were treated with conventional pelvic megavoltage x-ray therapy. Sixty-four patients were treated with combined pelvic x-ray therapy plus a perineal proton beam boost to a carefully defined prostatic tumor volume. A 160 MeV proton beam has been modified to irradiate patients with localized tumors by using conventional treatment schedules. This proton beam has the physical advantage over megavoltage x-rays of reducing the dose to normal tissues adjacent to the tumor volume. By using the proton beam boost we have delivered an increased prostatic tumor dose of 500 to 700 cGy without increasing treatment morbidity at all. The two groups are actuarially analyzed for patient survival, disease-free survival and local recurrence-free survival, and thus far, no significant differences have been noted. Because of the minimal complications observed in the proton group despite a 10% increase in dose, a randomized clinical trial comparing these two treatment techniques is studied.

  3. 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.

  4. 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

  5. Information Needs of Men with Localized Prostate Cancer During Radiation Therapy.

    PubMed

    Wolpin, Seth E; Parks, Jason; Galligan, Mary; Russell, Kenneth J; Berry, Donna L

    2016-03-01

    The purpose of this study was to describe how patient information needs change over the course of receiving radiation therapy for prostate cancer. Convenience sampling was utilized to recruit men with stage I-III prostate cancer. A longitudinal repeated measures design was implemented for this pilot study. Patients were presented with 36 paired comparisons, each asking the participant to choose the most important information topic(s) for today. Following completion of the survey instruments, the clinic nurse delivered the four top-ranked information topic handouts to each patient with brief instruction on how to use the handouts. Over the course of 6 months, we were able to recruit 35 men. The four highest priority topics across all four sessions were prognosis, stage of disease, treatment options, and side effects. Our results suggest trends in the information priorities that men hold over the course of radiation treatment. The information priorities do appear to shift over time, notably prognosis concerns and risk for family members continued to rise over time, while side effect information declined. These findings will extend an already strong foundation of evidence for preparatory information in radiation therapy. Furthermore, these findings will strengthen current evidence that computerized assessment of patient self-report information is feasible and an important adjunct to clinical practice.

  6. Clinical significance of the prostate-specific antigen doubling time prior to and following radical prostatectomy to predict the outcome of prostate cancer

    PubMed Central

    Takeuchi, Hisashi; Ohori, Makoto; Tachibana, Masaaki

    2017-01-01

    With the advent of serum prostate-specific antigen (PSA), a larger number of prostate cancers in the early phase have been successfully detected. Although decisions to perform prostate biopsies are routinely based on PSA levels, the PSA level is easily influenced by benign prostatic hyperplasia, with poor specificity. Therefore, the aim of the present study was to assess the clinical significance of prostate-specific antigen doubling time (PSADT) prior to and following radical prostatectomy. In total, 488 patients with T1c-3N0M0 prostate cancer who underwent radical prostatectomy were included. Preoperative and postoperative PSADT were retrospectively correlated with pathological and clinical outcomes. Preoperative PSADT was measured in 204 of the 488 patients. In total, 16 out of 20 patients with a preoperative PSADT of >24 months had a cancer confined to the prostate compared with 105 of 184 patients with a PSADT of <24 months. The PSA non-recurrence rate at 5 years for patients with a preoperative PSADT of >24 months was significantly better compared with those with a preoperative PSADT of <24 months (P=0.011). Patients with a PSADT of >24 months and stable PSADT were associated with PSA recurrence following surgery, based on multivariate analysis. Postoperative PSADT was measured in 51 of 111 patients with PSA failure following surgery. Pathologically, 7 of 8 patients with a post-PSADT of >24 months had a cancer confined to the prostate compared with 14 of 43 patients with a post-PSADT of <24 months. These results suggest that patients with longer preoperative PSADTs appeared to have a favorable pathological result and a higher PSA non-recurrence rate compared with those with shorter preoperative PSADTs. A longer postoperative PSADT may facilitate the observation of patients with PSA recurrence without immediate secondary treatments. PMID:28357104

  7. High expression of PDGFR-β in prostate cancer stroma is independently associated with clinical and biochemical prostate cancer recurrence

    PubMed Central

    Nordby, Yngve; Richardsen, Elin; Rakaee, Mehrdad; Ness, Nora; Donnem, Tom; Patel, Hiten R. H.; Busund, Lill-Tove; Bremnes, Roy M.; Andersen, Sigve

    2017-01-01

    Due to a lack of sufficient diagnostic tools to predict aggressive disease, there is a significant overtreatment of patients with prostate cancer. Platelet derived growth factors (PDGFs) and their receptors (PDGFRs) are key regulators of mesenchymal cells in the tumor microenvironment, and has been associated with unfavorable outcome in several other cancers. Herein, we aimed to investigate the prognostic impact of PDGFR-β and its ligands (PDGF-B and PDGF-D) in a multicenter prostatectomy cohort of 535 Norwegian patients. Using tissue microarrays and immunohistochemistry, the expression of ligands PDGF-B and PDGF-D and their corresponding receptor, PDGFR-β, was assessed in neoplastic tissue and tumor-associated stroma. PDGFR-β was expressed in benign and tumor associated stroma, but not in epithelium. High stromal expression of PDGFR-β was independently associated with clinical relapse (HR = 2.17, p = 0.010) and biochemical failure (HR = 1.58, p = 0.002). This large study highlights the prognostic importance of PDGFR-β expression, implicating its involvement in prostate cancer progression even in early stage disease. Hence, analyses of PDGFR-β may help distinguish which patients will benefit from radical treatment, and since PDGFR-β is associated with relapse and shorter survival, it mandates a focus as a therapeutic target. PMID:28233816

  8. New frontiers in prostate cancer imaging: clinical utility of prostate-specific membrane antigen positron emission tomography.

    PubMed

    Afaq, Asim; Batura, Deepak; Bomanji, Jamshed

    2017-02-14

    Prostate-specific membrane antigen positron emission tomography (PSMA PET) is a relatively new method of imaging prostate cancer that increases diagnostic accuracy in detecting and guiding management in various stages of the disease pathway. Gallium-68-labelled PSMA PET has increased the sensitivity of detection of disease recurrence at low PSA levels, thus allowing an optimal window for salvage treatment. Apart from its use in disease recurrence, PSMA PET has the potential for increasing sensitivity and specificity for primary tumour localisation and in detecting lymph node disease, leading to a more accurate initial staging of the condition. In advanced disease, the use of PSMA PET may be able to assess response to treatment and also guide treatment with radionuclide therapy. Newer ligands under development might provide avenues for theranostic or personalised therapy applications with early data showing high PSA response rates. The rate of translation of PSMA PET into clinical practice has been remarkable. The use of this modality is likely to increase with future efforts to modify the radiotracer including (18)F labelling to improve availability.

  9. 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.

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

    PubMed

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

    2013-04-21

    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.

  11. 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.

  12. 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.

  13. Prostate cancer localization with multispectral MRI using cost-sensitive support vector machines and conditional random fields.

    PubMed

    Artan, Yusuf; Haider, Masoom A; Langer, Deanna L; van der Kwast, Theodorus H; Evans, Andrew J; Yang, Yongyi; Wernick, Miles N; Trachtenberg, John; Yetik, Imam Samil

    2010-09-01

    Prostate cancer is a leading cause of cancer death for men in the United States. Fortunately, the survival rate for early diagnosed patients is relatively high. Therefore, in vivo imaging plays an important role for the detection and treatment of the disease. Accurate prostate cancer localization with noninvasive imaging can be used to guide biopsy, radiotherapy, and surgery as well as to monitor disease progression. Magnetic resonance imaging (MRI) performed with an endorectal coil provides higher prostate cancer localization accuracy, when compared to transrectal ultrasound (TRUS). However, in general, a single type of MRI is not sufficient for reliable tumor localization. As an alternative, multispectral MRI, i.e., the use of multiple MRI-derived datasets, has emerged as a promising noninvasive imaging technique for the localization of prostate cancer; however almost all studies are with human readers. There is a significant inter and intraobserver variability for human readers, and it is substantially difficult for humans to analyze the large dataset of multispectral MRI. To solve these problems, this study presents an automated localization method using cost-sensitive support vector machines (SVMs) and shows that this method results in improved localization accuracy than classical SVM. Additionally, we develop a new segmentation method by combining conditional random fields (CRF) with a cost-sensitive framework and show that our method further improves cost-sensitive SVM results by incorporating spatial information. We test SVM, cost-sensitive SVM, and the proposed cost-sensitive CRF on multispectral MRI datasets acquired from 21 biopsy-confirmed cancer patients. Our results show that multispectral MRI helps to increase the accuracy of prostate cancer localization when compared to single MR images; and that using advanced methods such as cost-sensitive SVM as well as the proposed cost-sensitive CRF can boost the performance significantly when compared to SVM.

  14. [Prostate cancer].

    PubMed

    Bey, P; Beckendorf, V; Stinès, J

    2001-10-01

    Radiation therapy of prostate carcinoma with a curative intent implies to treat the whole prostate at high dose (at least 66 Gy). According to clinical stage, PSA level, Gleason's score, the clinical target volume may include seminal vesicles and less often pelvic lymph nodes. Microscopic extracapsular extension is found in 15 to 60% of T1-T2 operated on, specially in apex tumors. On contrary, cancers developing from the transitional zone may stay limited to the prostate even with a big volume and with a high PSA level. Zonal anatomy of the prostate identifies internal prostate, including the transitional zone (5% of the prostate in young people). External prostate includes central and peripheral zones. The inferior limit of the prostate is not lower than the inferior border of the pubic symphysis. Clinical and radiological examination: ultrasonography, nuclear magnetic resonance (NMR), CT-scan identify prognostic factors as tumor volume, capsule effraction, seminal vesicles invasion and lymph node extension. The identification of the clinical target volume is now done mainly by CT-Scan which identifies prostate and seminal vesicles. NMR could be helpful to identify more precisely prostate apex. The definition of margins around the clinical target volume has to take in account daily reproducibility and organ motion and of course the maximum tolerable dose for organs at risk.

  15. Xanthogranulomatous Prostatitis, a Rare Prostatic Entity.

    PubMed

    Noyola, Alejandro; Gil, José Fernando; Lujano, Heriberto; Piñon, Omar; Muñoz, Gabriel; Michel, José Manuel; Garcia, Jorge; Valdez, Jorge; Morales, Omar

    2017-01-01

    There are several benign prostatic pathologies that can clinically mimic a prostate adenocarcinoma. Xanthogranulomatous prostatitis is a benign inflammatory condition of the prostate and a rare entity. A 47-year old male, with 3 years of lower urinary tract symptoms, with a palpable hypogastric tumor, digital rectal examination: solid prostate, of approximately 60 g. Initial PSA was 0.90 ng/mL. He underwent surgical excision of the lower abdominal nodule and prostatectomy. Histopathology showed xanthogranulomatous prostatitis, without malignancy. Xanthogranulomatous prostatitis is an extremely rare entity that can simulate prostate adenocarcinoma, therefore having a correct histopathological diagnosis is essential.

  16. 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

  17. Intense Androgen-Deprivation Therapy With Abiraterone Acetate Plus Leuprolide Acetate in Patients With Localized High-Risk Prostate Cancer: Results of a Randomized Phase II Neoadjuvant Study

    PubMed Central

    Taplin, Mary-Ellen; Montgomery, Bruce; Logothetis, Christopher J.; Bubley, Glenn J.; Richie, Jerome P.; Dalkin, Bruce L.; Sanda, Martin G.; Davis, John W.; Loda, Massimo; True, Lawrence D.; Troncoso, Patricia; Ye, Huihui; Lis, Rosina T.; Marck, Brett T.; Matsumoto, Alvin M.; Balk, Steven P.; Mostaghel, Elahe A.; Penning, Trevor M.; Nelson, Peter S.; Xie, Wanling; Jiang, Zhenyang; Haqq, Christopher M.; Tamae, Daniel; Tran, NamPhuong; Peng, Weimin; Kheoh, Thian; Molina, Arturo; Kantoff, Philip W.

    2014-01-01

    Purpose Cure rates for localized high-risk prostate cancers (PCa) and some intermediate-risk PCa are frequently suboptimal with local therapy. Outcomes are improved by concomitant androgen-deprivation therapy (ADT) with radiation therapy, but not by concomitant ADT with surgery. Luteinizing hormone–releasing hormone agonist (LHRHa; leuprolide acetate) does not reduce serum androgens as effectively as abiraterone acetate (AA), a prodrug of abiraterone, a CYP17 inhibitor that lowers serum testosterone (< 1 ng/dL) and improves survival in metastatic PCa. The possibility that greater androgen suppression in patients with localized high-risk PCa will result in improved clinical outcomes makes paramount the reassessment of neoadjuvant ADT with more robust androgen suppression. Patients and Methods A neoadjuvant randomized phase II trial of LHRHa with AA was conducted in patients with localized high-risk PCa (N = 58). For the first 12 weeks, patients were randomly assigned to LHRHa versus LHRHa plus AA. After a research prostate biopsy, all patients received 12 additional weeks of LHRHa plus AA followed by prostatectomy. Results The levels of intraprostatic androgens from 12-week prostate biopsies, including the primary end point (dihydrotestosterone/testosterone), were significantly lower (dehydroepiandrosterone, Δ4-androstene-3,17-dione, dihydrotestosterone, all P < .001; testosterone, P < .05) with LHRHa plus AA compared with LHRHa alone. Prostatectomy pathologic staging demonstrated a low incidence of complete responses and minimal residual disease, with residual T3- or lymph node–positive disease in the majority. Conclusion LHRHa plus AA treatment suppresses tissue androgens more effectively than LHRHa alone. Intensive intratumoral androgen suppression with LHRHa plus AA before prostatectomy for localized high-risk PCa may reduce tumor burden. PMID:25311217

  18. Use of step-section histopathology to evaluate 18F-fluorocholine PET sextant localization of prostate cancer.

    PubMed

    Kwee, Sandi A; Thibault, Gregory P; Stack, Richard S; Coel, Marc N; Furusato, Bungo; Sesterhenn, Isabell A

    2008-01-01

    To assess positron emission tomography (PET) with fluorine-18 fluorocholine for sextant localization of malignant prostate tumors. Histopathologic analysis was performed on step-sectioned whole-mounted prostate specimens from 15 patients who underwent PET with fluorocholine prior to radical prostatectomy. The maximum standardized uptake value (SUVmax) corresponding to prostate sextants on PET was measured by region of interest analysis and compared with histopathologic results. Histopathology demonstrated malignant involvement in 61 of 90 prostate sextants. The mean total tumor volume per specimen was 4.9 mL (range 0.01-28.7 mL). Mean SUVmax was 6.0+/-2.0 in malignant sextants and 3.8+/-1.4 in benign sextants (p<.0001). The area under the receiver operating characteristic curve was 0.82 for sextant detection of malignancy based on SUVmax measurement. Tumor diameter directly correlated with sextant SUVmax in malignant sextants (r=.54, p<.05). In 13 subjects, the largest tumor in the specimen corresponded to the sextant with the highest SUVmax. Fluorocholine PET can serve to localize dominant areas of malignancy in patients with prostate cancer. However, PET with fluorocholine may fail to identify sextants with smaller volumes of malignancy.

  19. 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.

  20. 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

  1. 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.

  2. The T cell receptor gamma chain alternate reading frame protein (TARP), a prostate-specific protein localized in mitochondria.

    PubMed

    Maeda, Hiroshi; Nagata, Satoshi; Wolfgang, Curt D; Bratthauer, Gary L; Bera, Tapan K; Pastan, Ira

    2004-06-04

    We previously showed that mRNA encoding TARP (T cell receptor gamma chain alternate reading frame protein) is exclusively expressed in the prostate in males and is up-regulated by androgen in LNCaP cells, an androgen-sensitive prostate cancer cell line. We have now developed an anti-TARP monoclonal antibody named TP1, and show that TARP protein is up-regulated by androgen in both LNCaP and MDA-PCa-2b cells. We used TP1 to determine the subcellular localization of TARP by Western blotting following subcellular fractionation and immunocytochemistry. Both methods showed that TARP is localized in the mitochondria of LNCaP cells, MDA-PCa-2b cells, and PC-3 cells transfected with a TARP-expressing plasmid. We also transfected a plasmid encoding TARP fused to green fluorescent protein into LNCaP, MDA-Pca-2b, and PC-3 cells and confirmed its specific mitochondrial localization in living cells. Fractionation of mitochondria shows that TARP is located in the outer mitochondrial membrane. Immunohistochemistry using a human prostate cancer sample showed that TP1 reacted in a dot-like cytoplasmic pattern consistent with the presence of TARP in mitochondria. These data demonstrate that TARP is the first prostate-specific protein localizing in mitochondria and indicate that TARP, an androgen-regulated protein, may act on mitochondria to carry out its biological functions.

  3. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3

    PubMed Central

    Morris, Michael J.; Stadler, Walter M.; Higano, Celestia; Basch, Ethan; Fizazi, Karim; Antonarakis, Emmanuel S.; Beer, Tomasz M.; Carducci, Michael A.; Chi, Kim N.; Corn, Paul G.; de Bono, Johann S.; Dreicer, Robert; George, Daniel J.; Heath, Elisabeth I.; Hussain, Maha; Kelly, Wm. Kevin; Liu, Glenn; Logothetis, Christopher; Nanus, David; Stein, Mark N.; Rathkopf, Dana E.; Slovin, Susan F.; Ryan, Charles J.; Sartor, Oliver; Small, Eric J.; Smith, Matthew Raymond; Sternberg, Cora N.; Taplin, Mary-Ellen; Wilding, George; Nelson, Peter S.; Schwartz, Lawrence H.; Halabi, Susan; Kantoff, Philip W.; Armstrong, Andrew J.

    2016-01-01

    Purpose Evolving treatments, disease phenotypes, and biology, together with a changing drug development environment, have created the need to revise castration-resistant prostate cancer (CRPC) clinical trial recommendations to succeed those from prior Prostate Cancer Clinical Trials Working Groups. Methods An international expert committee of prostate cancer clinical investigators (the Prostate Cancer Clinical Trials Working Group 3 [PCWG3]) was reconvened and expanded and met in 2012-2015 to formulate updated criteria on the basis of emerging trial data and validation studies of the Prostate Cancer Clinical Trials Working Group 2 recommendations. Results PCWG3 recommends that baseline patient assessment include tumor histology, detailed records of prior systemic treatments and responses, and a detailed reporting of disease subtypes based on an anatomic pattern of metastatic spread. New recommendations for trial outcome measures include the time to event end point of symptomatic skeletal events, as well as time to first metastasis and time to progression for trials in the nonmetastatic CRPC state. PCWG3 introduces the concept of no longer clinically benefiting to underscore the distinction between first evidence of progression and the clinical need to terminate or change treatment, and the importance of documenting progression in existing lesions as distinct from the development of new lesions. Serial biologic profiling using tumor samples from biopsies, blood-based diagnostics, and/or imaging is also recommended to gain insight into mechanisms of resistance and to identify predictive biomarkers of sensitivity for use in prospective trials. Conclusion PCWG3 moves drug development closer to unmet needs in clinical practice by focusing on disease manifestations most likely to affect prognosis adversely for therapeutics tested in both nonmetastatic and metastatic CRPC populations. Consultation with regulatory authorities is recommended if a trial is intended to seek

  4. Germline genetic profiling in prostate cancer: latest developments and potential clinical applications

    PubMed Central

    Ahmed, Mahbubl; Eeles, Rosalind

    2016-01-01

    Familial and twin studies have demonstrated a significant inherited component to prostate cancer predisposition. Genome wide association studies have shown that there are 100 single nucleotide polymorphisms which have been associated with the development of prostate cancer. This review aims to discuss the scientific methods used to identify these susceptibility loci. It will also examine the current clinical utility of these loci, which include the development of risk models as well as predicting treatment efficacy and toxicity. In order to refine the clinical utility of the susceptibility loci, international consortia have been developed to combine statistical power as well as skills and knowledge to further develop models that could be used to predict risk and treatment outcomes. PMID:28031937

  5. 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

  6. Clinical and biological significance of CXCR5 expressed by prostate cancer specimens and cell lines.

    PubMed

    Singh, Shailesh; Singh, Rajesh; Singh, Udai P; Rai, Shesh N; Novakovic, Kristian R; Chung, Leland W K; Didier, Peter J; Grizzle, William E; Lillard, James W

    2009-11-15

    Chemokines and chemokine receptors have been shown to be involved in metastatic process of prostate cancer (PCa). In this study, we show primary PCa tissues and cell lines (LNCaP and PC3) express CXCR5, a specific chemokine receptor for CXCL13. Expression of CXCR5 was significantly higher (p < 0.001) in PCa cases than compared to normal match (NM) tissues. CXCR5 intensity correlated (R(2) = 0.97) with Gleason score. While prostate tumor tissues with Gleason scores >or= 7, displayed predominantly nuclear CXCR5 expression patterns, PCa specimens with Gleason scores prostatic hyperplasia (BPH). Similar to tissue expression, PCa cell lines expressed significantly more CXCR5 than normal prostatic epithelial cells (PrECs), and CXCR5 expression was distributed among intracellular and extracellular compartments. Functional in vitro assays showed higher migratory and invasive potentials toward CXCL13, an effect that was mediated by CXCR5. In both PCa cell lines, CXCL13 treatment increased the expression of collagenase-1 or matrix metalloproteinase-1 (MMP-1), collagenase-3 (MMP-13), stromelysin-1 (MMP-3), stromelysin-2 (MMP-10) and stromelysin-3 (MMP-11). These data demonstrate the clinical and biological relevance of the CXCL13-CXCR5 pathway and its role in PCa cell invasion and migration.

  7. 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.

  8. Stromal prostatic sarcoma: a rare tumor with rare clinical and imaging presentation

    PubMed Central

    Rojas-Jiménez, Anamaría; Otero-Garcia, Milagros; Mateos-Martin, Alejandro

    2013-01-01

    Adult prostatic stromal sarcoma is a rare malignant tumor. The main presenting symptom is urinary retention secondary to bladder outlet obstruction. Prostatic Specific Antigen level can be normal. Imaging features show a prostate mass with or without pelvic organ invasion depending on the aggressiveness of the tumor. We present a patient with prostatic stromal sarcoma who debuted with urinary obstruction, leukocytosis and neutrophilia, prostate enlargement, and hypodense prostate areas on CT images, simulating prostatitis with abscess formation. PMID:24421945

  9. Cancer control and complications of salvage local therapy after failure of radiotherapy for prostate cancer: a systematic review.

    PubMed

    Parekh, Arti; Graham, Powell L; Nguyen, Paul L

    2013-07-01

    The National Comprehensive Cancer Network guidelines currently endorse salvage local therapy as a reasonable alternative to observation or androgen-deprivation therapy for select men with a biopsy-proven local recurrence after definitive radiation for prostate cancer. Patients being considered for salvage therapy should have had localized disease at presentation, a prostate-specific antigen < 10 at recurrence, a life expectancy >10 years at recurrence, and a negative metastatic workup. In this systematic review, we synthesize the current literature describing the oncologic efficacy and toxicity profile of salvage brachytherapy, prostatectomy, cryotherapy, and high-intensity focused ultrasound. We found 5-year biochemical control rates to be similar across treatments, in the range of 52%-56%, although patient selection and definition of failure was variable. Toxicity profiles were also distinct between local salvage modalities.

  10. 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.

  11. [Bacterial prostatitis and prostatic fibrosis: modern view on the treatment and prophylaxis].

    PubMed

    Zaitsev, A V; Pushkar, D Yu; Khodyreva, L A; Dudareva, A A

    2016-08-01

    Treatments of chronic bacterial prostatitis (CP) remain difficult problem. Bacterial prostatitis is a disease entity diagnosed clinically and by evidence of inflammation and infection localized to the prostate. Risk factors for UTI in men include urological interventions, such as transrectal prostate biopsy. Ensuing infections after prostate biopsy, such as UTI and bacterial prostatitis, are increasing due to increasing rates of fluoroquinolone resistance. The increasing global antibiotic resistance also significantly affects management of UTI in men, and therefore calls for alternative strategies. Prostatic inflammation has been suggested to contribute to the etiology of lower urinary tract symptoms (LUTS) by inducing fibrosis. Several studies have shown that prostatic fibrosis is strongly associated with impaired urethral function and LUTS severity. Fibrosis resulting from excessive deposition of collagen is traditionally recognized as a progressive irreversible condition and an end stage of inflammatory diseases; however, there is compelling evidence in both animal and human studies to support that the development of fibrosis could potentially be a reversible process. Prostate inflammation may induce fibrotic changes in periurethral prostatic tissues, promote urethral stiffness and LUTS. Patients experiencing CP and prostate-related LUTS could benefit from anti-inflammatory therapies, especially used in combination with the currently prescribed enzyme treatment with Longidase. Treatment results showed that longidase is highly effective in bacterial and abacterial CP. Longidase addition to standard therapeutic methods significantly reduced the disease symptoms and regression of inflammatory-proliferative alterations in the prostate.

  12. Long Term Progression-Free Survival in a Patient with Locally Advanced Prostate Cancer under Low Dose Intermittent Androgen Deprivation Therapy with Bicalutamide Only.

    PubMed

    Latz, Stefan; Fisang, Christian; Ebert, Wolfram; Orth, Stefan; Engehausen, Dirk G; Müller, Stefan C; Anding, Ralf

    2015-01-01

    Androgen deprivation is a common treatment option in patients with locally advanced or metastatic prostate cancer. No case of long term treatment with an intermittent approach with only low dose bicalutamide (50 mg daily) has been described yet. We report a 60-year-old patient, initially presenting with a PSA elevation of 19.2 ng/mL in 1996. After diagnosis of well to moderately differentiated prostate cancer by transrectal biopsy, the patient underwent an open radical prostatectomy. Final diagnosis was adenocarcinoma of the prostate, classified as pT3a, pR1, pV0, and pL1. Adjuvant intermittent androgen deprivation therapy with flutamide 250 mg was applied, which was changed to bicalutamide 50 mg once daily when it became available in 2001. Six on-phases were performed and PSA values never exceeded 20 ng/mL. The patient did not experience any serious side effects. To date, there are no clinical or radiological signs of progression. Current PSA value is 3.5 ng/mL.

  13. 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.

  14. The Clinical Development of Thalildomide as an Angiogenesis Inhibitor Therapy for Prostate Cancer

    DTIC Science & Technology

    2005-10-01

    AD_________________ Award Number: DAMD17-01-1-0069 TITLE: The Clinical Development of Thalidomide ... Thalidomide as an Angiogenesis Inhibitor Therapy for Prostate Cancer 5b. GRANT NUMBER DAMD17-01-1-0069 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...in stromal epithelial interaction and have demonstrated that they are expressed in the context of Thalidomide treated patients. This information will

  15. 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.

  16. Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer.

    PubMed

    Kovtun, Irina V; Murphy, Stephen J; Johnson, Sarah H; Cheville, John C; Vasmatzis, George

    2015-10-06

    Massive genomic rearrangements, a result of single catastrophic event termed chromothrispsis or chromosomal catastrophe, have been identified in a variety of human cancers. In a few cancer types, chromothripsis was found to be associated with poor prognosis. We performed mate-pair sequencing and analysis of structural rearrangements in 132 prostate cancer cases which included clinically insignificant Gleason score 6 tumors, clinically significant tumors of higher grade (7+) and high grade prostatic intraepithelial neoplasia. Chromothripsis was observed at least 30 per cent of the samples across different grades. Surprisingly, it was frequently observed in clinically insignificant Gleason score 6 tumors, indicating that chromothripsis does not define more aggressive phenotype. The degree of chromothripsis did not increase significantly in tumors of advanced grades and did not appear to contribute to tumor progression. Our data showed that distribution of chromothriptic rearrangements differed from that of fragile sites but correlated with the size of chromosomes. We also provided evidence that rearrangements resulting from chromothripsis were present in the cells of neighboring Gleason patterns of the same tumor. Our data suggest that that chromothripsis plays role in prostate cancer initiation.

  17. Development of a hypermedia program designed to assist patients with localized prostate cancer in making treatment decisions.

    PubMed

    Jenkinson, J; Wilson-Pauwels, L; Jewett, M A; Woolridge, N

    1998-01-01

    The Prostate Centre, a hypermedia program integrating CD-ROM and Internet technology, was developed to help patients with localized prostate cancer access detailed and current information about available treatment options. Personal interviews with ten patients confirmed the need for more specific information examining the diagnosis and treatment of prostate cancer, as well as the suitability of computers for conveying this information. Sample screen designs effectively determined patients' visual preferences and were a useful springboard for conversation about a number of other relevant topics. Pilot testing of the resulting prototype elicited a positive response about the program from this sample audience. Patients regarded the program as useful, relevant to their needs, and navigable. Although the small sample size limited the study's generalizability, the method of involving patients in the design process successfully guided the program's development toward a greater fit with the users' needs.

  18. 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.

  19. 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.

  20. Co-occurring gland angularity in localized subgraphs: predicting biochemical recurrence in intermediate-risk prostate cancer patients.

    PubMed

    Lee, George; Sparks, Rachel; Ali, Sahirzeeshan; Shih, Natalie N C; Feldman, Michael D; Spangler, Elaine; Rebbeck, Timothy; Tomaszewski, John E; Madabhushi, Anant

    2014-01-01

    Quantitative histomorphometry (QH) refers to the application of advanced computational image analysis to reproducibly describe disease appearance on digitized histopathology images. QH thus could serve as an important complementary tool for pathologists in interrogating and interpreting cancer morphology and malignancy. In the US, annually, over 60,000 prostate cancer patients undergo radical prostatectomy treatment. Around 10,000 of these men experience biochemical recurrence within 5 years of surgery, a marker for local or distant disease recurrence. The ability to predict the risk of biochemical recurrence soon after surgery could allow for adjuvant therapies to be prescribed as necessary to improve long term treatment outcomes. The underlying hypothesis with our approach, co-occurring gland angularity (CGA), is that in benign or less aggressive prostate cancer, gland orientations within local neighborhoods are similar to each other but are more chaotically arranged in aggressive disease. By modeling the extent of the disorder, we can differentiate surgically removed prostate tissue sections from (a) benign and malignant regions and (b) more and less aggressive prostate cancer. For a cohort of 40 intermediate-risk (mostly Gleason sum 7) surgically cured prostate cancer patients where half suffered biochemical recurrence, the CGA features were able to predict biochemical recurrence with 73% accuracy. Additionally, for 80 regions of interest chosen from the 40 studies, corresponding to both normal and cancerous cases, the CGA features yielded a 99% accuracy. CGAs were shown to be statistically signicantly ([Formula: see text]) better at predicting BCR compared to state-of-the-art QH methods and postoperative prostate cancer nomograms.

  1. The modern role of androgen deprivation therapy in the management of localised and locally advanced prostate cancer

    PubMed Central

    Gunner, Charlotte; Gulamhusein, Aziz; Rosario, Derek J

    2016-01-01

    Introduction: Approximately 50% of men diagnosed with prostate cancer will be exposed to androgen deprivation therapy (ADT) at some stage. The role of ADT in the management of metastatic disease has long been recognised, and its place in the management of localised and locally advanced disease has become clearer in the past few years. Nevertheless, concerns remain that some men might not benefit from ADT in earlier-stage disease. The purpose of the current article is to provide a brief narrative review of the role of ADT as part of a strategy of treatment with curative intent, concentrating mainly on key recent developments in the area. Methods: Narrative literature review of key publications in the English language relating to ADT in the management of localised and locally advanced prostate cancer. Results: In locally advanced and high-risk localised prostate cancer, the use of ADT in combination with radiotherapy improves disease-specific and overall survival. There is no evidence to support the use of ADT in the treatment of low-risk localised prostate cancer. There appears to be an increased risk of cardiovascular morbidity and mortality associated with luteinizing hormone-releasing hormone agonists, particularly in men with pre-existing cardiovascular disease, but the relevance of this in the adjuvant/neoadjuvant setting is currently unclear. Conclusions: Future studies should focus on identification of men who are at risk from cardiovascular complications associated with ADT and on the comparison of radiotherapy with ADT versus surgery in the management of localised and locally advanced prostate cancer, particularly with regards to men with pre-existing comorbidities.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. Role of ProstaScint for brachytherapy in localized prostate adenocarcinoma.

    PubMed

    Ellis, Rodney J; Kim, Edward; Foor, Ryan

    2004-07-01

    ProstaScint (CYT-356 or capromab pendetide, Cytogen) is an 111In-labeled monoclonal mouse antibody specific for prostate-specific membrane antigen, a prostate transmembrane glycoprotein that is upregulated in prostate adenocarcinoma. ProstaScint scans are US Food and Drug Administration approved for pretreatment evaluation of metastatic disease in high-risk patients. They are also approved for post-prostatectomy assessment of recurrent disease in patients with a rising prostate-specific antigen level. This review explores the literature on ProstaScint and its use in guiding the treatment of prostate cancer. A novel technique for identifying areas of cancer within the prostate using ProstaScint images fused with pelvic computed tomography scans is also described. The identification of areas of high antibody signal provides targets for radiotherapeutic dose escalation, with the overall goals of improving treatment outcome while preserving adjacent tissue structures and decreasing treatment morbidity.

  7. 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.

  8. Automatic segmentation of the prostate in 3D MR images by atlas matching using localized mutual information.

    PubMed

    Klein, Stefan; van der Heide, Uulke A; Lips, Irene M; van Vulpen, Marco; Staring, Marius; Pluim, Josien P W

    2008-04-01

    An automatic method for delineating the prostate (including the seminal vesicles) in three-dimensional magnetic resonance scans is presented. The method is based on nonrigid registration of a set of prelabeled atlas images. Each atlas image is nonrigidly registered with the target patient image. Subsequently, the deformed atlas label images are fused to yield a single segmentation of the patient image. The proposed method is evaluated on 50 clinical scans, which were manually segmented by three experts. The Dice similarity coefficient (DSC) is used to quantify the overlap between the automatic and manual segmentations. We investigate the impact of several factors on the performance of the segmentation method. For the registration, two similarity measures are compared: Mutual information and a localized version of mutual information. The latter turns out to be superior (median DeltaDSC approximately equal 0.02, p < 0.01 with a paired two-sided Wilcoxon test) and comes at no added computational cost, thanks to the use of a novel stochastic optimization scheme. For the atlas fusion step we consider a majority voting rule and the "simultaneous truth and performance level estimation" algorithm, both with and without a preceding atlas selection stage. The differences between the various fusion methods appear to be small and mostly not statistically significant (p > 0.05). To assess the influence of the atlas composition, two atlas sets are compared. The first set consists of 38 scans of healthy volunteers. The second set is constructed by a leave-one-out approach using the 50 clinical scans that are used for evaluation. The second atlas set gives substantially better performance (DeltaDSC=0.04, p < 0.01), stressing the importance of a careful atlas definition. With the best settings, a median DSC of around 0.85 is achieved, which is close to the median interobserver DSC of 0.87. The segmentation quality is especially good at the prostate-rectum interface, where the

  9. Information Seeking and Satisfaction with Information Sources Among Spouses of Men with Newly Diagnosed Local-Stage Prostate Cancer.

    PubMed

    Bansal, Aasthaa; Koepl, Lisel M; Fedorenko, Catherine R; Li, Chunyu; Smith, Judith Lee; Hall, Ingrid J; Penson, David F; Ramsey, Scott D

    2017-02-25

    Information sources about prostate cancer treatment and outcomes are typically designed for patients. Little is known about the availability and utility of information for partners. The objectives of our study were to evaluate information sources used by partners to understand prostate cancer management options, their perceived usefulness, and the relationship between sources used and satisfaction with treatment experience. A longitudinal survey of female partners of men newly diagnosed with local-stage prostate cancer was conducted in three different geographic regions. Partners and associated patients were surveyed at baseline (after patient diagnosis but prior to receiving therapy) and at 12 months following diagnosis. Information sources included provider, literature, friends or family members, Internet websites, books, traditional media, and support groups. Utility of an information source was defined as whether the partner would recommend it to caregivers of other patients with local-stage prostate cancer. Our study cohort included 179 partner-patient pairs. At diagnosis, partners consulted an average of 4.6 information sources. Non-Hispanic white partners were more likely than others to use friends and family as an information source (OR = 2.44, 95% CI (1.04, 5.56)). More educated partners were less likely to use support groups (OR = 0.31, 95% CI (0.14, 0.71)). At 12-month follow-up, partners were less likely to recommend books (OR = 0.23, 95% CI (0.11, 0.49)) compared to baseline. Partners consulted a large number of information sources in researching treatment options for local-stage prostate cancer and the types of sources accessed varied by race/ethnicity and educational attainment. Additional resources to promote selection of high-quality non-provider information sources are warranted to enable partners to better aid patients in their treatment decision-making process.

  10. Clinically Enhancing Local Anesthesia Techniques for Endodontic Treatment.

    PubMed

    Bahcall, James; Xie, Qian

    2017-02-01

    Local anesthesia is one of the most important drugs given to patients who undergo endodontic treatment. Yet, clinicians often do not view local anesthetic agents as drugs and, therefore, struggle clinically to consistently achieve profound pulpal anesthesia. To improve the clinical effects of local anesthesia for endodontic treatment, in conjunction with selecting the correct type of local anesthesia, clinicians need to thoroughly understand how the local anesthetic process works and how to objectively test for clinical signs of pulpal anesthesia and integrate supplemental anesthesia when appropriate.

  11. Prospective evaluation of quality of life 54 months after high-dose intensity-modulated radiotherapy for localized prostate cancer

    PubMed Central

    2013-01-01

    Objective To determine late toxicity and quality of life (QoL) in patients with localized prostate cancer after high-dose intensity-modulated radiotherapy (IMRT). Patient and methods This was a prospective study in patients with localized prostate adenocarcinoma who had been treated by IMRT (76 Gy) between February and November 2006. Physicians scored acute and late toxicity using the Common Terminology Criteria for Adverse Events (version 3.0). Patients completed cancer and prostate-specific QoL questionnaires (EORTC QLQ-C30 and QLQ-PR25) before IMRT (baseline) and at 2, 6, 18 and 54 months. Result Data were available for 38 patients (median age, 73 years) (18% low risk; 60% intermediate risk; 32% high risk). The incidence of urinary and gastrointestinal toxicity was respectively: immediately post IMRT: 36.8% and 23.7% (grade 1), 5.3% and 5.3% (grade 2), 2.6% and 0% (grade 3); at 18 months: 23.7% and 10.3% (grade 1), 26.3% and 13.2% (grade 2), 0% and 2.6% (grade 3); at 54 months: 34.2% and 23.7% (grade 1), 5.3% and 15.8% (grade 2), 5.3% and 0% (grade 3). At 54 months, significant worsening was reported by patients for 11/19 QoL items but the worsening was clinically relevant (>10 points) for 7 items only: physical, role as well as social functioning, fatigue, pain, dyspnoea and constipation. There was no significant difference between 54-month and baseline QoL scores for global health, gastrointestinal symptoms, treatment-related symptoms and sexual function. However, there was significant - but clinically non-relevant (<10 points) - worsening of urinary symptom. Conclusion High-dose IMRT to the prostate with accurate patient positioning did not induce any clinically relevant worsening in late urinary and gastrointestinal QoL at 54 months. Impaired physical and role functioning may be related to age and comorbidities. PMID:23510499

  12. Acute toxicity during external-beam radiotherapy for localized prostate cancer: Comparison of different techniques

    SciTech Connect

    Vijayakumar, S.; Awan, A.; Karrison, T.; Culbert, H.; Chan, S.; Kolker, J.; Low, N.; Halpern, H.; Rubin, S.; Chen, G.T.Y.; Weicheselbaum, R.R. )

    1993-01-15

    The chronic and acute toxicities associated with conventional radiotherapy of localized prostate cancer are well documented. However, the degree and incidence of toxicities with conformal techniques are not known. Studying side effects associated with modern radiotherapeutic techniques is more important now since there has been a general trend to use computerized tomography-based techniques in recent years; beam's eye view-based conformal techniques are also becoming more commonplace. It is possible that the local disease control can be improved with the delivery of higher doses than currently used. Conformation of the treatment volume to the target volume may facilitate such dose-escalation. However, prior to such dose-escalation, it is important to know the toxicities associated with such techniques with conventional doses. We have compared week-by-week acute toxicities associated with conventional (Group A, 16 patients), computerized tomography-based, manual (Group B, 57 patients) and beam's eye view-based (Group C, 43 patients) techniques during 7 weeks of radiotherapy. Group B and C patients were treated contemporaneously (1988-1990). The incidence of acute toxicities was significantly less with the beams eye view-based technique than with the other two methods. A trend suggesting increased severity of toxicity with increase in the volume of treatment was seen.

  13. 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.

  14. An Eight-Year Experience of HDR Brachytherapy Boost for Localized Prostate Cancer: Biopsy and PSA Outcome

    SciTech Connect

    Bachand, Francois; Martin, Andre-Guy; Beaulieu, Luc; Harel, Francois M.Sc.; Vigneault, Eric

    2009-03-01

    Purpose: To evaluate the biochemical recurrence-free survival (bRFS), the 2-year biopsy outcome and the prostate-specific antigen (PSA) bounce in patients with localized prostate cancer treated with an inversely planned high-dose-rate (HDR) brachytherapy boost. Materials and methods: Data were collected from 153 patients treated between 1999 and 2006 with external beam pelvic radiation followed by an HDR Ir-192 prostate boost. These patients were given a boost of 18 to 20 Gy using inverse-planning with simulated annealing (IPSA).We reviewed and analyzed all prostate-specific antigen levels and control biopsies. Results: The median follow-up was 44 months (18-95 months). When categorized by risk of progression, 74.5% of patients presented an intermediate risk and 14.4% a high one. Prostate biopsies at 2 years posttreatment were negative in 86 of 94 patients (91.5%), whereas two biopsies were inconclusive. Biochemical control at 60 months was at 96% according to the American Society for Therapeutic Radiology and Oncology and the Phoenix consensus definitions. A PSA bounce (PSA values of 2 ng/mL or more above nadir) was observed in 15 patients of 123 (9.8%). The median time to bounce was 15.2 months (interquartile range, 11.0-17.7) and the median bounce duration 18.7 months (interquartile range, 12.1-29). The estimate of overall survival at 60 months was 97.1% (95% CI, 91.6-103%). Conclusions: Considering that inverse planned HDR brachytherapy prostate boosts led to an excellent biochemical response, with a 2-year negative biopsy rate, we recommend a conservative approach in face of a PSA bounce even though it was observed in 10% of patients.

  15. 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

  16. Clinical study on the application of a 2-μm continuous wave laser in transurethral vaporesection of the prostate

    PubMed Central

    XU, YONG; SUN, DONGCHONG; WEI, ZHITAO; HONG, BAOFA; YANG, YONG

    2013-01-01

    The present study aimed to evaluate the method and clinical effects of transurethral dividing vaporesection of the prostate in the management of benign prostatic hyperplasia (BPH) using the RevoIix 70 W 2-μm continuous wave (cw) laser. A total of 155 BPH patients were treated transurethrally under epidural or sacral anesthesia using the dividing vaporesection technique. Of these, 80 had a prostate volume of ≤80 ml and 75 had a prostate volume of >80 ml. Pre- and post-operative data were evaluated for prostate-specific antigens (PSAs), post-void residual volume (PVR), maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS) and quality of life (QoL). Statistical analyses were performed using the SPSS 16.0 software. Treatment effectiveness evaluations were also conducted. In the ≤80 ml prostate volume group, the mean PSA level decreased from 3.8±0.9 to 2.6±1.3 ng/ml. The PVR, mean Qmax, IPSS and QoL score improved significantly (P<0.05) in each group but no statistically significant difference was identified between the two groups. With a shorter surgery duration, safe use and high cutting efficiency and rapid vaporization ability, the 2-μm laser vaporesection technique shows superiority compared to standard techniques in the treatment of BPH. PMID:23596476

  17. Prostatic aspergillosis.

    PubMed

    Abbas, F; Kamal, M K; Talati, J

    1995-03-01

    Prostatic aspergillosis is rare with only 3 cases reported previously. We report a case of localized invasive aspergillosis of the prostate in a nonimmunocompromised patient with chronic urinary retention and recurrent urinary tract infections. Transurethral resection followed by open prostatectomy was performed for massive prostatomegaly. No systemic antifungal therapy was required for cure. The literature is reviewed, and diagnostic and management options are discussed.

  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. 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.

  20. Patterns of Care, Utilization, and Outcomes of Treatments for Localized Prostate Cancer

    DTIC Science & Technology

    2011-05-01

    ORP), external beam radiotherapy (XRT), and brachytherapy (BRCY). The findings of this project will guide men with prostate cancer weighing... radiotherapy was administered. This study reinforces the importance of limiting positive surgical margins, which increase the cost of treating prostate...the study cohort, 26% received surgery, 38% external bean radiotherapy , and 36% brachytherapy.   10   Among surgical patients, MIRP utilization

  1. 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

  2. Prostate-specific antigen kinetics after stereotactic body radiotherapy as monotherapy or boost after whole pelvic radiotherapy for localized prostate cancer

    PubMed Central

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

    2015-01-01

    Purpose Stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. However, prostate-specific antigen (PSA) kinetics after SBRT has not been well characterized. The purpose of the current study is to assess the kinetics of PSA for low- and intermediate-risk prostate cancer patients treated with SBRT using Cyberknife as both monotherapy and boost after whole pelvic radiotherapy (WPRT) in the absence of androgen deprivation therapy. Methods A total of 61 patients with low- and intermediated-risk prostate cancer treated with SBRT as monotherapy (36.25 Gy in 5 fractions in 32 patients) and SBRT (21 Gy in 3 fractions in 29 patients) boost combined with WPRT (45 Gy in 25 fractions). Patients were excluded if they failed therapy by the Phoenix definition or had androgen deprivation therapy. PSA nadir and rate of change in PSA over time (slope) were calculated and compared. Results With a median follow-up of 52.4 months (range, 14–74 months), for SBRT monotherapy, the median PSA nadir was 0.31 ng/mL (range, 0.04–1.15 ng/mL) and slopes were –0.41 ng/mL/mo, –0.17 ng/mL/mo, –0.12 ng/mL/mo, and –0.09 ng/mL/mo, respectively, for durations of 1 year, 2 years, 3 years, and 4 years postradiotherapy. Similarly, for SBRT boost after WPRT, the median PSA nadir was 0.34 ng/mL (range, 0.04–1.44 ng/mL) and slopes were –0.53 ng/mL/mo, –0.25 ng/mL/mo, –0.14 ng/mL/mo, and –0.09 ng/mL/mo, respectively. The median nadir and slopes of SBRT monotherapy did not differ significantly from those of SBRT boost after WPRT. Benign PSA bounces were common in 30.4% of all cohorts, and the median time to PSA bounce was 12 months (range, 6–25 months). Conclusions In this report of low- and intermediate-risk prostate cancer patients, an initial period of rapid PSA decline was followed by a slow decline, which resulted in a lower PSA nadir. The PSA kinetics of SBRT monotherapy appears to be comparable to those achieved

  3. Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer

    PubMed Central

    Attard, G; Clark, J; Ambroisine, L; Mills, I G; Fisher, G; Flohr, P; Reid, A; Edwards, S; Kovacs, G; Berney, D; Foster, C; Massie, C E; Fletcher, A; De Bono, J S; Scardino, P; Cuzick, J; Cooper, C S

    2008-01-01

    A fluorescence in situ hybridisation (FISH) assay has been used to screen for ETV1 gene rearrangements in a cohort of 429 prostate cancers from patients who had been diagnosed by trans-urethral resection of the prostate. The presence of ETV1 gene alterations (found in 23 cases, 5.4%) was correlated with higher Gleason Score (P=0.001), PSA level at diagnosis (P=<0.0001) and clinical stage (P=0.017) but was not linked to poorer survival. We found that the six previously characterised translocation partners of ETV1 only accounted for 34% of ETV1 re-arrangements (eight out of 23) in this series, with fusion to the androgen-repressed gene C15orf21 representing the commonest event (four out of 23). In 5′-RACE experiments on RNA extracted from formalin-fixed tissue we identified the androgen-upregulated gene ACSL3 as a new 5′-translocation partner of ETV1. These studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer. PMID:18594527

  4. Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer.

    PubMed

    Attard, G; Clark, J; Ambroisine, L; Mills, I G; Fisher, G; Flohr, P; Reid, A; Edwards, S; Kovacs, G; Berney, D; Foster, C; Massie, C E; Fletcher, A; De Bono, J S; Scardino, P; Cuzick, J; Cooper, C S

    2008-07-22

    A fluorescence in situ hybridisation (FISH) assay has been used to screen for ETV1 gene rearrangements in a cohort of 429 prostate cancers from patients who had been diagnosed by trans-urethral resection of the prostate. The presence of ETV1 gene alterations (found in 23 cases, 5.4%) was correlated with higher Gleason Score (P=0.001), PSA level at diagnosis (P=<0.0001) and clinical stage (P=0.017) but was not linked to poorer survival. We found that the six previously characterised translocation partners of ETV1 only accounted for 34% of ETV1 re-arrangements (eight out of 23) in this series, with fusion to the androgen-repressed gene C15orf21 representing the commonest event (four out of 23). In 5'-RACE experiments on RNA extracted from formalin-fixed tissue we identified the androgen-upregulated gene ACSL3 as a new 5'-translocation partner of ETV1. These studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer.

  5. A curated collection of tissue microarray images and clinical outcome data of prostate cancer patients

    PubMed Central

    Zhong, Qing; Guo, Tiannan; Rechsteiner, Markus; Rüschoff, Jan H.; Rupp, Niels; Fankhauser, Christian; Saba, Karim; Mortezavi, Ashkan; Poyet, Cédric; Hermanns, Thomas; Zhu, Yi; Moch, Holger; Aebersold, Ruedi; Wild, Peter J.

    2017-01-01

    Microscopy image data of human cancers provide detailed phenotypes of spatially and morphologically intact tissues at single-cell resolution, thus complementing large-scale molecular analyses, e.g., next generation sequencing or proteomic profiling. Here we describe a high-resolution tissue microarray (TMA) image dataset from a cohort of 71 prostate tissue samples, which was hybridized with bright-field dual colour chromogenic and silver in situ hybridization probes for the tumour suppressor gene PTEN. These tissue samples were digitized and supplemented with expert annotations, clinical information, statistical models of PTEN genetic status, and computer source codes. For validation, we constructed an additional TMA dataset for 424 prostate tissues, hybridized with FISH probes for PTEN, and performed survival analysis on a subset of 339 radical prostatectomy specimens with overall, disease-specific and recurrence-free survival (maximum 167 months). For application, we further produced 6,036 image patches derived from two whole slides. Our curated collection of prostate cancer data sets provides reuse potential for both biomedical and computational studies. PMID:28291248

  6. Phase I Trial of Adenovirus-Mediated IL-12 Gene Transduction in Patients with Recurrent Locally Advanced Prostate Cancer Following Therapy

    DTIC Science & Technology

    2005-10-01

    radiation therapy who are presently not on hormonal therapy. An important part of the screening process is a needle biopsy of the prostate to confirm the...has been amended (see below) to also include patients who had their locally advanced prostate cancer treated with hormonal ablative therapy...the lack of effective therapies for men who have failed definitive radiotherapy or who have locally advanced cancer despite hormone ablative therapy

  7. A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer

    PubMed Central

    Troyer, Dean A; Jamaspishvili, Tamara; Wei, Wei; Feng, Ziding; Good, Jennifer; Hawley, Sarah; Fazli, Ladan; McKenney, Jesse K; Simko, Jeff; Hurtado-Coll, Antonio; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Brooks, James D; Squire, Jeremy A

    2015-01-01

    BACKGROUND Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making. Our objectives were to assess the incidence and ability of PTEN alterations to predict aggressive disease in a multicenter study. METHODS We used recently developed probes optimized for sensitivity and specificity in a four-color FISH deletion assay to study the Canary Retrospective multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed specifically for biomarker validation from radical prostatectomy specimens, and is accompanied by detailed clinical information with long-term follow-up. RESULTS In 612 prostate cancers, the overall rate of PTEN deletion was 112 (18.3%). Hemizygous PTEN losses were present in 55/612 (9.0%) of cancers, whereas homozygous PTEN deletion was observed in 57/612 (9.3%) of tumors. Significant associations were found between PTEN status and pathologic stage (P < 0.0001), seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and Gleason score (P = 0.0002). In logistic regression analysis of clinical and pathological variables, PTEN deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, PTEN homozygous (P = 0.009) deletion was associated with worse post-operative recurrence-free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P < 0.001), and pathologic stage (P = 0.03). CONCLUSION PTEN status assessed by FISH is an independent predictor for recurrence-free survival in

  8. 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.

  9. Prostate Cancer Clinical Trials Group: The University of Michigan Site

    DTIC Science & Technology

    2011-04-01

    Andrew J. Armstrong, William Kevin Kelly, Anna Ferrari, John Hainsworth, Ling Yang, Jonathan Schwartz, Hagop Youssoufian, Celestia S. Higano. Innovative...Sweeney, R. Kurzrock, M.S. Gordon, N.J. Vogelzang, C. Scheffold, M.D. Ballinger , M. Hussain. American Society of Clinical Oncology (ASCO) GU...Laura Jr., C. Lin, A. Sella, E.J. Small, A.I. Spira, U. N. Vaishampayan, N.J. Vogelzang, C. Scheffold, M.D. Ballinger , F. Schimmoller, D.C. Smith. Oral

  10. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial

    PubMed Central

    Warde, Padraig; Mason, Malcolm; Ding, Keyue; Kirkbride, Peter; Brundage, Michael; Cowan, Richard; Gospodarowicz, Mary; Sanders, Karen; Kostashuk, Edmund; Swanson, Greg; Barber, Jim; Hiltz, Andrea; Parmar, Mahesh KB; Sathya, Jinka; Anderson, John; Hayter, Charles; Hetherington, John; Sydes, Matthew R; Parulekar, Wendy

    2011-01-01

    Summary Background Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer. Methods Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65–69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. Results Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4–8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70–78 vs 66%, 60–70; hazard ratio [HR] 0·77, 95% CI 0·61–0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5%) in the ADT only group, two (0·3%) in the ADT and RT group; diarrhoea grade >3, four patients (0·7%) vs eight (1·3%); urinary toxicity grade >3, 14 patients (2·3%) in both groups). Interpretation The benefits of combined

  11. Hypofractionated External-Beam Radiotherapy for Prostate Cancer

    PubMed Central

    Cho, L. Chinsoo; Timmerman, Robert; Kavanagh, Brian

    2013-01-01

    There are radiobiological rationales supporting hypofractionated radiotherapy for prostate cancer. The recent advancements in treatment planning and delivery allow sophisticated radiation treatments to take advantage of the differences in radiobiology of prostate cancer and the surrounding normal tissues. The preliminary results from clinical studies indicate that abbreviated fractionation programs can result in successful treatment of localized prostate cancer without escalation of late toxicity. PMID:23533777

  12. The influence of the local effect model parameters on the prediction of the tumor control probability for prostate cancer.

    PubMed

    Chanrion, M-A; Sauerwein, W; Jelen, U; Wittig, A; Engenhart-Cabillic, R; Beuve, M

    2014-06-21

    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 [Formula: see text]. 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.

  13. 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.

  14. 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

  15. 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.

  16. Patient Positioning Based on a Radioactive Tracer Implanted in Patients With Localized Prostate Cancer: A Performance and Safety Evaluation

    SciTech Connect

    Kruijf, Willy J.M. de; Verstraete, Jan; Neustadter, David; Corn, Benjamin W.; Hol, Sandra; Venselaar, Jack L.M.; Davits, Rob J.; Wijsman, Bart P.; Van den Bergh, Laura; Budiharto, Tom; Oyen, Raymond; Haustermans, Karin; Poortmans, Philip M.P.

    2013-02-01

    Purpose: To evaluate the performance and safety of a radiation therapy positioning system (RealEye) based on tracking a radioactive marker (Tracer) implanted in patients with localized prostate cancer. Methods and Materials: We performed a single-arm multi-institutional trial in 20 patients. The iridium-192 ({sup 192}Ir)-containing Tracer was implanted in the patient together with 4 standard gold seed fiducials. Patient prostate-related symptoms were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Computed tomography (CT) was performed for treatment planning, during treatment, and after treatment to evaluate the migration stability of the Tracer. At 5 treatment sessions, cone beam CT was performed to test the positioning accuracy of the RealEye. Results: The Tracer was successfully implanted in all patients. No device or procedure-related adverse events occurred. Changes in IPSS scores were limited. The difference between the mean change in Tracer-fiducial distance and the mean change in fiducial-fiducial distance was -0.39 mm (95% confidence interval [CI] upper boundary, -0.22 mm). The adjusted mean difference between Tracer position according to RealEye and the Tracer position on the CBCT for all patients was 1.34 mm (95% CI upper boundary, 1.41 mm). Conclusions: Implantation of the Tracer is feasible and safe. Migration stability of the Tracer is good. Prostate patients can be positioned and monitored accurately by using RealEye.

  17. 1.5-Tesla Multiparametric-Magnetic Resonance Imaging for the detection of clinically significant prostate cancer

    PubMed Central

    POPITA, CRISTIAN; POPITA, ANCA RALUCA; SITAR-TAUT, ADELA; PETRUT, BOGDAN; FETICA, BOGDAN; COMAN, IOAN

    2017-01-01

    Background and aim Multiparametric-magnetic resonance imaging (mp-MRI) is the main imaging modality used for prostate cancer detection. The aim of this study is to evaluate the diagnostic performance of mp-MRI at 1.5-Tesla (1.5-T) for the detection of clinically significant prostate cancer. Methods In this ethical board approved prospective study, 39 patients with suspected prostate cancer were included. Patients with a history of positive prostate biopsy and patients treated for prostate cancer were excluded. All patients were examined at 1.5-T MRI, before standard transrectal ultrasonography–guided biopsy. Results The overall sensitivity, specificity, positive predictive value and negative predictive value for mp-MRI were 100%, 73.68%, 80% and 100%, respectively. Conclusion Our results showed that 1.5 T mp-MRI has a high sensitivity for detection of clinically significant prostate cancer and high negative predictive value in order to rule out significant disease. PMID:28246496

  18. Clinical consequences of relative biological effectiveness variations in proton radiotherapy of the prostate, brain and liver.

    PubMed

    Carabe, Alejandro; España, Samuel; Grassberger, Clemens; Paganetti, Harald

    2013-04-07

    Proton relative biological effectiveness (RBE) is known to depend on the (α/β)x of irradiated tissues, with evidence of ∼60% variation over (α/β)x values from 1-10 Gy. The range of (α/β)x values reported for prostate tumors (1.2-5.0 Gy), brain tumors (10-15 Gy) and liver tumors (13-17 Gy) imply that the proton RBE for these tissues could vary significantly compared to the commonly used generic value of 1.1. Our aim is to evaluate the impact of this uncertainty on the proton dose in Gy(RBE) absorbed in normal and tumor tissues. This evaluation was performed for standard and hypofractionated regimens. RBE-weighted total dose (RWTD) distributions for 15 patients (five prostate tumors, five brain tumors and five liver tumors) were calculated using an in-house developed RBE model as a function of dose, dose-averaged linear energy transfer (LETd) and (α/β)x. Variations of the dose-volume histograms (DVHs) for the gross tumor volume (GTV) and the organs at risk due to changes of (α/β)x and fractionation regimen were calculated and the RWTD received by 10% and 90% of the organ volume reported. The goodness of the plan, bearing the uncertainties, was then evaluated compared to the delivered plan, which considers a constant RBE of 1.1. For standard fractionated regimens, the prostate tumors, liver tumors and all critical structures in the brain showed typically larger RBE values than 1.1. However, in hypofractionated regimens lower values of RBE than 1.1 were observed in most cases. Based on DVH analysis we found that the RBE variations were clinically significant in particular for the prostate GTV and the critical structures in the brain. Despite the uncertainties in the biological input parameters when estimating RBE values, the results show that the use of a variable RBE with dose, LETd and (α/β)x could help to further optimize the target dose in proton treatment planning. Most importantly, this study shows that the consideration of RBE variations could

  19. Clinical consequences of relative biological effectiveness variations in proton radiotherapy of the prostate, brain and liver

    NASA Astrophysics Data System (ADS)

    Carabe, Alejandro; España, Samuel; Grassberger, Clemens; Paganetti, Harald

    2013-04-01

    Proton relative biological effectiveness (RBE) is known to depend on the (α/β)x of irradiated tissues, with evidence of ˜60% variation over (α/β)x values from 1-10 Gy. The range of (α/β)x values reported for prostate tumors (1.2-5.0 Gy), brain tumors (10-15 Gy) and liver tumors (13-17 Gy) imply that the proton RBE for these tissues could vary significantly compared to the commonly used generic value of 1.1. Our aim is to evaluate the impact of this uncertainty on the proton dose in Gy(RBE) absorbed in normal and tumor tissues. This evaluation was performed for standard and hypofractionated regimens. RBE-weighted total dose (RWTD) distributions for 15 patients (five prostate tumors, five brain tumors and five liver tumors) were calculated using an in-house developed RBE model as a function of dose, dose-averaged linear energy transfer (LETd) and (α/β)x. Variations of the dose-volume histograms (DVHs) for the gross tumor volume (GTV) and the organs at risk due to changes of (α/β)x and fractionation regimen were calculated and the RWTD received by 10% and 90% of the organ volume reported. The goodness of the plan, bearing the uncertainties, was then evaluated compared to the delivered plan, which considers a constant RBE of 1.1. For standard fractionated regimens, the prostate tumors, liver tumors and all critical structures in the brain showed typically larger RBE values than 1.1. However, in hypofractionated regimens lower values of RBE than 1.1 were observed in most cases. Based on DVH analysis we found that the RBE variations were clinically significant in particular for the prostate GTV and the critical structures in the brain. Despite the uncertainties in the biological input parameters when estimating RBE values, the results show that the use of a variable RBE with dose, LETd and (α/β)x could help to further optimize the target dose in proton treatment planning. Most importantly, this study shows that the consideration of RBE variations could

  20. Localization of a Portion of an Endorectal Balloon for Prostate Image-Guided Radiation Therapy Using Cone-Beam Tomosynthesis: A Feasibility Study

    SciTech Connect

    Ng, Sook Kien; Zygmanski, Piotr; Lyatskaya, Yulia; D'Amico, Anthony V.; Cormack, Robert A.

    2012-06-01

    Purpose: To assess the feasibility of using cone-beam tomosynthesis (CBTS) to localize the air-tissue interface for the application of prostate image-guided radiation therapy using an endorectal balloon for immobilization and localization. Methods and Materials: A Feldkamp-David-Kress-based CBTS reconstruction was applied to selected sets of cone-beam computed tomography (CBCT) projection data to simulate volumetric imaging achievable from tomosynthesis for a limited range of scan angles. Projection data were calculated from planning CT images of 10 prostate cancer patients treated with an endorectal balloon, as were experimental CBCT projections for a pelvic phantom in two patients. More than 50 points at the air-tissue interface were objectively identified by an intensity-based interface-finding algorithm. Using three-dimensional point sets extracted from CBTS images compared with points extracted from corresponding CBCT images, the relative shift resulting from a reduced scan angle was determined. Because the CBCT and CBTS images were generated from the same projection data set, shift identified was presumed to be due to distortions introduced by the tomosynthesis technique. Results: Scans of {>=}60 Degree-Sign were shown to be able to localize an air-tissue interface near the isocenter with accuracy on the order of a millimeter. The accuracy was quantified in terms of the mean discrepancy as a function of reconstruction angle. Conclusion: This work provides an understanding of the effect of scan angle used in localization of a portion of an endorectal balloon by means of CBTS. CBTS with relatively small scan angles is capable of accurately localizing an extended interface near the isocenter and may provide clinically relevant measurements to guide IGRT treatments while reducing imaging radiation to the patient.

  1. Hypofractionated proton boost combined with external beam radiotherapy for treatment of localized prostate cancer.

    PubMed

    Johansson, Silvia; Aström, Lennart; Sandin, Fredrik; Isacsson, Ulf; Montelius, Anders; Turesson, Ingela

    2012-01-01

    Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU) and gastrointestinal (GI) toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity.

  2. Hypofractionated Proton Boost Combined with External Beam Radiotherapy for Treatment of Localized Prostate Cancer

    PubMed Central

    Johansson, Silvia; Åström, Lennart; Sandin, Fredrik; Isacsson, Ulf; Montelius, Anders; Turesson, Ingela

    2012-01-01

    Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU) and gastrointestinal (GI) toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity. PMID:22848840

  3. Prostate cancer screening characteristics in men with BRCA1/2 mutations attending a high-risk prevention clinic

    PubMed Central

    Walker, Richard; Louis, Alyssa; Berlin, Alejandro; Horsburgh, Sheri; Bristow, Robert G.; Trachtenberg, John

    2014-01-01

    Introduction: The prostate-specific antigen (PSA) era and resultant early detection of prostate cancer has presented clinicians with the challenge of distinguishing indolent from aggressive tumours. Mutations in the BRCA1/2 genes have been associated with prostate cancer risk and prognosis. We describe the prostate cancer screening characteristics of BRCA1/2 mutation carriers, who may be classified as genetically-defined high risk, as compared to another high-risk cohort of men with a family history of prostate cancer to evaluate the utility of a targeted screening approach for these men. Methods: We reviewed patient demographics, clinical screening characteristics, pathological features, and treatment outcomes between a group of BRCA1 or BRCA2 mutation carriers and age-matched men with a family history of prostate cancer followed at our institutional Prostate Cancer Prevention Clinic from 1995 to 2012. Results: Screening characteristics were similar between the mutation carriers (n = 53) and the family history group (n = 53). Some cancers would be missed in both groups by using a PSA cut-off of >4 ug/L. While cancer detection was higher in the family history group (21% vs. 15%), the mutation carrier group was more likely to have intermediate- or high-risk disease (88% vs. 36%). BRCA2 mutation carriers were more likely to have aggressive disease, biological recurrence, and distant metastasis. Conclusions: In our cohort, regular screening appears justified for detecting prostate cancer in BRCA1 and BRCA2 carriers and other high-risk populations. Lowering PSA cut-offs and defining monitoring of PSA velocity as part of the screening protocol may be useful. BRCA2 is associated with more aggressive disease, while the outcome for BRCA1 mutation carriers requires further study. Large multinational studies will be important to define screening techniques for this unique high-risk population. PMID:25485004

  4. Clinical application of sonoelastography in thyroid, prostate, kidney, pancreas, and deep venous thrombosis.

    PubMed

    Anvari, Arash; Barr, Richard G; Dhyani, Manish; Samir, Anthony E

    2015-04-01

    This article reviews the clinical applications of current ultrasound elastography methods in non-hepatic conditions including thyroid nodules, prostate cancer, chronic kidney disease, solid renal lesions, pancreatic lesions, and deep vein thrombosis. Pathophysiology alters tissue mechanical properties via ultrastructural changes including fibrosis, increased cellularity, bleeding, and necrosis, creating a target biomarker, which can be imaged qualitatively or quantitatively with US elastography. US elastography methods can add information to conventional US methods and improve the diagnostic performance of conventional US in a range of disease processes.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. DNA vaccination for prostate cancer, from preclinical to clinical trials - where we stand?

    PubMed

    Ahmad, Sarfraz; Sweeney, Paul; Sullivan, Gerald C; Tangney, Mark

    2012-10-09

    Development of various vaccines for prostate cancer (PCa) is becoming an active research area. PCa vaccines are perceived to have less toxicity compared with the available cytotoxic agents. While various immune-based strategies can elicit anti-tumour responses, DNA vaccines present increased efficacy, inducing both humoural and cellular immunity. This immune activation has been proven effective in animal models and initial clinical trials are encouraging. However, to validate the role of DNA vaccination in currently available PCa management paradigms, strong clinical evidence is still lacking. This article provides an overview of the basic principles of DNA vaccines and aims to provide a summary of preclinical and clinical trials outlining the benefits of this immunotherapy in the management of PCa.

  11. Prostate PDT dosimetry

    PubMed Central

    Zhu, Timothy C.; Finlay, Jarod C.

    2015-01-01

    Summary We provide a review of the current state of dosimetry in prostate photodynamic therapy (PDT). PDT of the human prostate has been performed with a number of different photosensitizers and with a variety of dosimetry schemes. The simplest clinical light dose prescription is to quantify the total light energy emitted per length (J/cm) of cylindrical diffusing fibers (CDF) for patients treated with a defined photosensitizer injection per body weight. However, this approach does not take into account the light scattering by tissue and usually underestimates the local light fluence rate, and consequently the fluence. Techniques have been developed to characterize tissue optical properties and light fluence rates in vivo using interstitial measurements during prostate PDT. Optical methods have been developed to characterize tissue absorption and scattering spectra, which in turn provide information about tissue oxygenation and drug concentration. Fluorescence techniques can be used to quantify drug concentrations and photobleaching rates of photosensitizers. PMID:25046988

  12. 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.

  13. 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.

  14. 1.5T MRI-guided trans-perineal laser ablation of locally recurrent prostate adenocarcinoma

    NASA Astrophysics Data System (ADS)

    McPhail, E. Frederick; Mynderse, Lance A.; Callstrom, Matthew R.; Gorny, Krzysztof R.; McNichols, Roger J.; Atwell, Thomas D.; Gettman, Matthew T.; Amrami, Kimberly K.; Kawashima, Akira; Woodrum, David A.

    2010-02-01

    Introduction: Biochemical recurrence of prostate cancer after definitive therapy with radical prostatectomy (RP) is known to occur between 25-30%. We present the first known case of 1.5T MRI guided ablation using laser interstitial thermal therapy (LITT) for locally recurrent prostate cancer following RP. Methods: The patient elected to undergo MRI-guided LITT of the biopsy proven cancer recurrence using an FDAapproved MRI compatible, 980nm, 15-watt laser system with MR thermometry. Under T2-weighted MR(1.5T Siemens) imaging, guidance and targeting of the lesions with trans-perineal placement of laser applicators. Multiple cycles of laser energy were used to ablate the tumor. A MRI-compatible urethral cooling catheter was placed to prevent urethral thermal damage. Results: Intra-procedural temperature mapping allowed continuous monitoring of the ablation zone and permitted ablation control until tumor coverage was achieved. Additionally, the protective cooling effects of the urethral cooling catheter could also be seen with the temperature mapping. Post-ablation gadolinium and T2 weighted MR imaging demonstrated an ablation defect encompassing the recurrent tumor with no residual hyper-enhancing nodules. Three month follow-up shows no residual or recurrent tumor seen on MR imaging. Conclusion: This represents the first known, successful, MRI-guided, LITT procedures at 1.5T for locally recurrent prostate adenocarcinoma following RP.

  15. The Potential Role of Lycopene for the Prevention and Therapy of Prostate Cancer: From Molecular Mechanisms to Clinical Evidence

    PubMed Central

    Holzapfel, Nina Pauline; Holzapfel, Boris Michael; Champ, Simon; Feldthusen, Jesper; Clements, Judith; Hutmacher, Dietmar Werner

    2013-01-01

    Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. PMID:23857058

  16. Use of 5-α-Reductase Inhibitors for Prostate Cancer Chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline

    PubMed Central

    Kramer, Barnett S.; Hagerty, Karen L.; Justman, Stewart; Somerfield, Mark R.; Albertsen, Peter C.; Blot, William J.; Ballentine Carter, H.; Costantino, Joseph P.; Epstein, Jonathan I.; Godley, Paul A.; Harris, Russell P.; Wilt, Timothy J.; Wittes, Janet; Zon, Robin; Schellhammer, Paul

    2009-01-01

    Purpose To develop an evidence-based guideline on the use of 5-α-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. Methods The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. Results The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. Conclusion Asymptomatic men with a prostate-specific antigen (PSA) ≤ 3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI. PMID:19252137

  17. Treating Localized Prostate Cancer: A Review of the Research for Adults

    MedlinePlus

    ... 2014 Related Products for this Topic Research Protocol Mar. 29, 2013 Disposition of Comments Report Apr. 16, ... Score (T-score) The T-score tells how far your prostate cancer has grown. T1 : The cancer ...

  18. Intensity Modulated Radiation Therapy Dose Painting for Localized Prostate Cancer Using {sup 11}C-choline Positron Emission Tomography Scans

    SciTech Connect

    Chang, Joe H.; Lim Joon, Daryl; Lee, Sze Ting; Gong, Sylvia J.; Anderson, Nigel J.; Scott, Andrew M.; Davis, Ian D.; Clouston, David; Bolton, Damien; Hamilton, Christopher S.; Khoo, Vincent

    2012-08-01

    Purpose: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using {sup 11}C-choline positron emission tomography PET scans in patients with localized prostate cancer. Methods and Materials: This was an RT planning study of 8 patients with prostate cancer who had {sup 11}C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV{sub 60%} and SUV{sub 70%}). Three IMRT plans were generated for each patient: PLAN{sub 78}, which consisted of whole-prostate radiation therapy to 78 Gy; PLAN{sub 78-90}, which consisted of whole-prostate RT to 78 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy; and PLAN{sub 72-90}, which consisted of whole-prostate RT to 72 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP{sub PET}) and on prostatectomy-defined volumes (TCP{sub path}), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. Results: All plans for all patients reached prescription doses while adhering to dose constraints. TCP{sub PET} values for PLAN{sub 78}, PLAN{sub 78-90}, and PLAN{sub 72-90} were 65%, 97%, and 96%, respectively. TCP{sub path} values were 71%, 97%, and 89%, respectively. Both PLAN{sub 78-90} and PLAN{sub 72-90} had significantly higher TCP{sub PET} (P=.002 and .001) and TCP{sub path} (P<.001 and .014) values than PLAN{sub 78}. PLAN{sub 78-90} and PLAN{sub 72-90} were not significantly different in terms of TCP{sub PET} or TCP{sub path}. There were no significant differences in rectal NTCPs between the 3 plans. Conclusions: IMRT dose painting for

  19. 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

  20. 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

  1. 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

  2. 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

  3. Interfraction rotation of the prostate as evaluated by kilovoltage X-ray fiducial marker imaging in intensity-modulated radiotherapy of localized prostate cancer.

    PubMed

    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° 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° with standard deviations of 2.01, 2.30, and 3.95°, respectively. The systematic uncertainty per patient for prostate rotation was estimated with 2.30, 1.56, and 4.13° and the mean random components with 1.81, 2.02, and 3.09°. 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 suitable strategies for correction.

  4. 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

  5. Brachytherapy for Patients With Prostate Cancer: American Society of Clinical Oncology/Cancer Care Ontario Joint Guideline Update.

    PubMed

    Chin, Joseph; Rumble, R Bryan; Kollmeier, Marisa; Heath, Elisabeth; Efstathiou, Jason; Dorff, Tanya; Berman, Barry; Feifer, Andrew; Jacques, Arthur; Loblaw, D Andrew

    2017-03-27

    Purpose To jointly update the Cancer Care Ontario guideline on brachytherapy for patients with prostate cancer to account for new evidence. Methods An Update Panel conducted a targeted systematic literature review and identified more recent randomized controlled trials comparing dose-escalated external beam radiation therapy (EBRT) with brachytherapy in men with prostate cancer. Results Five randomized controlled trials provided the evidence for this update. Recommendations For patients with low-risk prostate cancer who require or choose active treatment, low-dose rate brachytherapy (LDR) alone, EBRT alone, and/or radical prostatectomy (RP) should be offered to eligible patients. For patients with intermediate-risk prostate cancer choosing EBRT with or without androgen-deprivation therapy, brachytherapy boost (LDR or high-dose rate [HDR]) should be offered to eligible patients. For low-intermediate risk prostate cancer (Gleason 7, prostate-specific antigen < 10 ng/mL or Gleason 6, prostate-specific antigen, 10 to 20 ng/mL), LDR brachytherapy alone may be offered as monotherapy. For patients with high-risk prostate cancer receiving EBRT and androgen-deprivation therapy, brachytherapy boost (LDR or HDR) should be offered to eligible patients. Iodine-125 and palladium-103 are each reasonable isotope options for patients receiving LDR brachytherapy; no recommendation can be made for or against using cesium-131 or HDR monotherapy. Patients should be encouraged to participate in clinical trials to test novel or targeted approaches to this disease. Additional information is available at www.asco.org/Brachytherapy-guideline and www.asco.org/guidelineswiki .

  6. Morphological and immunohistochemical identification of epithelial-to-mesenchymal transition in clinical prostate cancer

    PubMed Central

    Kolijn, Kimberley; Verhoef, Esther I.; van Leenders, Geert J.L.H.

    2015-01-01

    Epithelial-to-mesenchymal transition (EMT) is a process known to be associated with aggressive tumor behavior, metastasis and treatment resistance. It is characterized by coincidental upregulation of mesenchymal markers such as vimentin, fibronectin and N-cadherin concurrent with E-cadherin downregulation. Studies on EMT are generally performed in cell lines and mouse models, while the histopathological and phenotypical properties in clinical prostate cancer (PCa) are still unclear. The objective of this study was to identify EMT in PCa patients. We demonstrated that N-cadherin, vimentin and fibronectin were generally not co-expressed in corresponding tumor regions. Immunofluorescent double stainings confirmed that co-expression of mesenchymal markers was uncommon, as we found no prostate cancer cells that co-expressed N-cadherin with fibronectin and only rare (<1%) cells that co-expressed N-cadherin with vimentin. Downregulation of E-cadherin was demonstrated in all N-cadherin positive tumor cells, but not in vimentin or fibronectin positive tumor cells. We further analyzed N-cadherin expression in morphologically distinct PCa growth patterns in a radical prostatectomy cohort (n = 77) and found that N-cadherin is preferentially expressed in ill-defined Gleason grade 4 PCa. In conclusion, we demonstrate that N-cadherin is the most reliable marker for EMT in clinical PCa and is preferentially expressed in ill-defined Gleason grade 4 growth pattern. PMID:26041890

  7. 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.

  8. Early hormonal data from a multicentre phase II trial using transdermal oestrogen patches as first-line hormonal therapy in patients with locally advanced or metastatic prostate cancer

    PubMed Central

    Langley, Ruth E.; Godsland, Ian F.; Kynaston, Howard; Clarke, Noel W.; Rosen, Stuart D.; Morgan, Rachel C.; Pollock, Philip; Kockelbergh, Roger; Lalani, El-Nasir; Dearnaley, David; Parmar, Mahesh; Abel, Paul D.

    2008-01-01

    OBJECTIVE To assess the hormonal effects of Fem7® (Merck, KGaA, Darmstadt, Germany) 100 μg transdermal oestrogen patches on men undergoing first-line androgen-deprivation therapy for prostate cancer. PATIENTS AND METHODS PATCH is a multicentre, randomized, phase II trial for men with locally advanced or metastatic prostate cancer, comparing luteinizing hormone-releasing hormone agonist therapy with oestrogen patches. To assess the dosing schedule for the patches, as this was the first time that this brand of patch had been used in men, and to reassure patients and participating clinicians, the Independent Data Monitoring Committee agreed to early release of hormonal data from this study. RESULTS Oestradiol, testosterone and prostate-specific antigen (PSA) levels are presented for the first group of 14 patients who received the patches (with 1 withdrawal) and for whom there were ≥12 weeks of follow-up by March 2007. After 12 weeks, testosterone levels (nmol/L) in eight of the 13 patients were <1.7, two were 1.7–2 and three were >2. The median (range) serum oestradiol levels was 442 (52.1–1542) pmol/L and all patients had a PSA response, with eight having a PSA level of <4 ng/mL. CONCLUSION These results confirm that oestrogen patches produce castrate levels of testosterone and concomitant PSA responses. They also highlighted the potential differences between different brands of oestrogen patches, and the need to monitor hormonal response, toxicity and efficacy until more experience with oestrogen patches for this clinical indication is obtained. The number of patches recommended in the PATCH study has now been increased. PMID:18422771

  9. A Pilot Study of Catheter-Based Ultrasound Hyperthermia with HDR Brachytherapy for Treatment of Locally Advanced Cancer of the Prostate and Cervix

    NASA Astrophysics Data System (ADS)

    Diederich, Chris J.; Wootton, Jeff; Prakash, Punit; Salgaonkar, Vasant; Juang, Titania; Scott, Serena; Chen, Xin; Cunha, Adam; Pouliot, Jean; Hsu, I. C.

    2011-09-01

    Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within temporary HDR brachytherapy implants during radiation therapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies. A pilot study of the combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling software can monitor and regulate frequency and power to each transducer section as required during the procedure. Interstitial applicators consist of multiple transducer sections of 2-4 cm length×180 deg and 3-4 cm×360 deg. heating patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a 6 mm OD plastic tandem catheter within the cervix, consists of 2-3 transducers x dual 180 or 360 deg sectors. 3D temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best configure and position the applicators within the catheters, and to determine optimal base power levels to each transducer section. To date we have treated eight cervix implants and four prostate implants. 100% of treatments achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the hyperthermia target volume (HTV) and clinical target volume (CTV) are reported. Catheter-based ultrasound hyperthermia with HDR appears feasible with therapeutic temperature coverage of the target volume within the prostate or cervix while sparing surrounding more sensitive regions.

  10. 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.

  11. 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.

  12. The Early Result of Whole Pelvic Radiotherapy and Stereotactic Body Radiotherapy Boost for High-Risk Localized Prostate Cancer

    PubMed Central

    Lin, Yu-Wei; Lin, Li-Ching; Lin, Kuei-Li

    2014-01-01

    Purpose: The rationale for hypofractionated radiotherapy in the treatment of prostate cancer is based on the modern understanding of radiobiology and advances in stereotactic body radiotherapy (SBRT) techniques. Whole-pelvis irradiation combined with SBRT boost for high-risk prostate cancer might escalate biologically effective dose without increasing toxicity. Here, we report our 4-year results of SBRT boost for high-risk localized prostate cancer. Methods and Materials: From October 2009 to August 2012, 41 patients newly diagnosed, high-risk or very high-risk (NCCN definition) localized prostate cancer were treated with whole-pelvis irradiation and SBRT boost. The whole pelvis dose was 45 Gy (25 fractions of 1.8 Gy). The SBRT boost dose was 21 Gy (three fractions of 7 Gy). Ninety percent of these patients received hormone therapy. The toxicities of gastrointestinal (GI) and genitourinary (GU) tracts were scored by Common Toxicity Criteria Adverse Effect (CTCAE v3.0). Biochemical failure was defined by Phoenix definition. Results: Median follow-up was 42 months. Mean PSA before treatment was 44.18 ng/ml. Mean PSA level at 3, 6, 12, 18, and 24 months was 0.94, 0.44, 0.13, 0.12, and 0.05 ng/ml, respectively. The estimated 4-year biochemical failure-free survival was 91.9%. Three biochemical failures were observed. GI and GU tract toxicities were minimal. No grade 3 acute GU or GI toxicity was noted. During radiation therapy, 27% of the patient had grade 2 acute GU toxicity and 12% had grade 2 acute GI toxicity. At 3 months, most toxicity scores had returned to baseline. At the last follow-up, there was no grade 3 late GU or GI toxicity. Conclusions: Whole-pelvis irradiation combined with SBRT boost for high-risk localized prostate cancer is feasible with minimal toxicity and encouraging biochemical failure-free survival. Continued accrual and follow-up would be necessary to confirm the biochemical control rate and the toxicity profiles. PMID

  13. 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

  14. 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

  15. Immunoscintigraphic localization of inflammatory lesions: clinical experience.

    PubMed

    Seybold, K; Locher, J T; Coosemans, C; Andres, R Y; Schubiger, P A; Bläuenstein, P

    1988-01-01

    This clinical study was based on the experimental results reported in the two preceding papers, showing that the highly selective affinity of the 123I-anti-CEA monoclonal antibody 47 (123I-Mabgc) for human granulocytes makes this compound suitable for the immunoscintigraphic detection of inflammatory lesions. Forty five patients with suspected infections have been studied after infusion of 4 mCi (148 MBq) 123I-Mabgc corresponding to 120 micrograms labeled protein. No adverse reactions have been seen. Because of the high number of labeled cells, the quality of the images was excellent. SPECT was performed in 15 cases in order to define the extent of the lesion. Infectious foci were usually seen 3-5 h postinjection, but the unimpaired function of the granulocytes guarantees diagnostically relevant examinations over a much longer period of time. Scans were read as being negative if no pathological accumulation of activity was detected after 24 h. The new scanning method is technically easy to perform and provides distinct advantages over other techniques necessitating in vitro labeling of the white blood cells. Therefore, recommended indications are acute infections of unknown origin or extent, especially recurrent episodes of osteomyelitis and infections of joint prostheses.

  16. Why do men choose one treatment over another?: a review of patient decision making for localized prostate cancer.

    PubMed

    Zeliadt, Steven B; Ramsey, Scott D; Penson, David F; Hall, Ingrid J; Ekwueme, Donatus U; Stroud, Leonard; Lee, Judith W

    2006-05-01

    Treatment choices for localized prostate cancer appear to vary widely, although it is unclear whether this variation is a result of patient values or other factors. The authors conducted a systematic review of the literature, identifying 70 articles that focused on prostate cancer decision making. Studies suggest that men consider several issues when making treatment decisions. The authors found conflicting evidence regarding the importance that men place on cancer eradication, with considerable variation in how patients interpret evidence regarding treatment efficacy. The number of physicians that men see and the importance of the physician recommendation were found to vary considerably. Although men stated that side effects are important, few patients reported that side effect factors ultimately influenced their treatment choice. To the authors' knowledge, there is little research regarding how patients' personal values shape and influence their decision, or the role of race/ethnicity or socioeconomic status in preferences for treatment. The authors conclude that variations in treatment decisions may be more indicative of differences in the information patients receive rather than truly reflective of underlying patient preferences. Considerable progress is needed in helping patients fully understand how to balance the complex issues surrounding prostate cancer treatment decision making.

  17. Rare Paravertebral and Skull Base Metastases in Prostate Cancer

    PubMed Central

    Samuel, Gbeminiyi; Isbell, Amir; Ogbonna, Onyekachi; Iftikhar, Hasan; Sakruti, Susmita; Atanda, Adebayo; Manchandani, Raj P.

    2016-01-01

    Prostate cancer is the most commonly diagnosed visceral cancer in the United States. A majority of cases exhibit an insidious course and nonaggressive tumor behavior. Prostate cancer can manifest as lesions which remain localized, regionally invading or metastasize to lymph nodes, bones, and lungs. Here, we report a unique case of metastatic prostate cancer to the right upper mediastinum, presenting as a paravertebral mass within 2 years of initial tissue diagnosis. Paravertebral spread has not been described for prostate cancer, and herein, we discuss the clinical presentation, diagnostic workup, and possible therapeutic options available in light of the literature. PMID:27920711

  18. Prostate-specific antigen kinetics following hypofractionated stereotactic body radiotherapy boost as post-external beam radiotherapy versus conventionally fractionated external beam radiotherapy for localized prostate cancer

    PubMed Central

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

    2015-01-01

    Background Stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. The purpose of this study was to compare the prostate-specific antigen (PSA) kinetics between conventionally fractionated external beam radiotherapy (CF-EBRT) and SBRT boost after whole pelvis EBRT (WP-EBRT) in localized prostate cancer. Methods A total of 77 patients with localized prostate cancer [T-stage, T1–T3; Gleason score (GS) 5–9; PSA < 20 ng/mL] were enrolled. A total of 35 patients were treated with SBRT boost (21 Gy in 3 fractions) after WP-EBRT and 42 patients were treated with CF-EBRT (45 Gy WP-EBRT and boost of 25.2–30.6 Gy in 1.8-Gy fractions). PSA nadir and rate of change in PSA (slope) were calculated and compared. Results With a median follow-up of 52.4 months (range, 14–74 months), the median PSA nadir and slope for SBRT boost were 0.29 ng/mL and −0.506, −0.235, −0.129, and −0.092 ng/mL/mo, respectively, for durations of 1 year, 2 years, 3 years, and 4 years postradiotherapy. Similarly, for CF-EBRT, the median PSA nadir and slopes were 0.39 ng/mL and −0.720 ng/mL/mo, −0.204 ng/mL/mo, −0.121 ng/mL/mo, and −0.067 ng/mL/mo, respectively. The slope of CF-EBRT was significantly different with a greater median rate of change for 1 year postradiotherapy than that of SBRT boost (P = 0.018). Contrastively, the slopes of SBRT boost for durations of 2 years, 3 years, and 4 years tended to be continuously greater than that of CF-EBRT. The significantly lower PSA nadir was observed in SBRT boost (median nadir 0.29 ng/mL) compared with CF-EBRT (median nadir 0.35 ng/mL, P = 0.025). Five-year biochemical failure (BCF) free survival was 94.3% for SBRT boost and 78.6% for CF-EBRT (P = 0.012). Conclusion Patients treated with SBRT boost after WP-EBRT experienced a lower PSA nadir and there tended to be a continuously greater rate of decline of PSA for durations of 2 years, 3 years, and

  19. Enhanced expression of centromere protein F predicts clinical progression and prognosis in patients with prostate cancer.

    PubMed

    Zhuo, Yang-Jia; Xi, Ming; Wan, Yue-Ping; Hua, Wei; Liu, Yuan-Ling; Wan, Song; Zhou, Yu-Lin; Luo, Hong-Wei; Wu, Shu-Lin; Zhong, Wei-De; Wu, Chin-Lee

    2015-04-01

    Centromere protein F (CENPF) is a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis. Previous studies have demonstrated that the upregulation of CENPF may be used as a proliferation marker of malignant cell growth in tumors. The overexpression of CENPF has also been reported to be associated with a poor prognosis in human cancers. However, the clinical significance of CENPF in prostate cancer (PCa) has not yet been fully elucidated. Thus, the aim of the present study was to determine the association of CENPF with tumor progression and prognosis in patients with PCa. The expression of CENPF at the protein level in human PCa and non-cancerous prostate tissues was detected by immunohistochemical analysis, which was further validated using a microarray-based dataset (NCBI GEO accession no: GSE21032) at the mRNA level. Subsequently, the association of CENPF expression with the clinicopathological characteristics of the patients with PCa was statistically analyzed. Immunohistochemistry and dataset analysis revealed that CENPF expression was significantly increased in the PCa tissues compared with the non-cancerous prostate tissues [immunoreactivity score (IRS): PCa, 177.98 ± 94.096 vs. benign, 121.30 ± 89.596, P < 0.001; mRNA expression in the dataset: PCa, 5.67 ± 0.47 vs. benign, 5.40 ± 0.11; P < 0.001]. Additionally, as revealed by the dataset, the upregulation of CENPF mRNA expression in the PCa tissues significantly correlated with a higher Gleason score (GS, P = 0.005), an advanced pathological stage (P = 0.008), the presence of metastasis (P < 0.001), a shorter overall survival (P=0.003) and prostate-specific antigen (PSA) failure (P < 0.001). Furthermore, both univariate and multivariate analyses revealed that the upregulation of CENPF was an independent predictor of poor biochemical recurrence (BCR)-free survival (P < 0.001 and P = 0.012, respectively). Our data suggest that the increased expression of CENPF

  20. Clinical and Biological Significance of KISS1 Expression in Prostate Cancer

    PubMed Central

    Wang, Honghe; Jones, Jacqueline; Turner, Timothy; He, Qinghua P.; Hardy, Shana; Grizzle, William E.; Welch, Danny R.; Yates, Clayton

    2012-01-01

    For men in the United States, prostate cancer (PCa) is the most frequent malignancy and the second leading cause of cancer mortality. The metastatic spread of PCa is responsible for most deaths related to PCa. Although KISS1 functions as a metastasis suppressor in various cancers, its expression levels and functions in PCa development and progression remain undetermined. The goals of this study were to correlate the expression levels of KISS1 in PCas with clinicopathologic characteristics and to assess the biological relevance of KISS1 to the viability and motility of PCa cells. Strong KISS1 staining was detected in benign prostate tissues, but the staining was weaker in primary and metastatic PCas (both P < 0.001, t-test). Furthermore, the low expression levels of KISS1 in PCas correlated with clinical stage (P < 0.01) and with KISS1R expression (P < 0.001). Overexpression of full-length KISS1 in low KISS1-expressing PC-3M cells, but not KFMΔSS, which lacks the secretion signal sequence, induced re-sensitization of cells to anoikis, although it had no effect on either cell proliferation or apoptosis. Overexpression of KISS1 also suppressed steps in the metastatic cascade, including motility and invasiveness. Moreover, cells overexpressing KISS1 were found to enhance chemosensitivity to paclitaxel. Collectively, our data suggest that KISS1 functions as a metastasis suppressor in PCas and may serve as a useful biomarker as well as a therapeutic target for aggressive PCas. PMID:22226740

  1. Clinical and biological significance of KISS1 expression in prostate cancer.

    PubMed

    Wang, Honghe; Jones, Jacqueline; Turner, Timothy; He, Qinghua P; Hardy, Shana; Grizzle, William E; Welch, Danny R; Yates, Clayton

    2012-03-01

    For men in the United States, prostate cancer (PCa) is the most frequent malignancy and the second leading cause of cancer mortality. The metastatic spread of PCa is responsible for most deaths related to PCa. Although KISS1 functions as a metastasis suppressor in various cancers, its expression levels and functions in PCa development and progression remain undetermined. The goals of this study were to correlate the expression levels of KISS1 in PCas with clinicopathologic characteristics and to assess the biological relevance of KISS1 to the viability and motility of PCa cells. Strong KISS1 staining was detected in benign prostate tissues, but the staining was weaker in primary and metastatic PCas (both P < 0.001, t-test). Furthermore, the low expression levels of KISS1 in PCas correlated with clinical stage (P < 0.01) and with KISS1R expression (P < 0.001). Overexpression of full-length KISS1 in low KISS1-expressing PC-3M cells, but not KFMΔSS, which lacks the secretion signal sequence, induced re-sensitization of cells to anoikis, although it had no effect on either cell proliferation or apoptosis. Overexpression of KISS1 also suppressed steps in the metastatic cascade, including motility and invasiveness. Moreover, cells overexpressing KISS1 were found to enhance chemosensitivity to paclitaxel. Collectively, our data suggest that KISS1 functions as a metastasis suppressor in PCas and may serve as a useful biomarker as well as a therapeutic target for aggressive PCas.

  2. Dormant Circulating Tumor Cells in Prostate Cancer: Therapeutic, Clinical and Biological Implications.

    PubMed

    Alvarez-Cubero, Maria J; Vázquez-Alonso, Fernando; Puche-Sanz, Ignacio; Ortega, F Gabriel; Martin-Prieto, M; Garcia-Puche, José L; Pascual-Geler, Manrique; Lorente, José A; Cozar-Olmo, José M; Serrano, Maria J

    2016-01-01

    Circulating Tumor Cells (CTCs) are a valuable prognostic factor in several solid tumors. By understanding the biological characteristics of CTCs we could better understand the biology of metastasis. CTCs usually adopt a dormant state that is believed to be a strategy to survive in extreme conditions. To enter a dormant state, CTCs undergo numerous phenotypic, genetic and functional mutations that significantly affect the efficacy of the therapies used to kill dormant CTCs. Hence, understanding the biological events involved in the dormancy process of CTCs would allow the identification of new therapeutic targets. Some experimental studies or preclinical models have explored these biological events, as well as the molecular factors that contribute to the maintenance of and release from dormancy. However, few studies have assessed the effects of anticancer therapies on dormant cells. This study reviews current the data currently available on cell dormancy mechanisms in prostate cancer, with a special focus on the functional, genetic and phenotypic plasticity of CTCs and their potential implications in the clinical and therapeutic management of prostate cancer.

  3. Results from a multicenter prostate IMRT dosimetry intercomparison for an OCOG-TROG clinical trial

    SciTech Connect

    Healy, B.; Frantzis, J.; Murry, R.; Martin, J.; Plank, A.; Middleton, M.; Catton, C.; Kron, T.

    2013-07-15

    Purpose: A multi-institution dosimetry intercomparison has been undertaken of prostate intensity modulated radiation therapy (IMRT) delivery. The dosimetry intercomparison was incorporated into the quality assurance for site credentialing for the Trans-Tasman Radiation Oncology Group Prostate Fractionated Irradiation Trial 08.01 clinical trial.Methods: An anthropomorphic pelvic phantom with realistic anatomy was used along with multiplanar dosimetry tools for the assessment. Nineteen centers across Australia and New Zealand participated in the study.Results: In comparing planned versus measured dose to the target at the isocenter within the phantom, all centers were able to achieve a total delivered dose within 3% of planned dose. In multiplanar analysis with radiochromic film using the gamma analysis method to compare delivered and planned dose, pass rates for a 5%/3 mm criterion were better than 90% for a coronal slice through the isocenter. Pass rates for an off-axis coronal slice were also better than 90% except for one instance with 84% pass rate.Conclusions: Strengths of the dosimetry assessment procedure included the true anthropomorphic nature of the phantom used, the involvement of an expert from the reference center in carrying out the assessment at every site, and the ability of the assessment to detect and resolve dosimetry discrepancies.

  4. Architectural heterogeneity and cribriform pattern predict adverse clinical outcome for Gleason grade 4 prostatic adenocarcinoma.

    PubMed

    Dong, Fei; Yang, Ping; Wang, Chaofu; Wu, Shulin; Xiao, Yu; McDougal, W Scott; Young, Robert H; Wu, Chin-Lee

    2013-12-01

    Gleason grade 4 defines a group of prostatic adenocarcinomas with a variety of architectural patterns, including poorly formed glands, fused glands, and cribriform pattern. To address the relative contribution to clinical prognosis by these distinct patterns, the histology of 241 consecutive radical prostatectomy specimens with the highest Gleason grade of 4 was reviewed. The presence of poorly formed glands, fused glands, and cribriform pattern was recorded for each case, and the types of architectural patterns present were associated with patient outcome. In this population, prostatic adenocarcinomas demonstrated architectural heterogeneity, with 17% of cases exhibiting a single Gleason grade 4 pattern, and 41% of cases exhibiting all 3 morphologic patterns. Patients exhibiting all 3 architectural patterns had lower rates of biochemical disease-free survival (66% vs. 76% at 5 y; log rank P=0.006). Twenty-two of 165 patients (13.3%) with cribriform pattern adenocarcinoma developed metastasis, whereas 2 of 76 patients (2.6%) without cribriform pattern developed metastasis at a median postoperative follow-up of 10.0 years. The presence of a cribriform pattern was an independent predictor for biochemical recurrence (hazard ratio 2.41; 95% confidence interval, 1.34-4.32; P=0.003) as well as metastasis after radical prostatectomy (hazard ratio 5.62; 95% confidence interval, 1.29-24.5; P=0.02). These results suggest that the morphologic subclassification of distinct Gleason grade 4 architectural patterns provides prognostic information beyond the current Gleason classification system.

  5. Kallikrein-related peptidases in prostate, breast, and ovarian cancers: from pathobiology to clinical relevance.

    PubMed

    Avgeris, Margaritis; Mavridis, Konstantinos; Scorilas, Andreas

    2012-04-01

    Tissue kallikrein (KLK1) and kallikrein-related peptidases (KLK2-15) comprise a family of 15 highly conserved secreted serine proteases with similar structural characteristics and a wide spectrum of functional properties. Both gene expression and protein activity of KLKs are rigorously controlled at various levels via diverse mechanisms, including extensive steroid hormone regulation, to exert their broad physiological role. Nevertheless, deregulated expression, secretion, and function of KLK family members has been observed in several pathological conditions and, particularly, in endocrine-related human malignancies, including those of the prostate, breast, and ovary. The cancer-related abnormal activity of KLKs upon substrates such as growth factors, cell adhesion molecules, cell surface receptors, and extracellular matrix proteins facilitate both tumorigenesis and disease progression to the advanced stages. The well-documented relationship between KLK status and the clinical outcome of cancer patients has led to their identification as promising diagnostic, prognostic, and treatment response monitoring biomarkers for these complex disease entities. The main objective of this review is to summarize the existing knowledge concerning the role of KLKs in prostate, breast, and ovarian cancers and to highlight their continually evolving biomarker capabilities that can provide significant benefits for the management of cancer patients.

  6. Androgen Receptor and Prostate Cancer Stem Cells: Biological Mechanisms and Clinical Implications

    PubMed Central

    Deng, Qu; Tang, Dean G.

    2015-01-01

    Prostate cancer (PCa) contains phenotypically and functionally distinct cells, and this cellular heterogeneity poses clinical challenges as the distinct cell types likely respond differently to various therapies. Clonal evolution, driven by genetic instability, and intra-clonal cancer cell diversification, driven by cancer stem cell (CSCs), together, create tumor cell heterogeneity. In this review, we first discuss prostate cancer stem cells (PCSCs) and heterogeneity of androgen receptor (AR) expression in primary, metastatic and treatment-failed PCa. Based on literature reports and our own studies, we hypothesize that whereas PCSCs in primary and untreated tumors and models are mainly AR−, PCSCs in CRPCs could be either AR+ or AR−/lo. We illustrate the potential mechanisms whereby AR+ and AR− PCSCs may employ to propagate PCa at the population level, mediate therapy resistance, and metastasize. As a result, targeting AR alone may not be able to achieve long-lasting therapeutic efficacy. Elucidating the roles of AR and PCSCs should provide important clues to designing novel personalized combinatorial therapeutic protocols targeting both AR+ and AR− PCa cells. PMID:26285606

  7. A comparative study of seed localization and dose calculation on pre- and post-implantation ultrasound and CT images for low-dose-rate prostate brachytherapy

    NASA Astrophysics Data System (ADS)

    Ali, Imad; Algan, Ozer; Thompson, Spencer; Sindhwani, Puneet; Herman, Terence; Cheng, Chih-Yao; Ahmad, Salahuddin

    2009-09-01

    This work investigates variation in the volume of the prostate measured at different stages through the prostate brachytherapy procedure for 30 patients treated with I-125 radioactive seeds. The implanted seeds were localized on post-implantation ultrasound (US) images and the effect of prostate enlargement due to edema on dose coverage for 15 patients was studied. The volume of the prostate was measured at four stages as follows: (a) 2-3 weeks prior to implantation using US imaging, (b) then at the start of the intra-operative prostate brachytherapy procedure on the day of the implant, (c) immediately post-implantation using US imaging in the operating room and (d) finally by CT imaging at nearly 4 weeks post-implantation. Comparative prostate volume studies were performed using US imaging stepper and twister modes. For the purpose of this study, the implanted seeds were localized successfully on post-implant ultrasound twister images, retrospectively. The plans using post-implant US imaging were compared with intra-operative plans on US and plans created on CT images. The prostate volume increases about 10 cm3 on average due to edema induced by needle insertion and seed loading during implantation. The visibility of the implanted seeds on US twister images acquired post-implantation is as good as those on CT images and can be localized and used for dose calculation. The dose coverage represented by parameters such as D90 (dose covering 90% of the volume) and V100 (volume covered by 100% dose) is poorer on plans performed on post-implantation twister US studies than on the intra-operative live plan or the CT scan performed 4 weeks post-operatively. For example, the mean D90 difference on post-implantation US is lower by more than 15% than that on pre-implantation US. The volume enlargement of the prostate due to edema induced by needle insertion and seed placement has a significant effect on the quality of dosimetric coverage in brachytherapy prostate seed

  8. Therapeutic substitutions in the midst of new technology diffusion: The case of treatment for localized prostate cancer.

    PubMed

    Shen, Chan; Tina Shih, Ya-Chen

    2016-02-01

    Robotic surgical systems have become increasingly popular worldwide. Robotic assisted radical prostatectomies have been widely adopted in the treatment of localized prostate cancer, replacing the conventional open surgeries. However, it is not clear whether this was achieved by substitution within the same treatment type (i.e., replacing open surgeries with robotic-assisted surgeries) or substitution across treatment types (i.e., expanding the proportion of patients receiving surgery while crowding out other forms of treatment for localized prostate cancer). Given the large number of patients undergoing these procedures each year, it is important to study the impact of the fast diffusion of robotic surgical systems on the overall treatment pattern of localized prostate cancer. We addressed this question using state-level cancer epidemiology data (256 observations) extracted from 2002 to 2010 National Cancer Database, and supply-side variables (e.g. density of robotic surgical systems, urologists) obtained from Area Resource File as well as investor presentations posted at the website of the manufacturer of robotic surgical systems. Recognizing that the purchase decision of robotic systems is potentially endogenous, we used an optimal instrumental variables panel estimation method to examine the impact while taking into account of the panel structure and the potential endogeneity of the density of robotic surgical systems and its quadratic term. We found that the density of robotic systems at state-level had a significantly positive impact on the rate of surgery and a significantly negative impact on the rate of radiation therapy. Further, our age-stratified analysis showed that the increase in surgery rate was most pronounced in the younger population. In conclusion, our findings suggest that part of the increase in the rate of surgery was driven by substitution across treatment types with a large proportion originating from the younger population.

  9. 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

  10. 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

  11. 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

  12. Prostate cancer: comparison of local staging accuracy of pelvic phased-array coil alone versus integrated endorectal-pelvic phased-array coils. Local staging accuracy of prostate cancer using endorectal coil MR imaging.

    PubMed

    Fütterer, Jurgen J; Engelbrecht, Marc R; Jager, Gerrit J; Hartman, Robert P; King, Bernard F; Hulsbergen-Van de Kaa, Christina A; Witjes, J Alfred; Barentsz, Jelle O

    2007-04-01

    To compare the visibility of anatomical details and prostate cancer local staging performance of pelvic phased-array coil and integrated endorectal-pelvic phased-array coil MR imaging, with histologic analysis serving as the reference standard. MR imaging was performed in 81 consecutive patients with biopsy-proved prostate cancer, prior to radical prostatectomy, on a 1.5T scanner. T2-weighted fast spin echo images of the prostate were obtained using phased-array coil and endorectal-pelvic phased-array coils. Prospectively, one radiologist, retrospectively, two radiologists and two less experienced radiologists working in consensus, evaluated and scored all endorectal-pelvic phased-array imaging, with regard to visibility of anatomical details and local staging. Receiver operator characteristics (ROC) analysis was performed. Anatomical details of the overall prostate were significantly better evaluated using the endorectal-pelvic phased-array coil setup (P<0.05). The overall local staging accuracy, sensitivity and specificity for the pelvic phased-array coil was 59% (48/81), 56% (20/36) and 62% (28/45), and for the endorectal-pelvic phased-array coils 83% (67/81), 64% (23/36) and 98% (44/45) respectively, for the prospective reader. Accuracy and specificity were significantly better with endorectal-pelvic phased-array coils (P<0.05). The overall staging accuracy, sensitivity and specificity for the retrospective readers were 78-79% (P<0.05), 56-58% and 96%, for the endorectal-pelvic phased-array coils. Area under the ROC curve (Az) was significantly higher for endorectal-pelvic phased-array coils (Az=0.74) compared to pelvic phased-array coil (Az=0.57), for the prospective reader. The use of endorectal-pelvic phased array coils resulted in significant improvement of anatomic details, extracapsular extension accuracy and specificity. Overstaging is reduced significantly with equal sensitivity when an endorectal-pelvic phased-array coil is used.

  13. Biomarkers for Early Detection of Clinically Relvant Prostate Cancer: A Multi-Institutional Validation Trial - Genomic Health, Inc. — EDRN Public Portal

    Cancer.gov

    Validate a panel of tissue-based biomarkers to determine the presence of or progression to clinically relevant prostate cancer at the time of diagnosis. Utilize a novel, biopsy based multi-gene quantitative RT-PCR assay developed by Genomic Health, Oncotype DX Prostate Cancer Assay, which discriminates aggressive from indolent cancer on multivariate modeling of PCa patients.

  14. Clinical potential of gene-directed enzyme prodrug therapy to improve radiation therapy in prostate cancer patients.

    PubMed

    Vajda, Alice; Marignol, Laure; Foley, Ruth; Lynch, Thomas H; Lawler, Mark; Hollywood, Donal

    2011-12-01

    Despite the advances in prostate cancer diagnosis and treatment, current therapies are not curative in a significant proportion of patients. Gene-directed enzyme prodrug therapy (GDEPT), when combined with radiation therapy, could improve the outcome of treatment for prostate cancer, the second l