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Introduction: This study aims to determine if there is a difference in prostate cancer nomogram-adjusted risk of biochemical recurrence (BCR) and/or adverse pathology (AP) between African American (AAM) and Caucasian men (CM) undergoing radical prostatectomy (RP)., Methods: A retrospective review was performed of men undergoing RP in the Pennsylvania Urologic Regional Collaborative between 2015 and 2021. Cox proportional hazard regression models were used to compare the rate of BCR after RP, and logistic regression models were used to compare rates of AP after RP between CM and AAM, adjusting for the CAPRA, CAPRA-S, and MSKCC pre- and post-operative nomogram scores., Results: Rates of BCR and AP after RP were analyzed from 3190 and 5029 men meeting inclusion criteria, respectively. The 2-year BCR-free survival was lower in AAM (72.5%) compared to CM (79.0%), with a hazard ratio (HR) of 1.38 (95% CI 1.16-1.63, p < 0.001). The rate of BCR was significantly greater in AAM compared to CM after adjustment for MSKCC pre-op (HR 1.29; 95% CI 1.08-1.53; p = 0.004), and post-op nomograms (HR 1.26; 95% CI 1.05-1.49; p < 0.001). There was a trend toward higher BCR rates among AAM after adjustment for CAPRA (HR 1.13; 95% CI 0.95-1.35; p = 0.17) and CAPRA-S nomograms (HR 1.11; 95% 0.93-1.32; p = 0.25), which did not reach statistical significance. The rate of AP was significantly greater in AAM compared to CM after adjusting for CAPRA (OR 1.28; 95% CI 1.10-1.50; p = 0.001) and MSKCC nomograms (OR 1.23; 95% CI 1.06-1.43; p = 0.007)., Conclusion: This analysis of a large multicenter cohort provides further evidence that AAM may have higher rates of BCR and AP after RP than is predicted by CAPRA and MSKCC nomograms. Accordingly, AAM may benefit with closer post-operative surveillance and may be more likely to require salvage therapies., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Multiparametric magnetic resonance imaging (mpMRI) has been increasingly utilized in prostate cancer (CaP) diagnosis and staging. While Level 1 data supports MRI utility in CaP diagnosis, there is less data on staging utility. We sought to evaluate the real-world accuracy of mpMRI in staging localized CaP., Materials and Methods: Men who underwent radical prostatectomy (RP) for CaP in 2021 at our institution were identified. Sensitivity, specificity, positive predictive value and negative predictive value of mpMRI in predicting pT2N0 organ confined disease , extracapsular extension , seminal vesicle invasion , lymph node involvement, and bladder neck invasion were evaluated. Associations between MRI accuracy and AUA risk stratification (AUA RS), MRI institution (MRI-I), MRI strength (1.5 vs. 3T) (MRI-S), and MRI timing (MRI-T) were assessed. These analyses were repeated using Pennsylvania Urologic Regional Collaborative (PURC) data., Results: Institutional and community mpMRI CaP staging data demonstrated poor sensitivity (2.9%-49.2%% vs. 16.8%-24.4%), positive predictive value (40%-100% vs. 35.8%-68.2%), and negative predictive value (56.3%-94.3% vs. 68.4%-96.2%) in predicting surgical pathologic features - in contrast, specificity (89.1%-100% vs. 93.9%-98.6%) was adequate. mpMRI accuracy for extracapsular extension, seminal vesicle invasion, and lymph node involvement was significantly (p < 0.001) associated with AUA RS. There was no association between mpMRI accuracy and MRI-I, MRI-S, and MRI-T., Conclusion: Despite enthusiasm for its use, in a real-world setting, mpMRI appears to be a poor staging study for localized CaP and is unreliable as the sole means of staging patients prior to prostatectomy. mpMRI should be used cautiously as a staging tool for CaP, and should be interpreted considering individual patient risk strata., Competing Interests: Declaration of Competing Interests All authors of this manuscript have directly participated in planning, execution, and/or analysis of this study. The contents of this manuscript have not been copyrighted or published previously. The contents of this manuscript are not now under consideration for publication elsewhere. The contents of this manuscript will not be copyrighted, submitted, or published elsewhere while acceptance by Urologic Oncology: Seminars and Original Investigations is under consideration. There are no directly related manuscripts or abstracts, published or unpublished, by any authors of this manuscript. No financial support or incentive has been provided for this manuscript., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Prostate MRI detecting PI-RADs = 3 lesions has low diagnostic utility for prostate malignancy. Use of PSA density has been suggested to further risk-stratify these men, to potentially avoid biopsies in favor of monitoring. We evaluate the ability of PSA density (PSAd) to risk-stratify PIRADs 3 lesions across patients who underwent a prostate biopsy in a large multi-institutional collaborative., Materials and Methods: Pennsylvania Urology Regional Collaborative (PURC) is a voluntary quality improvement collaborative of 11 academic and community urology practices in Pennsylvania and New Jersey. A retrospective analysis was performed on all patients in the PURC database that had a prostate MRI with PI-RADs 3 lesions only. PSA just before the MRI and prostate size reported on MRI were used to calculate the PSA. Clinicopathologic data were evaluated. Univariable analysis using Chi-Square and Kruskal Wallis tests and multivariable logistic regression were used to identify predictors of any PCa, and clinically significant prostate cancer (csPCa) was defined as ≥ Grade Group 2 (GG2.) RESULTS: Between May 2015 and March 2021, 349 patients with PIRADs 3 lesions only were identified and comprised the cohort of interest. Median PSA was 5.0 with a prostate volume of 58cc and a median PSA density of 0.11, 10.6% of the cohort was African American with 81.4% being Caucasian. Significant prostate cancer was detected in 70/349 (20.0%) men. Smaller prostate volume, abnormal DRE, and higher PSAd were significantly associated with clinically significant prostate cancer on univariable analysis. In men with PSAd <0.15, 31/228 (13.6%) harbored csPCa. Multivariable analysis confirmed that men with PSAd >0.15 were more likely to harbor clinically significant prostate cancer (P < 0.001)., Conclusion: Across a large regional collaborative, patients with PIRADs 3 lesions on mpMRI were noted to have clinically significant cancer in 20% of biopsies. Using a PSA density cut-off of 0.15 may result in missing clinically significant prostate cancer in 13.6%. This information is useful for prebiopsy risk stratification and counseling., Competing Interests: Declaration of Competing Interest X All authors of this manuscript have directly participated in planning, execution, and/or analysis of this study (if not, specify)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction and Objective: In 2018, the U.S. Food and Drug Administration approved the da Vinci single-port (SP) system, in which four instruments are still utilized, but enter through a single-site access trocar. Herein, we report the largest case series for SP robot-assisted radical prostatectomy (RARP) to date. Our primary aim is to analyze the perioperative and short-term outcomes of this procedure. Our secondary aim is an assessment of the learning curve with this new platform. Methods: A total of 157 patients underwent SP RARP by two surgeons who have completed >3000 multiport robotic surgeries collectively. Institutional Review Board-approved prospectively collected data were used. Basic demographic preoperative variables and perioperative outcomes were analyzed. Results: Median patient age and prostate-specific antigen was 63 years and 6.3 ng/mL before treatment (interquartile range [IQR] 4.7-8.2 ng/mL). Average prostate weight was 47 g. The median operating time was 195 minutes (IQR 165-221.25 minutes) with a median estimated blood loss of 100 mL (IQR 100-200 mL). Surgeon 1's operating time stabilized around case #56, and Surgeon 2 around case #26. Surgeon 2 used the transperitoneal approach for the first 7 cases. There were no intraoperative complications. There were six total postoperative complications (3.8%) and four (2.5%) were Clavien-Dindo scale ≥IIIa. One hundred ten patients went home same day, 45 stayed 1 night at the hospital, with only 2 patients requiring stay in the hospital for more than 1 night (70%, 29%, and 1% respectively). With the median follow-up period of 9 months, rates of biochemical recurrence, pad-free, and potency preservation were 8.3%, 82.5%, and 64.4%, respectively. Conclusions: This case series confirms the safety and efficacy of SP RARP with acceptable short-term outcomes. There is a significant learning curve for this new modality. Shorter hospital stay appears to be an early benefit of the SP platform.

Background: To investigate the effects of the U.S. Preventive Services Task Force's (USPSTF) 2012 recommendation against prostate-specific antigen (PSA)-based screening for prostate cancer on survival disparities based on insurance status. Prior to the USPSTF's 2012 screening recommendation, previous studies found that insured patients with prostate cancer had better outcomes than uninsured patients., Methods: Using the SEER 18 database, we examined prostate cancer-specific survival (PCSS) based on diagnostic time period and insurance status. Patients were designated as belonging to the pre-USPSTF era if diagnosed in 2010-2012 or post-USPSTF era if diagnosed in 2014-2016. PCSS was measured with the Kaplan-Meier method, while disparities were measured with the Cox proportional hazards model., Results: During the pre-USPSTF era, uninsured patients experienced worse PCSS compared to insured patients (adjusted HR 1.256, 95% CI 1.037-1.520, p = 0.020). This survival disparity was no longer observed during the post-USPSTF era as a result of decreased PCSS among insured patients combined with unchanged PCSS among uninsured patients (adjusted HR 0.946, 95% CI 0.642-1.394, p = 0.780)., Conclusions: Although the underlying reasons are not clear, the USPSTF's 2012 PSA screening recommendation may have hindered insured patients from being regularly screened for prostate cancer and selectively led to worse outcomes for insured patients without affecting the survival of uninsured patients., (© 2022. The Author(s).)

Since 2004, multiple blockbuster drugs have been approved for men with metastatic prostate cancer. Nevertheless, it has been reported that no improvement in survival was observed between 2004 and 2009. Herein, we have analyzed the SEER database to assess the survival outcome of metastatic prostate cancer patients since 2000. The results demonstrated that there was an improvement in both overall and prostate cancer-specific survival for 4 months among men diagnosed with metastatic prostate cancer from 2010 to 2016 when compared to those in the pre-2010 period. Interestingly, this survival benefit was limited to patients with bone and visceral metastasis (M1b and M1c stages). Collectively, our observation suggests that despite the new treatment agents such as second-line antiandrogen therapies introduced in the modern era, the improvement in survival of metastatic prostate cancer patients has been surprisingly small., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Importance: Early in the COVID-19 pandemic, racial/ethnic minority communities disproportionately experienced poor outcomes; however, the association of the pandemic with prostate cancer (PCa) care is unknown., Objective: To assess the association between race and PCa care delivery for Black and White patients during the first wave of the COVID-19 pandemic., Design, Setting, and Participants: This multicenter, regional, collaborative, retrospective cohort study compared prostatectomy rates between Black and White patients with untreated nonmetastatic PCa during the COVID-19 pandemic (269 patients from March 16 to May 15, 2020) and prior (378 patients from March 11 to May 10, 2019)., Main Outcomes and Measures: Prostatectomy rates., Results: Of the 647 men with nonmetastatic PCa, 172 (26.6%) were non-Hispanic Black men, and 475 (73.4%) were non-Hispanic White men. Black men were significantly less likely to undergo prostatectomy during the pandemic compared with White patients (1 of 76 [1.3%] vs 50 of 193 [25.9%]; P < .001), despite similar COVID-19 risk factors, biopsy Gleason grade groups, and comparable prostatectomy rates prior to the pandemic (17 of 96 [17.7%] vs 54 of 282 [19.1%]; P = .75). Black men had higher median prostate-specific antigen levels prior to biopsy (8.8 ng/mL [interquartile range, 5.3-15.2 ng/mL] vs 7.2 ng/mL [interquartile range, 5.1-11.1 ng/mL]; P = .04). A linear combination of regression coefficients with an interaction term for year demonstrated an odds ratio for likelihood of surgery of 0.06 (95% CI, 0.01-0.35; P = .002) for Black patients and 1.41 (95% CI, 0.81-2.44; P = .23) for White patients during the pandemic compared with prior to the pandemic. Changes in surgical volume varied by site (from a 33% increase to complete shutdown), with sites that experienced the largest reduction in cancer surgery caring for a greater proportion of Black patients., Conclusions and Relevance: In this large multi-institutional regional collaborative cohort study, the odds of PCa surgery were lower among Black patients compared with White patients during the initial wave of the COVID-19 pandemic. Although localized PCa does not require immediate treatment, the lessons from this study suggest systemic inequities within health care and are likely applicable across medical specialties. Public health efforts are needed to fully recognize the unintended consequence of diversion of cancer resources to the COVID-19 pandemic to develop balanced mitigation strategies as viral rates continue to fluctuate.

Introduction: Magnetic resonance imaging (MRI)-ultrasound fusion targeted prostate biopsy (FB) has been advocated by many experts as a replacement for the standard template biopsy. Herein, we compared pathology results and cancer detection rates of FB with our standard 14-core systematic prostate biopsy (SB) that includes 2 anterior cores., Materials and Methods: One hundred two men with elevated prostate-specific antigen and suspicious lesions on multiparametric MRI, Prostate Imaging Reporting And Data System (PI-RADS) v2 score ≥ 3, underwent FB. Each target lesion was biopsied 3 times; our SB was performed concurrently. Biopsy results were compared for overall and clinically significant (cs), defined as Gleason score ≥ 7, cancer detection., Results: Fifty-two percent of patients had positive biopsy results, and of those, 44 had cs prostate cancer (PCa). The overall detection rates for FB and SB were 39% and 50%, respectively, and there was no statistical difference in the detection rate of csPCa detection rate (P = .42). Of 17 patients diagnosed with a high-risk PCa, defined as Gleason score ≥ 8, SB identified 15, whereas FB identified 10. Within the SB group, 21 had positive anterior core biopsies, of which 11 were cs., Conclusion: Expanding the standard template prostate biopsies to include 2 anterior horn sampling may be just as effective as FB in men with PI-RADS lesion ≥ 3, thereby mitigating the increased cost associated with FB., (Copyright © 2020. Published by Elsevier Inc.)

Background: In May 2012, the US Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA)-based screening for prostate cancer (PCa), assigning it a grade D. This decision then was modified in 2018 to a grade C for men aged 55 to 69 years. The authors hypothesized that changes in screening practices would reduce survival outcomes for both Black and White men but maintain racial discrepancies in outcomes., Methods: Using the Surveillance, Epidemiology, and End Results database, the authors examined PCa-specific survival based on race and year of diagnosis. The period between January 2010 and December 2012 was categorized as the pre-USPSTF era, whereas the period between January 2014 and December 2016 was classified as the post-USPSTF era. The year 2013 was considered the transition year and was excluded from the analysis., Results: A total of 49,388 men were identified in the pre-USPSTF era who were diagnosed with PCa, approximately 83.7% of whom were White and 16.3% of whom were Black. In the post-USPSTF era, a total of 41,829 men were diagnosed with PCa, approximately 82.7% of whom were White and 17.3% of whom were Black. When compared with the pre-USPSTF era, men diagnosed in the post-USPSTF era were found to have more adverse clinical features. In the pre-USPSTF era, White men were less likely to die of PCa than Black men. This survival disparity between White and Black men was no longer observed in the post-USPSTF era., Conclusions: In men diagnosed with PCa between 2014 and 2016, a survival disparity between White and Black men was not observed due to a decrease in survival among White men while the survival of Black men remained steady., (© 2020 American Cancer Society.)

Purpose: National Comprehensive Cancer Network (NCCN) guidelines recommend confirmatory biopsy within 12 months of active surveillance (AS) enrollment. With <10 cores on initial biopsy, re-biopsy should occur within 6 months. Our objective was to determine if patients on AS within practices in the Pennsylvania Urologic Regional Collaborative (PURC) receive guideline concordant confirmatory biopsies., Materials and Methods: Within PURC, a prospective collaborative of diverse urology practices in Pennsylvania and New Jersey, we identified men enrolled in AS after first biopsy, analyzing time to re-biopsy and factors associated with various intervals of re-biopsy., Results: In total, 1,047 patients were enrolled in AS for a minimum of 12 months after initial biopsy. Four hundred seventy-seven (45%) underwent second biopsy at 1 of the 9 PURC practices. The number of patients undergoing re-biopsy within 6 months, 6 to 12 months, 12 to 18 months, and >18 months was 71 (14%), 218 (45.7%), 134 (28%), and 54 (11%), respectively. Sixty percent underwent confirmatory biopsy within 12 months. On multivariate analysis, re-biopsy interval was associated with number of positive cores, perineural invasion, and practice ID (all P < 0.05). Adjusted multivariable regression did not identify factors predictive of re-biopsy interval., Conclusion: Of patients who underwent confirmatory biopsy at PURC practices, 60.5% were within 12 months per NCCN guidelines. This suggests area for improvement in guideline adherence after enrollment in AS. All practices that offer AS should periodically perform similar analyses to monitor their performance. In an era of value-based care, adherence to guideline based active surveillance practices may eventually comprise national quality metrics affecting provider reimbursement., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Men with locally advanced prostate cancer (LAPCa) or regionally advanced prostate cancer (RAPCa) are at high risk for death from their disease. Clinical guidelines support multimodal approaches, which include radical prostatectomy (RP) followed by radiotherapy (XRT) and XRT plus androgen deprivation therapy (ADT). However, there are limited data comparing these substantially different treatment approaches. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, this study compared survival outcomes and adverse effects associated with RP plus XRT versus XRT plus ADT in these men., Methods: SEER-Medicare data were queried for men with cT3-T4N0M0 (LAPCa) or cT3-T4N1M0 (RAPCa) prostate cancer. Propensity score methods were used to balance cohort characteristics between the treatment arms. Survival analyses were analyzed with the Kaplan-Meier method and Cox proportional hazards models., Results: From 1992 to 2009, 13,856 men (≥65 years old) were diagnosed with LAPCa or RAPCa: 6.1% received RP plus XRT, and 23.6% received XRT plus ADT. At a median follow-up of 14.6 years, there were 2189 deaths in the cohort, of which 702 were secondary to prostate cancer. Regardless of the tumor stage or the Gleason score, the adjusted 10-year prostate cancer-specific survival and 10-year overall survival favored men who underwent RP plus XRT over men who underwent XRT plus ADT. However, RP plus XRT versus XRT plus ADT was associated with higher rates of erectile dysfunction (28% vs 20%; P = .0212) and urinary incontinence (49% vs 19%; P < .001)., Conclusions: Men with LAPCa or RAPCa treated initially with RP plus XRT had a lower risk of prostate cancer-specific death and improved overall survival in comparison with those men treated with XRT plus ADT, but they experienced higher rates of erectile dysfunction and urinary incontinence., (© 2018 American Cancer Society.)

Introduction: Pelvic lymph node dissection (PLND) is not recommended for low-risk prostate cancer (PCa) patients. However, the rate of PLND in this population is unknown., Methods: We queried the National Cancer Data Base for PCa patients who underwent robot-assisted radical prostatectomy from 2010 to 2013 and stratified them by D'Amico risk classification. We identified the frequency of PLND in low-risk patients and identified factors associated with receipt of PLND. Further, we determined the number of lymph nodes evaluated (quality) and proportion of patients with detected nodal metastatic disease (utility) in each risk group., Results: Of 51,971 patients with low-risk PCa who underwent robot-assisted radical prostatectomy, 19,059 (36.7%) received PLND. Predictors of PLND in low-risk patients included rural residence (odds ratio [OR], 1.157; 95% confidence interval [CI], 1.009-1.327), treatment at an academic center (OR, 1.492; 95% CI 1.188-1.874), and high-volume facility (OR, 1.327; 95% CI, 1.078-1.633). The mean number of lymph nodes obtained in low-risk patients was lower than in intermediate/high-risk patients (4.74 vs. 5.86, P < .0001). Lymph node positivity was identified in 0.4% of low-risk patients and 4.6% of intermediate/high-risk patients., Conclusion: While PLND is not recommended for low-risk PCa by clinical practice guidelines, it was performed frequently (36.7%) in a large hospital-based data set. PLND in this population was of lower quality (nodal yield) and had less utility of detecting nodal metastatic disease than PLND in intermediate/high-risk PCa. Treatment at a high-volume or academic center was associated with increased use of PLND. Reasons for the variation in practice patterns should be investigated to improve the value of PCa care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Medical therapy has undergone many changes as our understanding of prostate cancer cell biology has improved. Androgen deprivation therapy (ADT) remains the mainstay of therapy for metastatic disease. Metastatic castrate-resistant prostate cancer (CRPC) is an important concern since we are unable to stop progression with currently available agents. Areas covered: Pharmacologic ADT is the most commonly used treatment for metastatic prostate cancer. Multiple agents are available for both first-line and second-line use: antiandrogens, estrogens, luteinizing hormone-releasing hormone agonists/antagonists, and CYP17 inhibitors. With adoption of these drugs, it is important to consider their pharmacokinetic and pharmacodynamic properties. Many undergo metabolism through cytochrome P450. Levels may be altered with co-administration of drugs acting as enzyme inhibitors or inducers. Understanding mechanism of action, metabolism, and excretion of these drugs allows clinicians to provide the best therapeutic care while minimizing adverse events. Expert opinion: Many men with metastatic prostate cancer will progress to castration resistance. An understanding of resistance mechanisms at the cellular level has revealed new drug targets with hopes of halting or reversing progression of metastatic disease. Second-line agents, traditionally reserved for CRPC, are being studied in metastatic castrate-sensitive prostate cancer, and may offer practice-changing evidence supporting their use.

Background: Renal cell carcinoma (RCC) is one of the most lethal genitourinary cancers. The presence of androgen receptor (AR) in RCC has recently been shown to be associated with higher tumour stage irrespective of gender. Because the clinical context of androgens in female RCC patients is similar to that of prostate cancer patients undergoing androgen-deprivation therapy, mechanisms underlying the emergence of castration-resistant prostate cancer (CRPC) may be at play in AR-positive RCC cells. Therefore, we hypothesized that AR-positive RCC has intratumoral steroidogenesis and that anti-androgen therapy may result in tumour suppression., Methods: Mice were injected with an AR-positive RCC cell line. When tumours became palpable, surgical castration was performed and tumour volume was measured. Using ELISA, the levels of intracellular testosterone and dihydrotesterone were measured in AR-positive human RCC cell lines. Lastly, male mice containing xenografts were treated with enzalutamide or abiraterone acetate (AA) for 3 weeks to measure tumour volume., Results: We first observed in vivo that castration retards the growth of AR-positive RCC tumour xenograft in mice. Next, AR-positive human RCC cell lines and tissues were found to have elevated levels of testosterone and dihydrotestosterone and express key enzymes required for intracellular androgen biosynthesis. A mouse xenograft study with AR-positive RCC cell line using the commonly used anti-androgen therapies showed significant tumour suppression (P<0.01)., Conclusions: Intracrine androgen biosynthesis is a potential source of androgen in AR-positive RCC and that the androgen signaling axis is a potential target of intervention in RCC.

Introduction: The purpose of the study was to evaluate the cost differences between robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP) in various census regions of the United States because RARP has been reported to be more expensive than ORP with significant regional cost variations in radical prostatectomy (RP) cost across the United States., Patients and Methods: International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients with prostate cancer who underwent RARP or ORP from the Nationwide Inpatient Sample (NIS) database from 2009 to 2011. Hospital costs were compared using the Wilcoxon rank sum test and multivariable linear regression analysis adjusting for age, sex, race, comorbidities, and hospital characteristics., Results: From the NIS database, 24,636 RARP and 13,590 ORP procedures were identified and evaluated. The lowest cost overall was in the South; the highest cost RARP was in the West and for ORP in the Northeast. In multivariable analysis, adjusted according to patient and hospital characteristics, RARP was 43.3% more costly in the Midwest, 37.2% more costly in the South, and 39.1% more costly in the West (P < .0001 for all). In contrast, the cost for RARP in the Northeast was 12.8% less than for ORP (P < .0001)., Conclusion: Cost for RP significantly varies within the nation and in most regions it is significantly greater for RARP than for ORP. ORP in the Northeast is more costly than RARP. Further research is needed to delineate the reason for these differences and to optimize the cost of RP., (Published by Elsevier Inc.)

Purpose: Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management., Materials and Methods: Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes., Results: The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes., Conclusions: The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Prostate cancer (PCa) remains the second ranked cause of cancer deaths in the United States. The current standard of care for metastatic prostate cancer (mPCa) includes systemic therapies with no option for surgery. In contrast, in other malignancies such as breast and kidney cancer, cyto-reduction plays an integral role in the treatment of metastatic disease. In this framework, there are emerging data that suggest a potential oncologic benefit to cytoreduction in mPCa. The majority of the data are retrospective in nature suggesting that patients with mPCa who had prior radical prostatectomy (RP) had a better survival, as well as improved response to systemic therapy. Similarly, patients who presented with metastatic disease and received definitive local therapy (RP or radiation) had greater survival than patients who received no treatment. In order to confer maximum potential benefit, operating in the setting of mPCa must be technically feasible with acceptable morbidity. It has been demonstrated in many studies that operating on locally advanced disease (T3a/b) does have similar morbidity as lower stage cancer. This may be applicable in the metastatic setting, because although PCa may have metastasized, it may remain locally advanced. On the molecular level there are a number of explanations concerning the potential benefit of cytoreduction. However, these ideas remain speculative with no concrete evidence to date.

Background: Biomarkers predicting tumor response are important to emerging targeted therapeutics. Complimentary methods to assess and understand genetic changes and heterogeneity within only few cancer cells in tissue will be a valuable addition for assessment of tumors such as prostate cancer that often have insufficient tumor for next generation sequencing in a single biopsy core., Methods: Using confocal microscopy to identify cell-to-cell relationships in situ, we studied the most common gene rearrangement in prostate cancer (TMPRSS2 and ERG) and the tumor suppressor CHD1 in 56 patients who underwent radical prostatectomy., Results: Wild type ERG was found in 22 of 56 patients; ERG copy number was increased in 10/56, and ERG rearrangements confirmed in 24/56 patients. In 24 patients with ERG rearrangements, the mechanisms of rearrangement were heterogeneous, with deletion in 14/24, a split event in 7/24, and both deletions and split events in the same tumor focus in 3/24 patients. Overall, 14/45 (31.1%) of patients had CHD1 deletion, with the majority of patients with CHD1 deletions (13/14) correlating with ERG-rearrangement negative status (P < 0.001)., Conclusions: These results demonstrate the ability of confocal microscopy and FISH to identify the cell-to-cell differences in common gene fusions such as TMPRSS2-ERG that may arise independently within the same tumor focus. These data support the need to study complimentary approaches to assess genetic changes that may stratify therapy based on predicted sensitivities., (© 2014 Wiley Periodicals, Inc.)

Objective: To investigate the impact of prostate-specific antigen density (PSAD) on existing prostate cancer (PCa) active surveillance (AS) protocols., Methods: Prospectively maintained database on men with PCa who underwent radical prostatectomy was reviewed retrospectively. Demographic data and pathologic characteristics of patients who fulfilled the AS inclusion criteria under the National Comprehensive Cancer Network (NCCN), Prostate Cancer Research International Active Surveillance (PRIAS), and University of California, San Francisco (UCSF) guidelines were examined., Results: Of 930 patients, 231, 280, and 325 fulfilled the NCCN, PRIAS, and UCSF AS criteria, respectively. The frequencies of advanced disease on surgical pathology (upstaging and/or upgrading) were 31.6% (NCCN), 35.4% (PRIAS), and 34.2% (UCSF) of the study cohorts. PSAD was significantly higher in patients with advanced disease compared with that in patients with nonadvanced disease in all 3 AS schemas. Modifying the PRIAS and UCSF criteria using the NCCN's lower PSAD cutoff of 0.15 ng/mL(2) decreased the rates of the advanced disease significantly to 33.5% and 31.4%, respectively. Using the receiver operating characteristic curve analysis, the optimal PSAD cutoff level for the prediction of advanced disease was 0.085 ng/mL(2) (sensitivity/specificity of 76.7%/50.6% in NCCN and 75.6%/49.7% in PRIAS)., Conclusion: Among patients with low-risk PCa who underwent radical prostatectomy, PSAD is a predictor of advanced disease at the time of surgery. Adopting a lower PSAD threshold of 0.085 ng/mL(2) decreased the risk of the advanced disease to 17.5%-21.7%. Therefore, PSAD should be part of all AS guidelines., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To compare the clinicopathologic findings of African-American (AA) and White-American (WA) men with prostate cancer (PCa) who were candidates for active surveillance (AS) and underwent radical prostatectomy (RP)., Methods: Prospectively maintained database of men who underwent RP from 2 academic centers were analyzed retrospectively. Postoperative pathologic characteristics of patients who met the AS inclusion criteria of the University of California, San Francisco (UCSF) and National Comprehensive Cancer Network (NCCN) were evaluated. After RP, the rate of pathological upstaging and Gleason upgrading were compared between AA and WA men., Results: In the AA cohort, 196 and 124 men met the UCSF and NCCN criteria for AS, respectively. With respect to WA patients, 191 and 148 fulfilled the AS criteria for UCSF and NCCN, respectively. AA men had a higher percentage of maximum biopsy core than WA men (15.3%-20.4% vs 11.5%-15.0%, P <.05, respectively) in both cohorts. In addition, a greater proportion of AA men had multiple positive biopsy cores compared to WA men (45.2% vs 33.1%, P = .046) under the NCCN criteria. A higher proportion of AA men were upstaged (≥pT3) compared to WA men (19.4% vs 10.1%, P = .037). A multivariate regression test revealed that age, preoperative PSA, and number of positive cores were independent predictors of more advanced disease (upstaging and/or upgrading) in AA men., Conclusion: AA men who were candidates for AS criteria had worse clinicopathological features on final surgical pathology than WA men. These results suggest that a more stringent AS criteria should be considered in AA men with prostate cancer., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Prostate cancer (CaP) continues to be a significant burden on men's health. While significant advances have been made in the diagnosis and treatment of localized disease, androgen deprivation therapy remains the treatment of choice for advanced and metastatic disease. However, once a man progresses on androgen deprivation, therapies targeting castration-resistant CaP have been extremely limited until quite recently. Urologic oncologists who wish to play an active role in the treatment of men with CaP from diagnosis through end-of-life care should be familiar with administration of and toxicities associated with chemotherapeutic agents. This review is directed at urologists and urologic oncologists and will discuss many of the FDA-approved intravenous agents currently available for castration-resistant CaP with a specific focus on the side-effects associated with these regimens., (Published by Elsevier Inc.)

Purpose of Review: This article reviews recent developments in the use of active surveillance for localized prostate cancer., Recent Findings: The treatment of localized prostate cancer continues to be a major challenge for urologic oncologists. Screening with prostate-specific antigen has resulted in increased numbers of low-risk prostate cancers being detected. Aggressive whole-gland therapy with surgery, or radiation therapy is associated with potentially life-altering treatment-related side effects such as urinary incontinence, bowel toxicity and erectile dysfunction. The goal of active surveillance is to avoid or delay the adverse events associated with prostate cancer therapy while still allowing for curative intervention in the future, if needed., Summary: Active surveillance is a reasonable treatment option for many men with low-risk, and some men with intermediate-risk, prostate cancer. Additional research is needed to determine the optimal active surveillance inclusion criteria, monitoring schedule, and treatment triggers. It is hoped that advances in prostate imaging, biomarkers, and focal therapy will foster greater use of active surveillance in appropriately selected men to optimize quality-of-life without compromising cancer outcomes.

Despite the high frequency with which radical prostatectomy is used to treat prostate cancer, uncertainty exists regarding the merits of a simultaneous pelvic lymph node dissection. Unresolved issues include identifying the optimal candidate and selecting the appropriate surgical template, among others. In this article, the authors discuss the pros and cons of performing a pelvic lymph node dissection and the staging/diagnostic and therapeutic implications of this procedure. The lack of robust randomized clinical trials in the literature necessitates a careful analysis of retrospective and case series data., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Androgen deprivation therapy (ADT) has been the cornerstone of treatment for advanced prostate cancer for over 65 years. Although there can be worrisome side effects, data will be presented that for men with metastatic prostate cancer, immediate ADT can reduce the likelihood of developing the rare but catastrophic sequellae of metastatic disease, although it is unlikely to prolong survival compared with waiting for symptoms before initiating ADT. Additionally, for patients with extremely high risk prostate cancer that is not distantly metastatic (e.g. have a life expectancy from prostate cancer less than 10 years with all other available treatments except immediate ADT) and, whose life expectancy from non-prostate cancer diseases is excellent during this period, early ADT both alone and in conjunction with definitive local treatment prolongs survival. Moreover, ADT seems to be most effective when the cancer volume is low. However, eventually most men receiving ADT experience disease progression. The biological mechanisms explaining how prostate cancer escapes from ADT's control include: 1) Alterations in the androgen receptor (AR) and in the AR co-factors (which modify the responsiveness of the AR to androgens) allow molecules and medications which are not normally AR agonists to act as agonists. 2) The human prostate gland, and particularly prostate cancer, may be able to synthesize androgens from both cholesterol and adrenal androgens. This may occur because prostate cancer tissue has higher concentrations of androgens than does the serum in patients receiving ADT. Thus, castrated men may not be starving their prostate cancers of androgens. 3) The AR in prostatic stroma far more strongly stimulates both malignant and benign prostatic epithelial growth than the epithelial AR does. Indeed, the epithelial AR, particularly in advanced prostate cancer, may have anti-proliferative and anti-tumor progression properties. That is, the AR in the prostatic epithelial cells, particularly malignant ones, may act as a tumor suppressor. Thus, by inhibiting the epithelial AR, its protective effects may be abrogated. The controversial nature of these concepts, as well as the clinical and experimental data which support and question them, will be presented. Additionally, strategies for addressing each of these escape mechanisms, which may be able to prolong responsiveness to ADT, will be discussed.

Androgen deprivation continues to play a crucial role in the treatment of advanced and metastatic prostate cancer. In the 65 years since its use was first described, urologists and medical oncologists have developed new and innovative ways to manipulate the hypothalamic-pituitary-gonadal axis with the goal of alleviating symptoms and prolonging the life of men with prostate cancer. Despite the successes that androgen deprivation therapy has brought, each method and regimen possesses unique benefits and burdens, of which the clinician and patient must be cognizant. This review discusses the first-line androgen deprivation methods and regimens presently in use with special attention paid to their side effects and the management of them, as well as the question of when to initiate androgen deprivation therapy.

PurposeGleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management.Materials and methodsMembers of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes.ResultsThe Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes.ConclusionsThe definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

Purpose: Our aim was to prospectively evaluate the diagnostic accuracy of sentinel lymph node biopsy-guided lymph node dissection compared to extended pelvic lymph node dissection in patients with intermediate- or high-risk prostate cancer. Materials and Methods: We conducted a prospective, single-arm, multicenter study at 3 tertiary centers in France between February 2012 and May 2019. Eligible patients had clinically localized intermediate- or high-risk prostate cancer. After intraprostatic injection of (99m)Tc-nanocolloid, the locations of the sentinel lymph nodes were defined by preoperative lymphoscintigraphy. Surgical excision of the sentinel lymph nodes was performed using intraoperative gamma probe guidance. After resection of the sentinel lymph nodes, extended pelvic lymph node dissection was performed in all patients. We assessed the diagnostic accuracy of the sentinel lymph node biopsy method using extended pelvic lymph node dissection as the reference standard. This trial was registered in ClinicalTrials.gov (NCT02732392). Results: A total of 162 men cN0M0 (CT scan and bone scan) were enrolled: 106 (65.4%) and 56 (34.6%) patients had intermediate- and high-risk prostate cancer, respectively. The median number of nodes retrieved was 14 (mean 16, IQR 10-21) per patient. At final pathological analysis, 22 patients (13.6%) were pN+. Sensitivity, specificity, negative predictive value, and positive predictive value of sentinel lymph node biopsy method in detecting patients with at least 1 lymph node metastasis were 95.4% (95% CI, 75.1-99.7), 100% (95% CI, 96.6-100), 99.2% (95% CI, 95.5-99.9), and 100% (95% CI, 80.7-100), respectively. Conclusions: Our multicenter prospective study supports that sentinel lymph node biopsy is a very effective and sensitive method for pelvic lymph node staging in patients with intermediate- or high-risk localized prostate cancer. [ABSTRACT FROM AUTHOR]