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Background: The aim of this study was to describe pathologic and short-term oncologic outcomes among Black and White men with grade group 4 or 5 prostate cancer managed primarily by radical prostatectomy., Methods: This was a multi-institutional, observational study (2005-2015) evaluating radical prostatectomy outcomes by self-identified race. Descriptive analysis was performed via nonparametric statistical testing to compare baseline clinicopathologic data. Univariable and multivariable time-to-event analyses were performed to assess biochemical recurrence (BCR), metastasis, cancer-specific mortality (CSM), and overall survival between Black and White men., Results: In total, 1662 men were identified with grade group 4 or 5 prostate cancer initially managed by radical prostatectomy. Black men represented 11.3% of the cohort (n = 188). Black men were younger, demonstrated a longer time from diagnosis to surgery, and were at a lower clinical stage (all P < .05). Black men had lower rates of pT3/4 disease (49.5% vs 63.5%; P < .05) but higher rates of positive surgical margins (31.6% vs 26.5%; P = .14) on pathologic evaluation. There was no difference in BCR, CSM, or overall survival over a median follow-up of 40.7 months. Black men had a lower 5-year cumulative incidence of metastasis-free survival (93.6%; 95% confidence interval [CI], 86.5%-97.0%) in comparison with White men (85.8%; 95% CI, 83.1%-88.0%), which did not persist in an age-adjusted analysis., Conclusions: Black and White men with high-grade prostate cancer at diagnosis demonstrated similar oncologic outcomes when they were managed by primary radical prostatectomy. Our findings suggest that racial disparities in prostate cancer mortality are not related to differences in the efficacy of extirpative therapy., (© 2021 American Cancer Society.)

High-risk prostate cancer is a heterogeneous disease that lacks clear consensus on its ideal management. Historically, non-surgical treatment was the preferred strategy, and several studies demonstrated improved survival among men with high-risk disease managed with the combination of radiotherapy and androgen deprivation therapy (ADT) compared with ADT alone. However, practice trends in the past 10-15 years have shown increased use of radical prostatectomy with pelvic lymph node dissection for primary management of high-risk, localized disease. Radical prostatectomy, as a primary monotherapy, offers the potential benefits of avoiding ADT, reducing rates of symptomatic local recurrence, enabling full pathological tumour staging and potentially reducing late adverse effects such as secondary malignancy compared with radiation therapy. Retrospective studies have reported wide variability in short-term (pathological) and long-term (oncological) outcomes of radical prostatectomy. Surgical monotherapy continues to be appropriate for selected patients, whereas in others the best treatment strategy probably involves a multimodal approach. Appropriate risk stratification utilizing clinical, pathological and potentially also genomic risk data is imperative in the initial management of men with prostate cancer. However, data from ongoing and planned prospective trials are needed to identify the optimal management strategy for men with high-risk, localized prostate cancer.

Purpose: We examined rates of Grade Group 4 downgrading at radical prostatectomy among men diagnosed with high and very high risk prostate cancer at biopsy., Materials and Methods: A pooled cohort of 1,776 patients from 3 tertiary referral centers who underwent radical prostatectomy for National Comprehensive Cancer Network® high risk (prostate specific antigen greater than 20 ng/ml, or Grade Group 4-5, or clinical stage T3 or greater) or very high risk (primary Gleason pattern 5, or more than 4 biopsy cores with Grade Group 4-5, or 2 or more high risk features) disease from 2005 to 2015 were reviewed. Overall 893 patients with Grade Group 4 disease at biopsy were identified and 726 patients were available for analysis. Multivariable logistic regression models were fit to determine factors associated with downgrading to Grade Group 3 or less at radical prostatectomy., Results: Overall 333 (45%) cases were downgraded to Grade Group 3 or less at radical prostatectomy. Of these cases 198 (27%) had concordant Grade Group 4 biopsy and radical prostatectomy pathology and 195 (27%) were upgraded at radical prostatectomy to Grade Group 5. Of high risk cases with biopsy Grade Group 4 disease 49% had any downgrading vs 29% of very high risk cases (p <0.0001). Downgrading to Grade Group 2 or less occurred in 16% (98 of 604) of high risk and 7% (8 of 122) of very high risk cases (p <0.01). Downgraded cases had a lower prostate specific antigen, fewer positive biopsy cores and lower clinical stage (p <0.01). On multivariable analysis fewer positive biopsy cores were significantly associated with downgrading at radical prostatectomy (p <0.01)., Conclusions: In this cohort of patients with high risk/very high risk prostate cancer, downgrading from biopsy Grade Group 4 at radical prostatectomy occurred less frequently than in other published reports. Any downgrading was significantly less common in very high risk compared to high risk patients, and downgrading to Grade Group 2 or less occurred in a minority of cases in high risk and very high risk patients.

Background: The optimal treatment for unfavorable intermediate-risk prostate cancer is unknown. Given the lack of randomized evidence, large comparative studies may be useful in guiding clinical decision-making., Methods: We queried the National Cancer Database for patients with unfavorable intermediate-risk prostate cancer, as defined by the National Comprehensive Cancer Network. We compared overall survival between patients treated with radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy, and EBRT plus brachytherapy (EBRT+BT) using Cox proportional hazards models and propensity score matching., Results: A total of 10,439 patients were analyzed. There was no statistically significant difference in overall survival between RP and EBRT+BT (hazard ratio [HR] = 1.24; 95% confidence interval [CI] 0.58-2.65). RP was associated with higher survival when compared to EBRT (HR = 2.30, 95% CI 1.70-3.20) and brachytherapy (HR = 2.90, 95% CI 1.40-6.20). When accounting for androgen deprivation therapy (ADT), there was no statistically significant difference in survival between RP and brachytherapy with ADT (HR = 3.08; 95% CI 0.62-15.27) or EBRT to a dose of ≥7920 cGy with ADT (HR = 2.6, 95% CI 0.50-13.20)., Conclusion: We found no statistically significant difference in survival between RP and EBRT+BT. EBRT and brachytherapy had higher mortality, respectively, compared to RP. When including only radiotherapy patients who received ADT and, in the case of EBRT, a total dose ≥ 7920 cGy, there was no statistically significant difference in survival when comparing RP to EBRT or brachytherapy. These findings should be prospectively studied., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Among men with localized high-risk prostate cancer (PCa), patients who meet very high-risk (VHR) criteria have been shown to experience worse outcomes after radical prostatectomy (RP) in a previous study. Variations of VHR criteria have been suggested to be prognostic in other single-center cohorts, but multicenter outcomes validating VHR criteria have not been described. This study was designed to validate VHR criteria for identifying which PCa patients are at greatest risk for cancer progression., Methods: Patients with high-risk PCa undergoing RP (2005-2015) at 3 tertiary centers were pooled. The outcomes of men with VHR PCa were compared with the outcomes of those who did not meet VHR criteria. The high-risk criteria were a clinical stage of T3 to T4, a prostate-specific antigen level > 20 ng/mL, or a biopsy Gleason grade sum of 8 to 10. The VHR criteria were multiple high-risk features, >4 biopsy cores with a Gleason grade sum of 8 to 10, or primary Gleason grade pattern 5. Biochemical recurrence, metastasis (METS), and cancer-specific mortality (CSM) were assessed with competing risks regressions. Overall mortality was assessed with Cox survival models., Results: Among 1981 patients with high-risk PCa, men with VHR PCa (n = 602) had adverse pathologic outcomes: 37% versus 25% for positive margins and 37% versus 15% for positive lymph nodes (P <  .001 for both comparisons). Patients with VHR PCa also had higher adjusted hazard ratios for METS (2.78; 95% confidence interval [CI], 2.08-3.72), CSM (6.77; 95% CI, 2.91-15.7), and overall mortality (2.44; 95% CI, 1.56-3.80; P <  .001 for all comparisons)., Conclusions: In a validation study of patients who underwent treatment for high-risk PCa, VHR criteria were strongly associated with adverse pathologic and oncologic outcomes., (© 2018 American Cancer Society.)

Background: Certain patients presenting with either low or very-low-risk prostate cancer (PCa) can represent a therapeutic dilemma for physicians. The oncologic outcomes of active surveillance (AS) for men with very-low-risk PCa are overall excellent. However, there are concerns about AS related to the potential for upgrading or upstaging. The African American (AA) population is under-represented in studies evaluating AS outcomes and this is particularly important because of the unique epidemiology of PCa in AA men., Methods: A literature review through the Medline database published from 1990 until August 2015 was performed to identify studies reporting outcomes of the AA population with low-risk PCa that underwent either AS or treatment. An additional search for studies on genetic mechanisms involved in development of PCa in AA men was also performed., Results: Eleven studies on pathologic results of AA men who would qualify for AS were identified and in eight of these studies AA race was found to be associated with adverse pathological outcomes such as positive surgical margins, upgrading or upstaging. The other three studies reported no significance in these parameters with respect to race. Five more studies reported outcomes of AS in AA men with different study end points. AA men were mainly found to have a higher rate of disease reclassification subsequent to active treatment. The studies on genetic mechanisms also identified different genetic alterations in the AA population., Conclusions: AA men with clinically defined low-risk PCa may have either a higher grade or volume of cancer that was not detected on routine evaluation. Therefore, AS among such patients should be approached with caution. We recommend discussing such risks with AA patients with an acknowledgement that existing favorable outcomes noted in largely Caucasian populations may not be applicable to AA patients. We propose a modified evaluation plan for AA patients that includes an early confirmatory biopsy preceded by an magnetic resonance imaging to optimally detect occult cancer foci.

Background: It remains unclear whether men selecting active surveillance (AS) are at increased risk of unfavorable longer term outcomes as compared with men who undergo immediate treatment., Objective: To compare adverse pathologic outcomes in men with favorable-risk prostate cancer who underwent delayed prostatectomy after surveillance (DPAS) to those who elected immediate prostatectomy (IRP)., Design, Setting, and Participants: We conducted a retrospective analysis of a prospective AS registry from 2004 to 2014. From the Johns Hopkins AS program (n = 1298), we identified a subset of men who underwent DPAS (n = 89) and was representative of the entire cohort, not just those that were reclassified to higher risk. These men were compared with men who underwent IRP (n = 3788)., Outcome Measurements and Statistical Analysis: We measured adverse pathologic features (primary Gleason pattern ≥ 4, seminal vesicle invasion [SVI], or lymph node [LN] positivity). Multivariable models were adjusted for age, prostate-specific antigen density, and baseline risk classification., Results and Limitations: Delayed prostatectomy occurred at a median of 2.0 yr (range: 0.6-9.0) after diagnosis. The DPAS and IRP cohorts demonstrated similar proportions of men with primary Gleason pattern ≥ 4 (17% vs 20%; p = 0.11), SVI (3.3% vs 3.2%; p = 0.53), LN positivity (2.3% vs 1.2%; p = 0.37), and overall adverse pathologic features (21.3% vs 17.0%; p = 0.32). The adjusted odds ratio of adverse pathology was 1.33 (95% confidence interval, 0.82-2.79; p = 0.13) for DPAS as compared with IRP. Limitations include a modest cohort size and a limited number of events., Conclusions: In men with favorable-risk cancer, the decision to undergo AS is not independently associated with adverse pathologic outcomes., Patient Summary: This report compares men with favorable-risk prostate cancer who elected active surveillance with those who underwent immediate surgery accounting for evidence that approximately one-third of men who choose surveillance will eventually undergo treatment. Our findings suggest that men who are closely followed with surveillance may have similar outcomes to men who elect immediate surgery, but additional research is needed., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To report race-based outcomes after radical prostatectomy (RP) in a cohort stratified by National Comprehensive Cancer Network (NCCN) risk category with updated follow-up., Materials and Methods: Studies describing racial disparities in outcomes after RP are conflicting. We studied 15,993 white and 1634 African American (AA) pretreatment-naïve men who underwent RP at our institution (1992-2013) with complete preoperative and pathologic data. Pathologic outcomes were compared between races using appropriate statistical tests; biochemical recurrence (BCR) for men with complete follow-up was compared using multivariate models that controlled separately for preoperative and postoperative covariates., Results: Very low- and low-risk AA men were more likely to have positive surgical margins (P <.01), adverse pathologic features (P <.01), and be upgraded at RP (P <.01). With a median follow-up of 4.0 years after RP, AA race was an independent predictor of BCR among NCCN low-risk (HR, 2.16; P <.001) and intermediate-risk (hazard ratio [HR], 1.34; P = .024) classes and pathologic Gleason score ≤ 6 (HR, 2.42; P <.001) and Gleason score 7 (HR, 1.71; P <.001). BCR-free survival for very low-risk AA men was similar to low-risk white men (P = .890); BCR-free survival for low-risk AA men was similar to intermediate-risk white men (P = .060)., Conclusion: When stratified by NCCN risk, AA men with very low-, low-, or intermediate-risk prostate cancer who undergo RP are more likely to have adverse pathologic findings and BCR compared with white men. AA men with "low risk" prostate cancer, especially those considering active surveillance, should be counseled that their recurrence risks can resemble those of whites in higher risk categories., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Men destined to have early biochemical recurrence (BCR) following radical prostatectomy (RP) may be optimal candidates for multimodal treatment. Here we identified pre-operative predictors of early BCR within a surgical cohort who recurred., Methods: An institutional prostate cancer (PCa) database containing over 20,000 patients was queried to identify 1,471 men who had BCR after RP, and pre-operative predictors of early versus late BCR were assessed. Early BCR was defined as recurrence within 1 year after RP. Within the recurrence cohort, those with National Comprehensive Cancer Network (NCCN) high-risk features were more likely to experience early BCR. Therefore, in all NCCN high-risk men in the database, we abstracted detailed pathologic biopsy data. Among 753 high-risk men, 41 alternate multivariable criteria were assessed for their ability to predict early BCR in crude and adjusted logistic regression models., Results: The criteria that best identified those likely to experience early BCR are primary Gleason pattern 5 on biopsy or ≥4 cores containing pattern 4 (odds ratio 3.17, P < 0.001). These criteria included 26.7% of NCCN high-risk men. Additionally, these criteria selected for men within the high-risk classification who were at significantly higher risk of subsequent metastasis (adjusted hazard ratio 3.04, P < 0.001) and cancer-specific death (adjusted hazard ratio 3.27, P < 0.001)., Conclusions: In men with PCa who present with high-risk features, pre-operative criteria have the ability to discriminate the subgroup most likely to experience early BCR after RP. Men at risk for early disease recurrence may be the most suitable candidates for multimodal therapy., (© 2014 Wiley Periodicals, Inc.)

Objective: To evaluate the operative and pathologic outcomes of laparoscopic radical prostatectomy and robot-assisted radical prostatectomy in men with progressive changes in body mass index (BMI) category., Materials and Methods: A single-surgeon series of 1023 laparoscopic radical prostatectomy and robot-assisted radical prostatectomy (mostly extraperitoneal) patients was considered. Of these patients, 987 were evaluable. Results were stratified by the World Health Organization BMI category. Multivariate linear and logistic regression analysis was used to model the operating time, length of stay, positive surgical margins, and noncurable cancer., Results: Of the 987 patients, 563 (57%) were overweight and 193 (19.6%) were obese. Of the 193 obese patients, 152 (15.4%) had a BMI of 30 to <35 kg/m(2) (class I obesity), 28 (2.8%) a BMI of 35 to <40 kg/m(2) (class II), and 13 (1.3%) a BMI of ≥40 kg/m(2) (class III). No differences were found in the estimated blood loss, complications, PSM, pathologic stage, or biochemical recurrence across the BMI categories (6-month median follow-up). However, pelvic lymph node dissection was more commonly omitted and the nerve-sparing score was inferior in the obese men. On multivariate analysis, a higher BMI was a significant predictor of a longer operating time., Conclusion: Obese men can safely undergo laparoscopic radical prostatectomy or robot-assisted radical prostatectomy, although the ability to perform excellent nerve sparing appears to decrease with increasing obesity. Nevertheless, obese men can expect perioperative and early oncologic outcomes comparable to those of normal weight men without an increased risk of perioperative complications., (Copyright © 2013 Elsevier Inc. All rights reserved.)