Organoid cultures derived from patients with advanced prostate cancer.

The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D organoid system, we report success in long-term culture of prostate cancer from biopsy specimens and circulating tumor cells. The first seven fully characterized organoid lines recapitulate the molecular diversity of prostate cancer subtypes, including TMPRSS2-ERG fusion, SPOP mutation, SPINK1 overexpression, and CHD1 loss. Whole-exome sequencing shows a low mutational burden, consistent with genomics studies, but with mutations in FOXA1 and PIK3R1, as well as in DNA repair and chromatin modifier pathways that have been reported in advanced disease. Loss of p53 and RB tumor suppressor pathway function are the most common feature shared across the organoid lines. The methodology described here should enable the generation of a large repertoire of patient-derived prostate cancer lines amenable to genetic and pharmacologic studies.

Have urinary function outcomes after radical prostatectomy improved over the past decade?

BACKGROUND: Changes in surgical technique and postoperative care that target improvements in functional outcomes are widespread in the literature. Radical prostatectomy (RP) is one such procedure that has seen multiple advances over the past decade. The objective of this study was to leverage RP as an index case to determine whether practice changes over time produced observable improvements in patient-reported outcomes. METHODS: This study analyzed patients undergoing RP by experienced surgeons at a tertiary care center with prospectively maintained patient-reported outcome data from 2008 to 2019. Four patient-reported urinary function outcomes at 6 and 12 months after RP were defined with a validated instrument: good urinary function (domain score ≥ 17), no incontinence (0 pads per day), social continence (≤1 pad per day), and severe incontinence (≥3 pads per day). Multivariable logistic regressions evaluated changes in outcomes based on the surgical date. RESULTS: Among 3945 patients meeting the inclusion criteria, excellent urinary outcomes were reported throughout the decade but without consistent observable improvements over time. Specifically, there were no improvements in good urinary function at 12 months (P = .087) based on the surgical date, and there were countervailing effects on no incontinence (worsening; P = .005) versus severe incontinence (improving; P = .003). Neither approach (open, laparoscopic, or robotic), nor nerve sparing, nor membranous urethral length mediated changes in outcomes. CONCLUSIONS: In a decade with multiple advances in surgical and postoperative care, there was evidence of improvements in severe incontinence, but no measurable improvements across 3 other urinary outcomes. Although worsening disease factors could contribute to the stable observed outcomes, a more systematic approach to evaluating techniques and implementing patient selection and postoperative care advances is needed. LAY SUMMARY: Although there have been advances in radical prostatectomy over the past decade, consistent observable improvements in postoperative incontinence were not reported by patients. To improve urinary function outcomes beyond the current high standard, the approach to studying innovations in surgical technique needs to be changed, and further development of other aspects of prostatectomy care is needed.

Prevalence of High-Risk Prostate Cancer Metastasis to Cloquet's Ilioinguinal Lymph Node.

PURPOSE: Cloquet's node, located at the junction between the deep inguinal nodes and the external iliac chain, is easily accessible and commonly excised during pelvic lymph node dissection for prostate cancer. However, we hypothesize that Cloquet's node is not part of lymphatic metastatic spread of prostate cancer. MATERIALS AND METHODS: Between September 2016 and June 2019, 105 consecutive patients with high-risk prostate cancer (cT3a or Grade Group 4/5, or prostate specific antigen >20 ng/ml) underwent a laparoscopic radical prostatectomy and pelvic lymph node dissection. First, Cloquet's node was identified, retrieved and submitted separately to pathology as right and left Cloquet's node. Next, a pelvic lymph node dissection was completed including the external iliac, obturator fossa and hypogastric nodal packets. Each lymph node was cut into 3 mm slices which were separately embedded in paraffin, stained with hematoxylin and eosin, and examined microscopically. RESULTS: The final analysis included 95 patients. In this high-risk population, the median number of nodes removed was 22 (IQR 18-29); 39/95 patients (41%) had lymph node metastasis. The median number of Cloquet's nodes removed was 2 (IQR 2-3). Cloquet's node was negative in all but 1 patient (1.1%), who had very high-risk features and high metastatic burden in the lymph nodes. CONCLUSIONS: In high-risk prostate cancer, metastasis to the ilioinguinal node of Cloquet is rare. Given this low prevalence, Cloquet's node can be safely excluded from the pelvic lymph node dissection template.

Oncologic Outcomes of Total Length Gleason Pattern 4 on Biopsy in Men with Grade Group 2 Prostate Cancer.

PURPOSE: Gleason Score 7 prostate cancer comprises a wide spectrum of disease risk, and precise substratification is paramount. Our group previously demonstrated that the total length of Gleason pattern (GP) 4 is a better predictor than %GP4 for adverse pathological outcomes at radical prostatectomy. We aimed to determine the association of GP4 length on prostate biopsy with post-prostatectomy oncologic outcomes. MATERIALS AND METHODS: We compared 4 GP4 quantification methods-including maximum %GP4 in any single core, overall %GP4, total length GP4 (mm) across all cores and length GP4 (mm) in the highest volume core-for prediction of biochemical recurrence-free survival after radical prostatectomy using multivariable Cox proportional hazards regression. RESULTS: A total of 457 men with grade group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy. The 3-year biochemical recurrence-free survival probability was 85% (95% CI 81-88). On multivariable analysis, all 4 GP4 quantification methods were associated with biochemical recurrence-maximum %GP4 (HR=1.30; 95% CI 1.07-1.59; p=0.009), overall %GP4 (HR=1.61; 95% CI 1.21-2.15; p=0.001), total length GP4 (HR=2.48; 95% CI 1.36-4.52; p=0.003) and length GP4 in highest core (HR=1.32; 95% CI 1.11-1.57; p=0.001). However, we were unable to identify differences between methods of quantification with a relatively low event rate. CONCLUSIONS: These findings support further studies on GP4 quantification in addition to the ratio of GP3 and GP4 to classify prostate cancer risk. Research should also be conducted on whether GP4 quantification could provide a surrogate endpoint for disease progression for trials in active surveillance.

Characterization of Symptoms after Radical Prostatectomy and Their Relation to Postoperative Complications.

PURPOSE: Many patients will experience symptoms in the initial days after radical prostatectomy (RP), but early patient-reported symptoms have not been well characterized. Our objective was to illustrate the pattern of symptoms experienced after RP and the relation of severe symptoms to postoperative complications. MATERIALS AND METHODS: In 2016, electronic patient-reported symptom monitoring began at our institution's ambulatory surgery center. We retrospectively reviewed patients treated with minimally invasive RP who were sent a daily questionnaire completed using a web interface until postoperative day 10. Severe symptoms automatically generate a "yellow alert," which messages the clinic, while very severe symptoms generate a "red alert," additionally prompting the patient to call. We summarized rates of moderate-to-very severe symptoms and fit local polynomial regressions. We compared rates of 30-day or 90-day complications (grade ≥2) based on the presence of alert symptoms. RESULTS: Of 2,266 men undergoing RP, 1,942 (86%) completed surveys. Among moderate-to-very severe symptom levels, pain (72%) and dyspnea (11%) were most common. Pain, nausea and dyspnea consistently decreased over time; fever and vomiting had a flat pattern. In patients experiencing red-alert symptoms, we observed a higher risk of 30-day complications, but rates were low and differences between groups were nonsignificant (2.9% vs 1.9%; difference 1.1%; 95% CI -1.3-3.5; p=0.3). Results were similar examining 90-day complications. CONCLUSIONS: While symptoms are common after RP, substantial improvements occur over the first 10 days. Severe or very severe symptoms conferred at most a small absolute increase in complication risk, which should be reassuring to patients and clinicians.

Morbidity of salvage radical prostatectomy: limited impact of the minimally invasive approach.

PURPOSE: We aimed to report the morbidity profile of salvage radical prostatectomy (SRP) after radiotherapy failure and assess the impact of minimally invasive surgery (MIS) on postoperative complications and functional outcomes. MATERIALS AND METHODS: Between 1985 and 2019, a total of 293 patients underwent SRP; 232 underwent open SRP; and 61 underwent laparoscopic SRP with or without robotic assistance. Complications were recorded and classified into standardized categories per the Clavien-Dindo classification. RESULTS: Twenty-nine patients (10%) experienced grade 3 complications within 30 days, 22 (9.5%) after open and 7 (11%) after MIS (p = 0.6). Between 30 and 90 days after surgery, 7.3% of patients in the open group and 10% in the MIS group had grade 3 complications (p = 0.5). The most common complication was bladder neck contracture (BNC), representing 40% of the 30-90 day complications. Within one year of SRP, 81 patients (31%, 95% CI 25%, 37%) developed BNC; we saw non-significant lower rates in MIS (25 vs 32%; p = 0.4). Functional outcomes were poor after SRP and showed no difference between open and MIS groups for urinary continence (16 vs 18%, p = 0.7) and erectile function (7 vs 13%, p = 0.4). 5 year cancer-specific survival and overall survival was 95% and 88% for the entire cohort, respectively. CONCLUSIONS: Our outcomes suggest poor functional recovery after SRP, regardless of the operative approach. Currently there is no evidence favoring the use of open or MIS approach. Further studies are required to ensure comparable outcomes between these approaches.

Extensive disease among potential candidates for hemi-ablative focal therapy for prostate cancer.

OBJECTIVE: To examine a set of proposed eligibility factors for hemi-ablative focal therapy in prostate cancer and to determine the likelihood of residual extensive disease. METHODS: We retrospectively analyzed data from 98 patients with unilateral prostate cancer on biopsy with detailed tumor maps from whole-mount slides and preoperative magnetic resonance imaging data. These patients met the focal therapy consensus meeting inclusion criteria (prostate-specific antigen <15 ng/mL, clinical stage T1c-T2a and Gleason score 3 + 3 or 3 + 4 on needle biopsy), and underwent radical prostatectomy between 2000 and 2014. Extensive disease was defined as having Gleason pattern 4/5 in bilateral lobes, any extraprostatic extension, seminal vesicle invasion or lymph node invasion. Both lobes of the prostate were scored on magnetic resonance imaging. Preoperative characteristics including biopsy and magnetic resonance imaging data were used to predict extensive disease. RESULTS: Among our cohort of 98 patients, 40% (95% CI 30-50%) had extensive disease. A total of 33% (95% CI 24-43%) had Gleason pattern 4/5 in both lobes with a median Gleason pattern 4/5 tumor volume in the biopsy negative lobe of 0.06 cm3 , 17 patients had pathological tumor stage ≥3 and one patient had lymph node invasion. CONCLUSIONS: An important number of patients meeting the focal therapy consensus meeting inclusion criteria can present extensive disease. Further studies using targeted biopsies might provide more accurate information about the selection of focal therapy candidates.

Biopsy Core Features are Poor Predictors of Adverse Pathology in Men with Grade Group 1 Prostate Cancer.

PURPOSE: Active surveillance is often restricted to patients with low risk prostate cancer who have 3 or fewer positive cores. We aimed to identify predictors of adverse pathology results for low risk prostate cancer treated with radical prostatectomy and determine whether a threshold number of positive cores could help the decision process for active surveillance. MATERIALS AND METHODS: A total of 3,359 men with low risk prostate cancer underwent radical prostatectomy between January 2000 and August 2016. We analyzed the relationship between biopsy core features and adverse pathology at radical prostatectomy, defined as Grade Group 3 or greater, seminal vesicle invasion or lymph node involvement. RESULTS: Of the 171 cases (5.1%) with adverse pathology findings at radical prostatectomy 144 (4.3%) were upgraded to Grade Group 3 or greater, 31 (0.9%) had seminal vesicle invasion and 15 (0.4%) had lymph node involvement. Prostate specific antigen and patient age were the only predictors of adverse pathology results. There was no significant association with the number of positive cores, the total mm of cancer or the maximum percent of cancer in any core. When we expanded the definition of adverse pathology to include Grade Group 2 and extraprostatic extension, the association between core features and outcome was statistically significant but clinically weak, and with no evidence of threshold effects. CONCLUSIONS: There is little basis for excluding patients with otherwise low risk prostate cancer on biopsy from active surveillance based on criteria such as the number of positive cores or the maximum cancer involvement of biopsy cores.

Does Subclassification of Pathologically Organ Confined (pT2) Prostate Cancer Provide Prognostic Discrimination of Outcomes after Radical Prostatectomy?

PURPOSE: We tested the latest update in the prostate cancer staging system by assessing the prognostic association of pT2 subclassification with the probability of survival related outcomes in patients who underwent radical prostatectomy. MATERIALS AND METHODS: We retrospectively analyzed the records of a total of 15,305 patients who underwent radical prostatectomy at 2 referral centers between 1985 and 2016, and had pT2 disease at the final pathological evaluation. Descriptive statistics were used to compare baseline data stratified by pT2 substages (pT2a/b vs pT2c). Cox regression models were adjusted for institution analyzed differences in the rate of biochemical recurrence, metastasis, cancer specific death and overall mortality. Multivariable Cox regression models were used to evaluate the predictive value of pT2 subclassification for survival, including the linear predictor from the Stephenson nomogram. RESULTS: Prostate specific antigen levels and Gleason score differed significantly between the pT2 substages (each p <0.0001). At a median followup of 6.0 years (IQR 3.3-10.1) 2,083 patients had biochemical recurrence, 161 had metastases, 43 had died of prostate cancer and 1,032 had died of another cause. On univariate analysis the pT2 subclassification was significantly associated with biochemical recurrence (p = 0.001) and distant metastasis (p = 0.033) but not with cancer specific death (p = 0.6) or overall mortality (p = 0.3). Multivariable analysis showed no evidence of a significant association between the pT2 subclassification and biochemical recurrence (p = 0.4) or distant metastasis (p = 0.6). Multivariable analysis of cancer specific death and overall mortality was omitted due to lack of significance on univariate analysis. CONCLUSIONS: Subclassification of pT2 prostate cancer is not a prognostic indicator of survival related outcomes after radical prostatectomy. Our results validate the elimination of pT2 substages in the updated staging system.

Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically.

PURPOSE: To assess the association between obstructive sleep apnea (OSA) and Fuhrman grade in patients with clear cell renal cell carcinoma (ccRCC). As secondary endpoints, we studied its association with tumor size, metastasis-free survival (MFS) and cancer-specific survival (CSS). METHODS: We reviewed the databases of two tertiary care centers, identifying 2579 patients who underwent partial or radical nephrectomy for ccRCC between 1991 and 2014. Descriptive statistics were used to compare pathologic variables between patients with and without OSA. Linear and logistic regression models were used to assess the association of OSA with Fuhrman grade and tumor size. A Cox proportional hazards model was used to determine OSA association with MFS and CSS. A pathway analysis was performed on a cohort with available gene expression data. RESULTS: In total, 172 patients (7 %) had self-reported OSA at diagnosis. More patients with OSA had high Fuhrman grade compared to those without OSA [51 vs. 38 %; 13 % risk difference; 95 % confidence interval (CI), 5-20 %; p = 0.003]. On multivariable analysis, the association remained significant (OR 1.41; 95 % CI 1.00-1.99; p = 0.048). OSA was not associated with tumor size (p > 0.5), MFS (p = 0.5) or CSS (p = 0.4). A trend toward vascular endothelial growth factor pathway enrichment was seen in OSA patients (p = 0.08). CONCLUSIONS: OSA is associated with high Fuhrman grade in patients undergoing surgery for ccRCC. Pending validation of this novel finding in further prospective studies, it could help shape future research to better understand etiological mechanisms associated.

Nephrometry scores and perioperative outcomes following robotic partial nephrectomy.

OBJECTIVES: Based on imaging features, nephrometry scoring systems have been conceived to create a standardized and reproducible way to characterize renal tumor anatomy. However, less is known about which of these individual measures are important with regard to clinically relevant perioperative outcomes such as ischemia time (IT), estimated blood loss (EBL), length of hospital stay (LOS), and change in estimated glomerular filtration rate (eGFR) after robotic partial nephrectomy (PN). We aimed to assess the utility of the RENAL and PADUA scores, their subscales, and C-index for predicting these outcomes. MATERIALS AND METHODS: We analyzed imaging studies from 283 patients who underwent robotic PN between 2008 and 2014 to assign nephrometry scores (NS): PADUA, RENAL and C-index. Univariate linear regression was used to assess whether the NS or any of their subscales were associated with EBL or IT. Multivariable linear regression and linear regression models were created to assess LOS and eGFR. RESULTS: The three NS were significantly associated with EBL, IT, LOS, and eGFR at 12 months after surgery. All subscales with the exception of anterior/posterior were significantly associated with EBL and IT. Collecting system, renal rim location, renal sinus, exophytic/endophytic, and nearness to collecting system were significant predictors for LOS. Only renal rim location, renal sinus invasion and polar location were significantly associated with eGFR at 12 months. CONCLUSIONS: Tumor size and depth are important characteristics for predicting robotic PN outcomes and thus could be used individually as a simplified way to report tumors features for research and patient counseling purposes.

Histologic subtype impacts cancer-specific survival in patients with sarcomatoid-variant renal cell carcinoma treated surgically.

PURPOSE: To report survival outcomes of patients treated surgically for sarcomatoid-variant renal cell carcinomas (sRCC) and to assess whether the underlying histologic subtype is an independent predictor of outcome. METHODS: One hundred and fifty-one patients underwent surgery at a referral center between 1991 and 2014 and had sRCC in final pathology. Kaplan-Meier curves for metastasis-free survival and cancer-specific survival (CSS) were calculated, and the log-rank test assessed differences between clear cell sRCC and nonclear cell sRCC. Cox regression models were generated to test the prognostic value of histologic subtype. RESULTS: Of 151 patients, 120 (79 %) had clear cell sRCC and 31 (21 %) had nonclear cell sRCC. Ninety-eight (65 %) patients had M0/Mx disease at presentation. Among those M0/Mx patients, metastasis-free survival probabilities were 49 % at 2 years [95 % confidence interval (CI) 38-60] and 39 % at 5 years (95 % CI 28-50), while CSS probabilities were 50 % at 2 years (95 % CI 41-58) and 32 % at 5 years (95 % CI 24-41). There was no significant difference in metastasis-free survival between clear cell and nonclear cell sRCC (p = 0.8). However, patients with nonclear cell sRCC had significantly lower CSS than patients with clear cell sRCC (p = 0.035). In multivariable analyses, nonclear cell sRCC conferred a higher risk of cancer-specific death compared with clear cell sRCC (HR 2.30, 95 % CI 1.38-3.82, p = 0.001). CONCLUSIONS: In a cohort of patients treated surgically, the underlying histologic subtype of sRCC had an impact on CSS. These results present valuable information for individual counseling and patient selection in clinical trials.

Active surveillance for prostate cancer.

It is worth distinguishing between the two strategies of expectant management for prostate cancer. Watchful waiting entails administering non-curative androgen deprivation therapy to patients on development of symptomatic progression, whereas active surveillance entails delivering curative treatment on signs of disease progression. The objectives of the two management strategies and the patients enrolled in either are different: (i) to review the role of active surveillance as a management strategy for patients with low-risk prostate cancer; and (ii) review the benefits and pitfalls of active surveillance. We carried out a systematic review of active surveillance for prostate cancer in the literature using the National Center for Biotechnology Information's electronic database, PubMed. We carried out a search in English using the terms: active surveillance, prostate cancer, watchful waiting and conservative management. Selected studies were required to have a comprehensive description of the demographic and disease characteristics of the patients at the time of diagnosis, inclusion criteria for surveillance, and a protocol for the patients' follow up. Review articles were included, but not multiple papers from the same datasets. Active surveillance appears to reduce overtreatment in patients with low-risk prostate cancer without compromising cancer-specific survival at 10 years. Therefore, active surveillance is an option for select patients who want to avoid the side-effects inherent to the different types of immediate treatment. However, inclusion criteria for active surveillance and the most appropriate method of monitoring patients on active surveillance have not yet been standardized.

Preoperative predictive model of recovery of urinary continence after radical prostatectomy.

OBJECTIVE: To build a predictive model of urinary continence recovery after radical prostatectomy (RP) that incorporates magnetic resonance imaging (MRI) parameters and clinical data. PATIENTS AND METHODS: We conducted a retrospective review of data from 2,849 patients who underwent pelvic staging MRI before RP from November 2001 to June 2010. We used logistic regression to evaluate the association between each MRI variable and continence at 6 or 12 months, adjusting for age, body mass index (BMI) and American Society of Anesthesiologists (ASA) score, and then used multivariable logistic regression to create our model. A nomogram was constructed using the multivariable logistic regression models. RESULTS: In all, 68% (1,742/2,559) and 82% (2,205/2,689) regained function at 6 and 12 months, respectively. In the base model, age, BMI and ASA score were significant predictors of continence at 6 or 12 months on univariate analysis (P < 0.005). Among the preoperative MRI measurements, membranous urethral length, which showed great significance, was incorporated into the base model to create the full model. For continence recovery at 6 months, the addition of membranous urethral length increased the area under the curve (AUC) to 0.664 for the validation set, an increase of 0.064 over the base model. For continence recovery at 12 months, the AUC was 0.674, an increase of 0.085 over the base model. CONCLUSION: Using our model, the likelihood of continence recovery increases with membranous urethral length and decreases with age, BMI and ASA score. This model could be used for patient counselling and for the identification of patients at high risk for urinary incontinence in whom to study changes in operative technique that improve urinary function after RP.

Interobserver variability of R.E.N.A.L., PADUA, and centrality index nephrometry score systems.

PURPOSE: To assess interobserver variability of R.E.N.A.L., preoperative aspects and dimensions used for an anatomical classification system (PADUA), and centrality index (C-Index) systems among observers with varying degrees of clinical experience and each system's subscale correlation with surgical outcome metrics. METHODS: Computed tomography images of 90 patients who underwent open, laparoscopic, or robot-assisted laparoscopic partial nephrectomy were scored by one radiology fellow, two urology fellows, one radiology resident, and one secondary school student. Agreement among readers was determined calculating intraclass correlation coefficients. Associations between radiology fellow scores (reference standard as reader with greatest clinical experience), ischemia time, and percent change in postoperative estimated glomerular filtration rate (eGFR) were evaluated using Spearman's correlation. RESULTS: Agreement using C-Index method (ICC = 0.773) was higher than with PADUA (ICC = 0.677) or R.E.N.A.L (ICC = 0.660). Agreement between reference and secondary school student was lower than with other physicians, although the differences were not statistically significant. The reference's scores were significantly (p < 0.05) associated with ischemia time on all three scoring systems and with percent change in eGFR at 6 weeks using C-Index (p = 0.016). Tumor size, nearness to sinus, and location relative to polar lines (R.E.N.A.L.) and tumor size, renal sinus involvement, and collecting system involvement (PADUA) correlated with ischemia time (all p ≤ 0.001). No R.E.N.A.L. or PADUA subscales significantly correlated with percent change in postoperative eGFR. CONCLUSIONS: Clinical experience reduces interobserver variability of existing nephrometry systems though not significantly and less so when using directly measureable anatomic variables. Consistently, only measures of tumor size and distance to intrarenal structures were useful in predicting clinically relevant outcomes.

Effect of repeated prostate biopsies on erectile function in men on active surveillance for prostate cancer.

PURPOSE: Active surveillance is becoming an increasingly common management strategy for low grade prostate cancer and involves repeat prostate biopsies over time. It has been hypothesized that serial biopsies can lead to reduced erectile function in patients on active surveillance and we explored this hypothesis in a longitudinally followed cohort. MATERIALS AND METHODS: We identified 342 men on active surveillance whose first biopsy occurred between 2000 and 2009. We investigated erectile function using patient reported outcomes, namely the 6 erectile function questions from the IIEF-6 (International Index of Erectile Function). We estimated the change in erectile function with time using locally weighted scatterplot smoothing. RESULTS: The median (IQR) patient age in this cohort was 64 years (58-68). Median followup on active surveillance was 3.5 years (2.3-5.0) and the median number of biopsies was 5 (3-6). During the first 4 years on active surveillance erectile function decreased 1.0 point per year (95% CI 0.2, 1.7) on the IIEF-6 (scale 1 to 30). When stratified by comorbidities or number of biopsies we see an almost identical decrease in erectile function with time. The use of phosphodiesterase-5 inhibitors increased from 5% to 27% from baseline to year 5 on active surveillance. CONCLUSIONS: In this longitudinally followed active surveillance cohort we observed a small decrease in erectile function and an increase in the use of phosphodiesterase-5 inhibitors with time. While we cannot separate out the effect of multiple biopsies from that of the natural aging process on erectile function in this observational study, our data suggest that active surveillance related biopsies do not have a large impact on erectile function.

Black and White men younger than 50 years of age demonstrate similar outcomes after radical prostatectomy.

BACKGROUND: Black men with prostate cancer are diagnosed at a younger age, present with more aggressive disease, and experience higher mortality. We sought to assess pathological features and biochemical recurrence (BCR) in young men undergoing radical prostatectomy (RP) to determine if there is a difference between black and white men closer to the time of disease initiation. METHODS: We identified 551 white and 99 black men at a tertiary cancer center who underwent RP at ≤50 years of age. Baseline and pathological features were compared between the two groups. Cox proportional hazards models were utilized to examine the association of race and BCR, and Kaplan-Meier curves were generated to determine biochemical recurrence-free survival (bRFS). RESULTS: There were no differences in median age at surgery, biopsy Gleason score, or comorbidity. Black men had higher preoperative PSA (6.1 ng/ml vs 4.7 ng/ml, p = 0.004), but a greater percentage were cT1c (78% vs 63%), compared to white men. On multivariate analysis, black men demonstrated significantly lower odds of non-organ confined disease (OR 0.39; 95% CI: 0.18, 0.81; p = 0.01) and extracapsular extension (ECE) (OR 0.38; 95% CI: 0.18, 0.81, p = 0.01), and had no difference in Gleason score upgrading and seminal vesicle invasion compared to white men. There was no significant difference in bRFS in men with organ-confined disease; however, among men with locally advanced disease black men trended towards greater BCR (p = 0.052). Black men had 2-year bRFS of 56% vs 75% in white men. CONCLUSIONS: In this single institution study, there does not appear to be a racial disparity in outcomes among younger men who receive RP for prostate cancer. Black and white men in our cohort demonstrate similar bRFS with pathologically confirmed organ-confined disease. There may be greater risk of BCR among black men locally advanced disease compared to white men, suggesting that locally advanced disease is biologically more aggressive in black men.