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Background: This study aimed to examine clinicopathologic characteristics, treatment patterns, and survival rates in a contemporary population-based cohort of adult prostate sarcoma patients., Methods: In the Surveillance, Epidemiology, and End Results database (2004-2020), adult patients with prostate sarcoma were identified. Descriptive statistics, Kaplan-Meier analyses, smoothed cumulative incidence plots, and Cox regression models were used., Results: Of 125 patients, 45 (36%) harbored leiomyosarcoma, 17 (14%) had rhabdomyosarcoma, 15 (12%) had stromal sarcoma, 17 (14%) had sarcoma not otherwise specified (NOS), and 31 (25%) had other sarcoma subtypes. Metastatic stage was most common in the rhabdomyosarcoma patients (44%) and least common in the leiomyosarcoma (21%) and stromal sarcoma (20%) patients. Most of the rhabdomyosarcoma patients received the combination of systemic and radiation therapy with (24%) or without radical surgery (35%), whereas most of the leiomyosarcoma and stromal sarcoma patients underwent radical surgery with (22 and 13%) or without (22 and 47%) radiation. In the overall population, the median overall survival was 27 months. The 5-years overall versus cancer-specific versus other-cause mortality rates were respectively 71 versus 58 versus 13%. In the multivariable Cox regression models, the highest overall mortality was exhibited by the patients with metastatic disease (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.55-5.31; p < 0.001) or unknown disease stage (HR 2.94; 95% CI 2.20-7.21; p = 0.019). Conversely, of all the histologic subtypes, only stromal sarcoma distinguished itself by lower overall mortality (HR 0.41; 95% CI 0.18-0.96; p = 0.039)., Conclusions: Four major histologic subtypes were identified. Among most adult sarcoma patients, treatment patterns vary according to histology, from multimodal therapy to radical prostatectomy alone. These treatment differences reflect equally important heterogeneity in survival patterns., (© 2024. The Author(s).)

Background: To test for differences in organ-confined pathological tumor stage (pT) and intermediate International Society of Urological Pathologists (ISUP) grade vs. nonorgan confined pT stage and high ISUP grade and biochemical recurrence (BCR) after radical prostatectomy (RP)., Methods: Relying on a tertiary-care database, prostate cancer patients undergoing RP between January 2014 and December 2021 were stratified according to their combination of pT stage and ISUP grade in RP specimens (pT2 ISUP4/5 vs. pT3/4 ISUP2 vs. pT3/4 ISUP3). As Active Surveillance is recommended in ISUP1, these patients were excluded. Moreover, patients with pT2 ISUP2/3 are known for their good prognosis and pT3/4 ISUP4/5 patients for their poor prognosis. Therefore, these patients were also excluded from analyses. Kaplan-Meier survival analyses and multivariable Cox regression models addressed BCR after RP., Results: Of 215 RP patients, 29 (13%) exhibited pT2 ISUP4/5 vs. 122 (57%) pT3/4 ISUP2 vs. 64 (30%) pT3/4 ISUP3 pathology. In survival analyses, 3-year BCR-free survival rates were 95% in pT2 ISUP4/5 vs. 88% in pT3/4 ISUP2 vs. 65% in pT3/4 ISUP3 patients (P < 0.001). In multivariable Cox regression models addressing BCR, pT3/4 ISUP3 pathology was associated with higher BCR rate relative to pT2 ISUP4/5 pathology (hazard ratio 3.42, 95% confidence interval 1.07-10.94; P = 0.039), but not pT3/4 ISUP2 pathology (P = 0.6)., Conclusion: Compared to prostate cancer patients with pT2 ISUP4/5 pathology, the combination of pT3/4 ISUP3 pathology is associated with higher risk of BCR after RP. In consequence, patients with pT3/4 ISUP3 pathology should be considered for a closer postoperative follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Metachronous metastatic prostate cancer (mmPCa) patients harbor different characteristics and outcomes, relative to DeNovo metastatic PCa patients. Onset of metastatic disease might be influenced by primary PCa characteristics such as Gleason score (GS) or cancer stage, as well as overall survival (OS) by timing of metastatic onset., Patients and Methods: We relied on an institutional tertiary-care database to identify mmPCa patients. Kaplan Meier and Cox Regression models tested for onset of metastases and OS, stratified according to GS, pathological stage and time to mmPCa., Results: Of 341 mmPCa patients, 8% harbored GS6 versus 41% versus 51% GS7 and GS8-10. Median time to onset of metastatic disease was 79 versus 54 versus 41 months for GS6 versus GS7 versus GS8-10 (P = .01). Moreover, median time to onset of metastases was 64 versus 44 months for pT1-2 versus pT3-4 mmPCa patients undergoing radical prostatectomy (P = .027). In multivariable Cox regression models, higher GS and pT-stage was associated with earlier onset of metastases. Additionally, significant OS differences could be observed for time interval of < 24 versus 24-60 versus 60-120 versus ≥ 120 months between primary PCa diagnosis and onset of mmPCa. Specifically, median OS was 56 versus 69 versus 97 months versus not reached (P < .01) for these categories. In multivariable Cox regression, shorter time to metastatic onset was associated with shorter OS., Conclusion: Timing of mmPCa is strongly influenced by grading and pT-stage in real-life setting. OS benefits can be observed with longer time interval between primary PCa diagnosis and onset of mmPCa., Competing Interests: Disclosure None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background : Biochemical recurrence (BCR) represents the rise of prostate-specific antigen (PSA) levels after treatment with curative radical prostatectomy (RP) or radiation for prostate cancer. The objective of the current study was to test for the association between patient characteristics, namely age, body mass index (BMI), as well as prostate volume at surgery, and BCR after RP. Material and Methods : Within a tertiary care database, patients with prostate cancer treated with RP between January 2014 and June 2023 were included. Kaplan-Meier survival analyses and Cox regression models addressed BCR after RP according to patient characteristics. Results : Of 821 patients, the median age was 66 years (interquartile range [IQR] 61-71 years), BMI was 26.2 kg/m 2 (IQR 24.3-28.8 kg/m 2 ), and prostate volume was 40 cm 3 (IQR 30-55 cm 3 ). Median follow-up was 20 months. In survival analyses, the three-year BCR-free survival rates were 81 vs. 84 vs. 81% in patients aged ≤60 vs. 61-69 vs. 70 years ( p = 0.1). In patients with BMI < 25.0 vs. 25.0-29.9 vs. ≥30.0 kg/m 2 , the three-year BCR-free survival rates were 84 vs. 81 vs. 84% ( p = 0.7). In patients with prostate volume ≤40 vs. >40 cm 3 , the three-year BCR-free survival rates were 85 vs. 80% ( p = 0.004). In multivariable Cox regression models accounting for patient and pathologic tumor characteristics and adjuvant radiation therapy, a higher prostate volume independently predicted BCR as continuous (hazard ratio 1.012, 95% confidence interval 1.005-1.019; p < 0.001), as well as categorized the variable based on the median (hazard ratio 1.66, 95% confidence interval 1.17-2.36; p = 0.005). Conversely, neither age nor BMI were significantly associated with BCR after RP. Conclusions : The higher prostate volume independently predicted BCR after RP, but not age or BMI at surgery. Consequently, patients with an elevated prostate volume should be considered for closer postoperative follow-up.

Objectives: Within the tertiary-case database, the authors tested for differences in long-term continence rates (≥ 12 months) between prostate cancer patients with extraprostatic vs. organ-confined disease who underwent Robotic-Assisted Radical Prostatectomy (RARP)., Method: In the institutional tertiary-care database the authors identified prostate cancer patients who underwent RARP between 01/2014 and 01/2021. The cohort was divided into two groups based on tumor extension in the final RARP specimen: patients with extraprostatic (pT3/4) vs. organ-confined (pT2) disease. Additionally, the authors conducted subgroup analyses within both the extraprostatic and organ-confined disease groups to compare continence rates before and after the implementation of the new surgical technique, which included Full Functional-Length Urethra preservation (FFLU) and Neurovascular Structure-Adjacent Frozen-Section Examination (NeuroSAFE). Multivariable logistic regression models addressing long-term continence were used., Results: Overall, the authors identified 201 study patients of whom 75 (37 %) exhibited extraprostatic and 126 (63 %) organ-confined disease. There was no significant difference in long-term continence rates between patients with extraprostatic and organ-confined disease (77 vs. 83 %; p = 0.3). Following the implementation of FFLU+ NeuroSAFE, there was an overall improvement in continence from 67 % to 89 % (Δ = 22 %; p < 0.001). No difference in the magnitude of improved continence rates between extraprostatic vs. organ-confined disease was observed (Δ = 22 % vs. Δ = 20 %). In multivariable logistic regression models, no difference between extraprostatic vs. organ-confined disease in long-term continence was observed (Odds Ratio: 0.91; p = 0.85)., Conclusion: In this tertiary-based institutional study, patients with extraprostatic and organ-confined prostate cancer exhibited comparable long-term continence rates., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Aim and Objectives : We aimed to test the impact of age on long-term urinary continence (≥12 months) in patients undergoing robotic-assisted radical prostatectomy. Methods and Materials : We relied on an institutional tertiary-care database to identify the patients who underwent robotic-assisted radical prostatectomy between January 2014 and January 2021. Patients were divided into three age groups: age group one (≤60 years), age group two (61-69 years) and age group three (≥70 years). Multivariable logistic regression models tested the differences between the age groups in the analyses addressing long-term urinary continence after robotic-assisted radical prostatectomy. Results : Of the 201 prostate cancer patients treated with robotic-assisted radical prostatectomy, 49 (24%) were assigned to age group one (≤60 years), 93 (46%) to age group two (61-69 years) and 59 (29%) to age group three (≥70 years). The three age groups differed according to long-term urinary continence: 90% vs. 84% vs. 69% for, respectively, age group one vs. two vs. three ( p = 0.018). In the multivariable logistic regression, age group one (Odds Ratio (OR) 4.73, 95% CI 1.44-18.65, p = 0.015) and 2 (OR 2.94; 95% CI 1.23-7.29; p = 0.017) were independent predictors for urinary continence, compared to age group three. Conclusion : Younger age, especially ≤60 years, was associated with better urinary continence after robotic-assisted radical prostatectomy. This observation is important at the point of patient education and should be discussed in informed consent.

The objective of the study was to test the impact of implementing standard full functional-length urethral sphincter (FFLU) and neurovascular bundle preservation (NVBP) with intraoperative frozen section technique (IFT) on long-term urinary continence in patients undergoing robotic-assisted radical prostatectomy (RARP). We relied on an institutional tertiary-care database to identify patients who underwent RARP between 01/2014 and 09/2019. Until 10/2017, FFLU was not performed and decision for NVBP was taken without IFT. From 11/2017, FFLU and IFT-guided NVBP was routinely performed in all patients undergoing RARP. Long-term continence (≥ 12 months) was defined as the usage of no or one safety- pad. Uni- and multivariable logistic regression models tested the correlation between surgical approach (standard vs FFLU + NVBP) and long-term continence. Covariates consisted of age, body mass index, prostate volume and extraprostatic extension of tumor. The study cohort consisted of 142 patients, with equally sized groups for standard vs FFLU + NVBP RARP (68 vs 74 patients). Routine FFLU + NVBP implementation resulted in a long-term continence rate of 91%, compared to 63% in standard RARP (p < 0.001). Following FFLU + NVBP RARP, 5% needed 1-2, 4% 3-5 pads/24 h and no patient (0%) suffered severe long-term incontinence (> 5 pads/24 h). No significant differences in patient or tumor characteristics were recorded between both groups. In multivariable logistic regression models, FFLU + NVBP was a robust predictor for continence (Odds ratio [OR]: 7.62; 95% CI 2.51-27.36; p < 0.001). Implementation of FFLU and NVBP in patients undergoing RARP results in improved long-term continence rates of 91%., (© 2022. The Author(s).)

The aim of this study is to investigate the incidental prostate cancer (iPCa) detection rates of different embedding methods in a large, contemporary cohort of patients with bladder outlet obstruction (BOO) treated with transurethral surgery. We relied on an institutional tertiary-care database to identify BOO patients who underwent either transurethral loop resection or laser (Holmium:yttrium-aluminium garnet) enucleation of the prostate (HoLEP) between 01/2012 and 12/2019. Embedding methods differed with regard to the extent of the additional prostate tissue submitted following the first ten cassettes of primary embedding (cohort A: one [additional] cassette/10 g residual tissue vs. cohort B: complete embedding of the residual tissue). Detection rates of iPCa among the different embedding methods were compared. Subsequently, subgroup analyses by embedding protocol were repeated in HoLEP-treated patients only. In the overall cohort, the iPCa detection rate was 11% (46/420). In cohort A (n = 299), tissue embedding resulted in a median of 8 cassettes/patient (range 1-38) vs. a median of 15 (range 2-74) in cohort B (n = 121) (p < .001). The iPCa detection rate was 8% (23/299) and 19% (23/121) in cohort A vs. cohort B, respectively (p < .001). Virtual reduction of the number of tissue cassettes to ten cassettes resulted in a iPCa detection rate of 96% in both cohorts, missing one stage T1a/ISUP grade 1 carcinoma. Increasing the number of cassettes by two and eight cassettes, respectively, resulted in a detection rate of 100% in both cohorts without revealing high-grade carcinomas. Subgroup analyses in HoLEP patients confirmed these findings, demonstrated by a 100 vs. 96% iPCa detection rate following examination of the first ten cassettes, missing one case of T1a/ISUP 1. Examination of 8 additional cassettes resulted in a 100% detection rate. The extent of embedding of material obtained from transurethral prostate resection correlates with the iPCa detection rate. However, the submission of 10 cassettes appears to be a reasonable threshold to reduce resource utilization while maintaining secure cancer detection., (© 2022. The Author(s).)

Objective: Not infrequently patients are diagnosed with clinically localized prostate based on a single positive biopsy core exhibiting Gleason grade group 1 (GGG1) with variable prostate-specific antigen (PSA) levels. We investigated treatment patterns and hypothesized that regardless of PSA in cT1- to cT2-stage patients, presence of GGG3/GGG4/GGG5 and/or non-organ confined stage will rarely be identified., Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2015), clinically localized prostate cancer (CaP) patients with PSA ≤ 50 ng/ml and a single positive GGG1 biopsy core were identified. Overall treatment rates were examined, estimated annual percentage changes and logistic regression analyses were fitted to test for no-local treatment. Subsequently, rates of upgrading (GGG3/GGG4/GGG5) and/or upstaging (≥pT3 and/or pN1) were investigated in radical prostatectomy patients., Results: 13,342 clinically localized CaP patients harbored single GGG1 positive biopsy core at diagnosis. No local treatment was recorded in 5,235 (53.0%) cT1-stage vs. in 1,039 (49.0%) cT2-stage patients. No local treatment rates increased over time from 35.0% to 67.0% vs. 34.0% to 63.0% in cT1 vs. cT2 patients, observations were confirmed in logistic regression analyses (cT1: multivariable odds ratio [mOR]: 1.39; cT2: mOR: 1.33). In radical prostatectomy treated cT1-patients (n = 2,293) and cT2-patients (n = 659), upgrading vs. upstaging vs. upgrading/upstaging combined was 6.1%, 6.5%, 11.0% and 6.2%, 5.0%, 9.9% respectively., Conclusions: In single GGG1 positive biopsy core CaP patients, the combined proportion of upgrading and upstaging should be expected in one tenth. In consequence, the overwhelming majority harbors favorable grade and stage that is compatible with no local treatment., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Some high-risk prostate cancer (PCa) patients may show more favorable Gleason pattern at radical prostatectomy (RP) than at biopsy., Objective: To test whether downgrading could be predicted accurately., Design, Setting, and Participants: Within the Surveillance, Epidemiology and End Results database (2010-2016), 6690 National Comprehensive Cancer Network (NCCN) high-risk PCa patients were identified., Outcome Measurements and Statistical Analyses: We randomly split the overall cohort between development and validation cohorts (both n = 3345, 50%). Multivariable logistic regression models used biopsy Gleason, prostate-specific antigen, number of positive prostate biopsy cores, and cT stage to predict downgrading. Accuracy, calibration, and decision curve analysis (DCA) tested the model in the external validation cohort., Results and Limitations: Of 6690 patients, 50.3% were downgraded at RP, and of 2315 patients with any biopsy pattern 5, 44.1% were downgraded to RP Gleason pattern ≤4 + 4. Downgrading rates were highest in biopsy Gleason pattern 5 + 5 (84.1%) and lowest in 3 + 4 (4.0%). In the validation cohort, the logistic regression model-derived nomogram predicted downgrading with 71.0% accuracy, with marginal departures (±3.3%) from ideal predictions in calibration. In DCA, a net benefit throughout all threshold probabilities was recorded, relative to treat-all or treat-none strategies and an algorithm based on an average downgrading rate of 50.3%. All steps were repeated in the subgroup with any biopsy Gleason pattern 5, to predict RP Gleason pattern ≤4 + 4. Here, a second nomogram (n = 2315) yielded 68.0% accuracy, maximal departures from ideal prediction of ±5.7%, and virtually the same DCA pattern as the main nomogram., Conclusions: Downgrading affects half of all high-risk PCa patients. Its presence may be predicted accurately and may help with better treatment planning., Patient Summary: Downgrading occurs in every second high-risk prostate cancer patients. The nomograms developed by us can predict these probabilities accurately., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: No North-American study tested the survival benefit of chemotherapy in de novo metastatic prostate cancer according to race/ethnicity. We addressed this void., Methods: We identified de novo metastatic prostate cancer patients within the Surveillance, Epidemiology, and End Results database (2014-2015). Separate and specific Kaplan-Meier plots and Cox regression models tested for overall survival differences between chemotherapy-exposed versus chemotherapy-naïve patients in four race/ethnicity groups: Caucasian versus African-American versus Hispanic/Latino vs Asian. Race/ethnicity specific propensity score matching was applied. Here, additional landmark analysis was performed., Results: Of 4232 de novo metastatic prostate cancer patients, 2690 (63.3%) were Caucasian versus 783 (18.5%) African-American versus 504 (11.8%) Hispanic/Latino versus 257 (6.1%) Asian. Chemotherapy rates were: 21.3% versus 20.8% versus 21.0% versus 20.2% for Caucasians versus African-Americans versus Hispanic/Latinos versus Asians, respectively. At 30 months of follow-up, overall survival rates between chemotherapy-exposed versus chemotherapy-naïve patients were 61.5 versus 53.2% (multivariable hazard ratio [mHR]: 0.76, 95 confidence interval [CI]: 0.63-0.92, p = 0.004) in Caucasians, 55.2 versus 51.6% (mHR: 0.76, 95 CI: 0.54-1.07, p = 0.11) in African-Americans, 62.8 versus 57.0% (mHR: 1.11, 95 CI: 0.73-1.71, p = 0.61) in Hispanic/Latinos and 77.7 versus 65.0% (mHR: 0.31, 95 CI: 0.11-0.89, p = 0.03) in Asians. Virtually the same findings were recorded after propensity score matching within each race/ethnicity group., Conclusions: Caucasian and Asian de novo metastatic prostate cancer patients exhibit the greatest overall survival benefit from chemotherapy exposure. Conversely, no overall survival benefit from chemotherapy exposure could be identified in either African-Americans or Hispanic/Latinos. Further studies are clearly needed to address these race/ethnicity specific disparities., (© 2022 The Authors. The Prostate published by Wiley Periodicals LLC.)

Background: The pathological stage of prostate cancer with high-risk prostate-specific antigen (PSA) levels, but otherwise favorable and/or intermediate risk characteristics (clinical T-stage, Gleason Grade group at biopsy [B-GGG]) is unknown. We hypothesized that a considerable proportion of such patients will exhibit clinically meaningful GGG upgrading or non-organ confined (NOC) stage at radical prostatectomy (RP)., Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2015) we identified RP-patients with cT1c-stage and B-GGG1, B-GGG2, or B-GGG3 and PSA 20-50 ng/ml. Rates of GGG4 or GGG5 and/or rates of NOC stage (≥ pT3 and/or pN1) were analyzed. Subsequently, separate univariable and multivariable logistic regression models tested for predictors of NOC stage and upgrading at RP., Results: Of 486 assessable patients, 134 (28%) exhibited B-GGG1, 209 (43%) B-GGG2, and 143 (29%) B-GGG3, respectively. The overall upgrading and NOC rates were 11% and 51% for a combined rate of upgrading and/or NOC stage of 53%. In multivariable logistic regression models predicting upgrading, only B-GGG3 was an independent predictor (odds ratio [OR]: 5.29; 95% confidence interval [CI]: 2.21-14.19; p < 0.001). Conversely, 33%-66% (OR: 2.36; 95% CI: 1.42-3.95; p = 0.001) and >66% of positive biopsy cores (OR: 4.85; 95% CI: 2.84-8.42; p < 0.001), as well as B-GGG2 and B-GGG3 were independent predictors for NOC stage (all p ≤ 0.001)., Conclusions: In cT1c-stage patients with high-risk PSA baseline, but low- to intermediate risk B-GGG, the rate of upgrading to GGG4 or GGG5 is low (11%). However, NOC stage is found in the majority (51%) and can be independently predicted with percentage of positive cores at biopsy and B-GGG., (© 2022 The Authors. The Prostate published by Wiley Periodicals LLC.)

Background: We aimed to determine the concordance between the radiologic stage (rT), using multiparametric magnetic resonance imaging (mpMRI), and pathologic stage (pT) in patients with high-risk prostate cancer and its influence on nerve-sparing surgery compared to the use of the intraoperative frozen section technique (IFST)., Methods: The concordance between rT and pT and the rates of nerve-sparing surgery and positive surgical margin were assessed for patients with high-risk prostate cancer who underwent radical prostatectomy., Results: The concordance between the rT and pT stages was shown in 66.4% ( n = 77) of patients with clinical high-risk prostate cancer. The detection of patients with extraprostatic disease (≥pT3) by preoperative mpMRI showed a sensitivity, negative predictive value and accuracy of 65.1%, 51.7% and 67.5%. In addition to the suspicion of extraprostatic disease in mpMRI (≥rT3), 84.5% ( n = 56) of patients with ≥rT3 underwent primary nerve-sparing surgery with IFST, resulting in 94.7% ( n = 54) of men with at least unilateral nerve-sparing surgery after secondary resection with a positive surgical margin rate related to an IFST of 1.8% ( n = 1)., Conclusion: Patients with rT3 should not be immediately excluded from nerve-sparing surgery, as by using IFST some of these patients can safely undergo nerve-sparing surgery.

Context: Novel prospective randomized controlled observations addressing combination therapy in metastatic hormone-sensitive prostate cancer (mHSPC) have demonstrated promising overall survival (OS) outcomes., Objective: To compare these novel findings and systematically review and address them within formal network meta-analyses (NMAs) that include observations from other prospective randomized controlled trials (RCTs)., Evidence Acquisition: First, we focused on abiraterone, enzalutamide, apalutamide, and docetaxel effects on OS in mHSPC using the PRISMA methodology. PubMed and abstracts identified prospective RCTs in first-line mHSPC. Second, we focused on mature studies that reached median OS and tested OS between abiraterone and docetaxel with tumor burden stratification., Evidence Synthesis: The first part included seven studies (n = 6639) and the second part, five studies (n = 4462). In the first part, abiraterone ranked first for high-volume mHSPC. Conversely, enzalutamide ranked first for low-volume mHSPC. In the second part, abiraterone treatment in high-volume mHSPC resulted in median OS of 50.1 mo and exceeded that with docetaxel (45.9 mo) and ADT alone (34.0 mo). Docetaxel treatment in low volume mHSPC resulted in median OS of 69.5 mo versus 67.7 mo with ADT alone., Conclusions: In conventional NMA that relied on conventional hazard ratios, differences were identified with respect to the relative efficacy of the combination therapies examined; abiraterone dominated the alternatives in high-volume mHSPC. In part two, which relied on trials for which median OS is available, comparison of abiraterone versus docetaxel revealed a 4-mo difference in OS in high-volume mHSPC. Conventional NMA may have overestimated the importance of treatment efficacy instead of focusing on median OS duration, which might represent a more important clinical endpoint., Patient Summary: We reviewed studies on hormonal treatments and chemotherapy used for prostate cancer that has spread outside the prostate gland (metastatic prostate cancer, mPC). We found that the best overall survival was with the hormone agents abiraterone in high-volume mPC and enzalutamide in low-volume mPC. In comparison to the chemotherapy drug docetaxel, median overall survival with abiraterone was 4 months longer among patients with mPC., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To determine the feasibility and outcome of radical prostatectomy (RP) following neoadjuvant therapy (NAT) in patients with initial inoperable, rectum-infiltrating cT4 prostate cancer (PCa)., Methods: From 01/2018 to 12/2020, 26 patients with clinical (DRE) or radiographical (mpMRI) suspicion of rectum infiltrating PCa at diagnosis and NAT prior to RP were retrospectively identified from our prospective institutional database. Two patients were still inoperable after NAT. Downsizing was administered for at least 20 weeks and RP was performed after excluding ongoing rectal infiltration., Results: At diagnosis, median PSA was 42.5 ng/ml (IQR: 23.0-66.1). Inductive NAT consisted of androgen deprivation therapy (ADT) in combination with chemotherapy (n = 9) or without chemotherapy (n = 14). Median preoperative PSA was 0.93 ng/ml (IQR: 0.24-0.40). Median time from NAT to RP was 6 months (IQR: 5-7). Two patients were still inoperable after NAT. Of 24 patients undergoing RP, abortion of surgery due to inoperability was observed in 2 patients (8.4%), demonstrating a total failure rate of NAT in 4 out of 26 patients (15.4%). One patient suffered a rectal injury with consecutive colostomy (4.2%). No Clavien-Dindo complication Grade IV or V were observed. Urinary continence was achieved in 16 patients (84.2%). Sufficient erection for sexual intercourse was present in 2 patients (10.5%). All patients received adjuvant ADT with or without radiation therapy. Median PSA at 13 months was 0.08 ng/ml (IQR: 0.01-0.74)., Conclusion: RP of initially rectum infiltrating PCa is feasible and safe after inductive NAT, however complications rates tend to be higher compared to standard RP., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To test for differences in cancer-specific mortality (CSM) rates in Hispanic/Latino prostate cancer patients according to treatment type, radical prostatectomy (RP) vs external beam radiotherapy (EBRT)., Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 2290 NCCN (National Comprehensive Cancer Network) high-risk (HR) Hispanic/Latino prostate cancer patients. Of those, 893 (39.0%) were treated with RP vs 1397 (61.0%) with EBRT. First, cumulative incidence plots and competing risks regression models tested for CSM differences after adjustment for other cause mortality (OCM). Second, cumulative incidence plots and competing risks regression models were refitted after 1:1 propensity score matching (according to age, PSA, biopsy Gleason score, cT-stage, cN-stage)., Results: In NCCN HR patients, 5-year CSM rates for RP vs EBRT were 2.4 vs 4.7%, yielding a multivariable hazard ratio of 0.37 (95% CI 0.19-0.73, p = 0.004) favoring RP. However, after propensity score matching, the hazard ratio of 0.54 was no longer statistically significant (95% CI 0.21-1.39, p = 0.2)., Conclusion: Without the use of strictest adjustment for population differences, NCCN high-risk Hispanic/Latino prostate cancer patients appear to benefit more of RP than EBRT. However, after strictest adjustment for baseline patient and tumor characteristics between RP and EBRT cohorts, the apparent CSM benefit of RP is no longer statistically significant. In consequence, in Hispanic/Latino NCCN high-risk patients, either treatment modality results in similar CSM outcome., (© 2021. The Author(s).)

Background: To test for differences in cancer-specific mortality (CSM) rates between radical prostatectomy (RP) vs external beam radiotherapy (EBRT) in National Comprehensive Cancer Network (NCCN) high-risk African American patients, as well as Johns Hopkins University (JHU) high-risk and very high-risk patients., Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 4165 NCCN high-risk patients, of whom 1944 (46.7%) and 2221 (53.3%) patients qualified for JHU high-risk or very high-risk definitions. Of all 4165 patients, 1390 (33.5%) were treated with RP versus 2775 (66.6%) with EBRT. Cumulative incidence plots and competing risks regression models addressed CSM before and after 1:1 propensity score matching between RP and EBRT NCCN high-risk patients. Subsequently, analyses were repeated separately in JHU high-risk and very high-risk subgroups. Finally, all analyses were repeated after landmark analyses were applied., Results: In the NCCN high-risk cohort, 5-year CSM rates for RP versus EBRT were 2.4 versus 5.2%, yielding a multivariable hazard ratio of 0.50 (95% confidence interval [CI] 0.30-0.84, p = 0.009) favoring RP. In JHU very high-risk patients 5-year CSM rates for RP versus EBRT were 3.7 versus 8.4%, respectively, yielding a multivariable hazard ratio of 0.51 (95% CI: 0.28-0.95, p = 0.03) favoring RP. Conversely, in JHU high-risk patients, no significant CSM difference was recorded between RP vs EBRT (5-year CSM rates: 1.3 vs 1.3%; multivariable hazard ratio: 0.55, 95% CI: 0.16-1.90, p = 0.3). Observations were confirmed in propensity score-matched and landmark analyses adjusted cohorts., Conclusions: In JHU very high-risk African American patients, RP may hold a CSM advantage over EBRT, but not in JHU high-risk African American patients., (© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.)

Introduction: Over the last decade, multiple clinical trials demonstrated improved survival after chemotherapy for metastatic prostate cancer (mPCa). However, real-world data validating this effect within large-scale epidemiological data sets are scarce. We addressed this void., Materials and Methods: Men with de novo mPCa were identified and systemic chemotherapy status was ascertained within the Surveillance, Epidemiology, and End Results database (2004-2016). Patients were divided between historical (2004-2013) versus contemporary (2014-2016). Chemotherapy rates were plotted over time. Kaplan-Meier plots and Cox regression models with additional multivariable adjustments addressed overall and cancer-specific mortality. All tests were repeated in propensity-matched analyses., Results: Overall, 19,913 patients had de novo mPCa between 2004 and 2016. Of those, 1838 patients received chemotherapy. Of 1838 chemotherapy-exposed patients, 903 were historical, whereas 905 were contemporary. Chemotherapy rates increased from 5% to 25% over time. Median overall survival was not reached in contemporary patients versus was 24 months in historical patients (hazard ratio [HR]: 0.55, p < 0.001). After propensity score matching and additional multivariable adjustment (age, prostate-specific antigen, GGG, cT-stage, cN-stage, cM-stage, and local treatment) a HR of 0.55 (p < 0.001) was recorded. Analyses were repeated for cancer-specific mortality after adjustment for other cause mortality in competing risks regression models and recorded virtually the same findings before and after propensity score matching (HR: 0.55, p < 0.001)., Conclusions: In mPCa patients, chemotherapy rates increased over time. A concomitant increase in survival was also recorded., (© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.)

Background: To analyze postoperative, in-hospital, complication rates in patients with organ transplantation before radical prostatectomy (RP)., Methods: From National Inpatient Sample (NIS) database (2000-2015) prostate cancer patients treated with RP were abstracted and stratified according to prior organ transplant versus nontransplant. Multivariable logistic regression models predicted in-hospital complications., Results: Of all eligible 202,419 RP patients, 216 (0.1%) underwent RP after prior organ transplantation. Transplant RP patients exhibited higher proportions of Charlson comorbidity index ≥2 (13.0% vs. 3.0%), obesity (9.3% vs. 5.6%, both p < 0.05), versus to nontransplant RP. Of transplant RP patients, 96 underwent kidney (44.4%), 44 heart (20.4%), 40 liver (18.5%), 30 (13.9%) bone marrow, <11 lung (<5%), and <11 pancreatic (<5%) transplantation before RP. Within transplant RP patients, rates of lymph node dissection ranged from 37.5% (kidney transplant) to 60.0% (bone marrow transplant, p < 0.01) versus 51% in nontransplant patients. Regarding in-hospital complications, transplant patients more frequently exhibited, diabetic (31.5% vs. 11.6%, p < 0.001), major (7.9% vs. 2.9%) cardiac complications (3.2% vs. 1.2%, p = 0.01), and acute kidney failure (5.1% vs. 0.9%, p < 0.001), versus nontransplant RP. In multivariable logistic regression models, transplant RP patients were at higher risk of acute kidney failure (odds ratio [OR]: 4.83), diabetic (OR: 2.81), major (OR: 2.39), intraoperative (OR: 2.38), cardiac (OR: 2.16), transfusion (OR: 1.37), and overall complications (1.36, all p < 0.001). No in-hospital mortalities were recorded in transplant patients after RP., Conclusions: Of all transplants before RP, kidney ranks first. RP patients with prior transplantation have an increased risk of in-hospital complications. The highest risk, relative to nontransplant RP patients appears to acute kidney failure., (© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.)

Background: To determine the correlation between urine loss in PAD-test after catheter removal, and early urinary continence (UC) in RP treated patients., Methods: Urine loss was measured by using a standardized, validated PAD-test within 24 h after removal of the transurethral catheter, and was grouped as a loss of <1, 1-10, 11-50, and >50 g of urine, respectively. Early UC (median: 3 months) was defined as the usage of no or one safety-pad. Uni- and multivariable logistic regression models tested the correlation between PAD-test results and early UC. Covariates consisted of age, BMI, nerve-sparing approach, prostate volume, and extraprostatic extension of tumor., Results: From 01/2018 to 03/2021, 100 patients undergoing RP with data available for a PAD-test and early UC were retrospectively identified. Ultimately, 24%, 47%, 15%, and 14% of patients had a loss of urine <1 g, 1-10 g, 11-50 g, and >50 g in PAD-test, respectively. Additionally, 59% of patients reported to be continent. In multivariable logistic regression models, urine loss in PAD-test predicted early UC (OR: 0.21 vs. 0.09 vs. 0.03; for urine loss 1-10 g vs. 11-50 g vs. >50 g, Ref: <1 g; all p < 0.05)., Conclusions: Urine loss after catheter removal strongly correlated with early continence as well as a severity in urinary incontinence.

Background: Number of positive prostate biopsy cores represents a key determinant between high versus very high-risk prostate cancer (PCa). We performed a critical appraisal of the association between the number of positive prostate biopsy cores and CSM in high versus very high-risk PCa., Methods: Within Surveillance, Epidemiology, and End Results database (2010-2016), 13,836 high versus 20,359 very high-risk PCa patients were identified. Discrimination according to 11 different positive prostate biopsy core cut-offs (≥2-≥12) were tested in Kaplan-Meier, cumulative incidence, and multivariable Cox and competing risks regression models., Results: Among 11 tested positive prostate biopsy core cut-offs, more than or equal to 8 (high-risk vs. very high-risk: n = 18,986 vs. n = 15,209, median prostate-specific antigen [PSA]: 10.6 vs. 16.8 ng/ml, <.001) yielded optimal discrimination and was closely followed by the established more than or equal to 5 cut-off (high-risk vs. very high-risk: n = 13,836 vs. n = 20,359, median PSA: 16.5 vs. 11.1 ng/ml, p < .001). Stratification according to more than or equal to 8 positive prostate biopsy cores resulted in CSM rates of 4.1 versus 14.2% (delta: 10.1%, multivariable hazard ratio: 2.2, p < .001) and stratification according to more than or equal to 5 positive prostate biopsy cores with CSM rates of 3.7 versus 11.9% (delta: 8.2%, multivariable hazard ratio: 2.0, p < .001) in respectively high versus very high-risk PCa., Conclusions: The more than or equal to 8 positive prostate biopsy cores cutoff yielded optimal results. It was very closely followed by more than or equal to 5 positive prostate biopsy cores. In consequence, virtually the same endorsement may be made for either cutoff. However, more than or equal to 5 positive prostate biopsy cores cutoff, based on its existing wide implementation, might represent the optimal choice., (© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.)

Background: Recently, an increase in the rates of high-risk prostate cancer (PCa) was reported. We tested whether the rates of and low, intermediate, high and very high-risk PCa changed over time. We also tested whether the number of prostate biopsy cores contributed to changes rates over time., Methods: Within the Surveillance, Epidemiology and End Results (SEER) database (2010-2015), annual rates of low, intermediate, high-risk according to traditional National Comprehensive Cancer Network (NCCN) and high versus very high-risk PCa according to Johns Hopkins classification were tabulated without and with adjustment for the number of prostate biopsy cores., Results: In 119,574 eligible prostate cancer patients, the rates of NCCN low, intermediate, and high-risk PCa were, respectively, 29.7%, 47.8%, and 22.5%. Of high-risk patients, 39.6% and 60.4% fulfilled high and very high-risk criteria. Without adjustment for number of prostate biopsy cores, the estimated annual percentage changes (EAPC) for low, intermediate, high and very high-risk were respectively -5.5% (32.4%-24.9%, p < .01), +0.5% (47.6%-48.4%, p = .09), +4.1% (8.2%-9.9%, p < .01), and +8.9% (11.8%-16.9%, p < .01), between 2010 and 2015. After adjustment for number of prostate biopsy cores, differences in rates over time disappeared and ranged from 29.8%-29.7% for low risk, 47.9%-47.9% for intermediate risk, 8.9%-9.0% for high-risk, and 13.6%-13.6% for very high-risk PCa (all p > .05)., Conclusions: The rates of high and very high-risk PCa are strongly associated with the number of prostate biopsy cores, that in turn may be driven by broader use magnetic resonance imaging (MRI)., (© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.)

Objective: To test for baseline prostate cancer characteristics and survival differences after salvage radical prostatectomy (SRP) across 18 Surveillance, Epidemiology and End Results (SEER) registries from 2004 to 2016., Methods: We tabulated prostate-specific antigen (PSA), cT stage, age, and SRP rates across individual SEER registries. Kaplan-Meier and competing risks regression methodologies depicted cancer-specific mortality and other cause mortality. Finally, overall mortality was compared with predicted life expectancy., Results: Overall, 428 SRP patients (2004-2016) were identified in the SEER database. Median follow-up duration was 74 months (interquartile range [IQR], 31-114). The median age at diagnosis was 68 years (IQR, 61-73 years) with a median PSA at diagnosis of 8.8 ng/mL (IQR, 5.4-18.6 ng/mL) and 10% cT3-4 stage (0%-23.8%). Variability existed across individual SEER registries regarding age, PSA, cT stage, and annual number of SRPs (0-17), as well as cumulative numbers of SRPs (7-73) between 2004 and 2016. At 10 years, cancer-specific mortality was 23.2% vs. other cause mortality 19.3%. Finally, SRP patients exhibited higher 10-year overall mortality (43.3%) than predicted by life tables (31.8%)., Conclusion: SRP is rarely performed. In most SEER registries, SRP use is very occasional. More than 2 average annual SRPs were reported in only 5 of all registries. Nonetheless, across all registries, SRP patients showed marginal to moderate differences in PSA, cT stage, and age at diagnosis. However, at 10 years of follow-up, 1 of 5 SRP patients died of other causes and observed overall mortality was higher than expected (36%)., Competing Interests: Declaration of Competing Interest The authors have stated that they have no conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

Background: To test for rates of other cause mortality (OCM) and cancer-specific mortality (CSM) in elderly prostate cancer (PCa) patients treated with the combination of radical prostatectomy (RP) and external beam radiation therapy (EBRT) versus RP alone, since elderly PCa patients may be over-treated., Methods: Within the Surveillance, Epidemiology and End Results database (2004-2016), cumulative incidence plots, after propensity score matching for cT-stage, cN-stage, prostate specific antigen, age and biopsy Gleason score, and multivariable competing risks regression models (socioeconomic status, pathological Gleason score) addressed OCM and CSM in patients (70-79, 70-74, and 75-79 years) treated with RP and EBRT versus RP alone., Results: Of 18,126 eligible patients aged 70-79 years, 2520 (13.9%) underwent RP and EBRT versus 15,606 (86.1%) RP alone. After propensity score matching, 10-year OCM rates were respectively 27.9 versus 20.3% for RP and EBRT versus RP alone (p < .001), which resulted in a multivariable HR of 1.4 (p < .001). Moreover, 10-year CSM rates were respectively 13.4 versus 5.5% for RP and EBRT versus RP alone. In subgroup analyses separately addressing 70-74 year old and 75-79 years old PCa patients, 10-year OCM rates were 22.8 versus 16.2% and 39.5 versus 24.0% for respectively RP and EBRT versus RP alone patients (all p < .001)., Conclusion: Elderly patients treated with RP and EBRT exhibited worrisome rates of OCM. These higher than expected OCM rates question the need for combination therapy (RP and EBRT) in elderly PCa patients and indicate the need for better patient selection, when combination therapy is contemplated., (© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.)

Purpose: We hypothesized that differences in active treatment rates may exist according to race/ethnicity in favorable as well as unfavorable intermediate risk prostate cancer., Materials and Methods: We relied on the Surveillance, Epidemiology, and End Results 18 database 2010-2015. We stratified according to 3 racial/ethnic groups (White vs Black vs Hispanic) and prostate cancer baseline characteristics (prostate specific antigen, clinical T stage, Gleason group grading, percentage of biopsy cores). We tabulated active treatment rates (radical prostatectomy, external beam radiotherapy) without and with adjustment for baseline age and prostate cancer characteristics., Results: Baseline prostate specific antigen, clinical T stage, Gleason grade and percentage of positive biopsy cores differed according to racial/ethnic groups in both favorable and unfavorable intermediate risk prostate cancer patients (all p <0.05). Similarly, radical prostatectomy and external beam radiotherapy rates differed according to race/ethnicity in both favorable and unfavorable intermediate risk prostate cancer patients. Radical prostatectomy and external beam radiotherapy rates respectively ranged from 31.7%-41.8% and 26.3%-31.0% in favorable intermediate risk cases and from 33.4%-43.9% and 30.9%-35.5% in unfavorable intermediate risk prostate cancer, across the 3 race/ethnicity groups (both p <0.05). The above heterogeneity in active treatment rates disappeared and marginal differences remained after adjustment for baseline age and prostate cancer characteristics., Conclusions: Interpretation of active treatment rates in favorable and unfavorable intermediate risk prostate cancer may be severely biased, unless detailed and systematic consideration or adjustment for baseline age and prostate cancer characteristic is enforced.

Purpose: To test the effect of anatomic variants of the prostatic apex overlapping the membranous urethra (Lee type classification), as well as median urethral sphincter length (USL) in preoperative multiparametric magnetic resonance imaging (mpMRI) on the very early continence in open (ORP) and robotic-assisted radical prostatectomy (RARP) patients., Methods: In 128 consecutive patients (01/2018-12/2019), USL and the prostatic apex classified according to Lee types A-D in mpMRI prior to ORP or RARP were retrospectively analyzed. Uni- and multivariable logistic regression models were used to identify anatomic characteristics for very early continence rates, defined as urine loss of ≤ 1 g in the PAD-test., Results: Of 128 patients with mpMRI prior to surgery, 76 (59.4%) underwent RARP vs. 52 (40.6%) ORP. In total, median USL was 15, 15 and 10 mm in the sagittal, coronal and axial dimensions. After stratification according to very early continence in the PAD-test (≤ 1 g vs. > 1 g), continent patients had significantly more frequently Lee type D (71.4 vs. 54.4%) and C (14.3 vs. 7.6%, p = 0.03). In multivariable logistic regression models, the sagittal median USL (odds ratio [OR] 1.03) and Lee type C (OR: 7.0) and D (OR: 4.9) were independent predictors for achieving very early continence in the PAD-test., Conclusion: Patients' individual anatomical characteristics in mpMRI prior to radical prostatectomy can be used to predict very early continence. Lee type C and D suggest being the most favorable anatomical characteristics. Moreover, longer sagittal median USL in mpMRI seems to improve very early continence rates.

Background: To test the value of immunohistochemistry (IHC) staining in prostate biopsies for changes in biopsy results and its impact on treatment decision-making., Methods: Between January 2017-June 2020, all patients undergoing prostate biopsies were identified and evaluated regarding additional IHC staining for diagnostic purpose. Final pathologic results after radical prostatectomy (RP) were analyzed regarding the effect of IHC at biopsy., Results: Of 606 biopsies, 350 (58.7%) received additional IHC staining. Of those, prostate cancer (PCa) was found in 208 patients (59.4%); while in 142 patients (40.6%), PCa could be ruled out through IHC. IHC patients harbored significantly more often Gleason 6 in biopsy ( p < 0.01) and less suspicious baseline characteristics than patients without IHC. Of 185 patients with positive IHC and PCa detection, IHC led to a change in biopsy results in 81 (43.8%) patients. Of these patients with changes in biopsy results due to IHC, 42 (51.9%) underwent RP with 59.5% harboring ≥pT3 and/or Gleason 7-10., Conclusions: Patients with IHC stains had less suspicious characteristics than patients without IHC. Moreover, in patients with positive IHC and PCa detection, a change in biopsy results was observed in >40%. Patients with changes in biopsy results partly underwent RP, in which 60% harbored significant PCa.

Background: We hypothesized that lymph node dissection (LND) at salvage radical prostatectomy may be associated with lower cancer-specific mortality (CSM) and we tested this hypothesis., Methods: We relied on surveillance, epidemiology, and end results (2004-2016) to identify all salvage radical prostatectomy patients. Categorical, as well as univariate and multivariate Cox regression models tested the effect of LND (LND performed vs. not), as well as at its extent (log-transformed lymph node count) on CSM., Results: Of 427 salvage radical prostatectomy patients, 120 (28.1%) underwent LND with a median lymph node count of 6 (interquartile range [IQR], 3-11). According to LND status, no significant or clinically meaningful differences were recorded in PSA at diagnosis, stage and biopsy Gleason score at diagnosis, except for age at prostate cancer diagnosis (LND performed 63 vs. 68 years LND not performed, p < .001). LND status (performed) was an independent predictor of lower CSM (hazard ratio [HR] 0.47; p = .03). Similarly, lymph node count (log transformed) also independently predicted lower CSM (HR: 0.60; p = .01). After the 7th removed lymph node, the effect of CSM became marginal. The effect of N-stage on CSM could not be tested due to insufficient number of observations., Conclusions: Salvage radical prostatectomy is rarely performed and LND at salvage radical prostatectomy is performed in a minority of patients. However, LND at salvage radical prostatectomy is associated with lower CSM. Moreover, LND extent also exerts a protective effect on CSM. These observations should be considered in salvage radical prostatectomy candidates., (© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.)

Background: As recent prospective studies showed targeted biopsies (TBs) to be superior to systematic biopsies (SBs), magnetic resonance imaging (MRI) is gaining wider acceptance in the diagnostic setup of prostate cancer (PCa)., Objective: To examine the performance of MRI/ultrasound fusion-guided TB in combination with SB in the detection of PCa in patients with and without prior biopsy., Design, Setting, and Participants: A total of 219 men undergoing combined transrectal TB and 12-core SB from February 2014 to November 2018 were analysed. For all patients showing a suspicion of PCa in multiparametric MRI, TB was performed using fusion imaging with real-time virtual sonography., Outcome Measurements and Statistical Analysis: Cancer detection rates (CDRs) and significant CDRs for TB, SB, and TB+SB were analysed. Further stratification was performed for a number of previous biopsy sessions and Prostate Imaging Reporting and Data System (PI-RADS) score. Significant PCa was defined as any PCa with Gleason score ≥3+4., Results and Limitations: Of all, 141 patients were biopsy naïve, while 78 patients had at least one prior biopsy. Median prostate-specific antigen (PSA) level prior to biopsy was 8.4ng/ml (interquartile range 5.5-11.8ng/ml). The overall CDR was 63.5% (139/219), while the PI-RADS-dependent CDRs for the combination of TB+SB were 29.1%, 67.7%, and 86.2% for patients with PI-RADS 3, 4, and 5, respectively. Looking at TB or SB alone, CDRs were 55.7% and 57.5%. The overall CDR for significant PCa was 51.6%. (18.2%, 50.5%, and 81.5% for PI-RADS 3, 4, and 5, respectively). CDRs were significantly higher for biopsy-naïve patients (65.2% vs 67.4% vs 71.6% for TB vs SB vs TB+SB) than for patients with one previous negative biopsy (38.2% vs 43.6% vs 50.9% for TB vs SB vs TB+SB; all p<0.01)., Conclusions: Multiparametric MRI can raise the CDR in patients with and without biopsies performed earlier. With higher PI-RADS lesions, the risk of harbouring PCa increases. Combining TB with SB further improved the diagnostic accuracy in biopsy-naïve patients and after one previous negative biopsy., Patient Summary: Multiparametric magnetic resonance imaging before prostate biopsy increases cancer detection rates in biopsy-naïve patients and patients with a previous negative biopsy. The combination of targeted biopsy with systematic biopsy improved the diagnostic accuracy in biopsy-naïve patients and after one previous negative biopsy., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Neurovascular bundle (NVB) preservation (NVBP) and surgical margin status are the main intraoperative factors influencing functional and oncologic outcomes in patients with prostate cancer undergoing radical prostatectomy (RP)., Objective: To test the impact of implementing the intraoperative frozen section technique (IFST) during NVBP on the frequency of NVB procedures and its effect on positive surgical margins (PSMs)., Design, Setting, and Participants: We relied on an institutional tertiary-care center database to identify patients who underwent RP (January 2014-October 2018). Until October 2017, decision for NVBP was taken based on preoperative magnetic resonance imaging, clinical characteristics, and nomograms, without the IFST. After November 2017, all patients received bilateral NVBP with the IFST, to check for a PSM in the area of the NVB. If a PSM occurred, a secondary resection of the respective NVB was performed., Outcome Measurements and Statistical Analysis: PSM and NVB procedures were assessed. Subgroup analyses focused on pathologic tumor stages., Results and Limitations: Overall, 346 patients were identified. Of these patients, 54.9% (n=190) versus 45.1% (n=156) underwent RP without versus with the IFST. By using the IFST during NVBP, the PSM decreased from 29.5% to 15.4% (p=0.003) in the entire cohort (14.6% vs 8.6% in pT2; 47.1% vs 29.4% in pT3). Conversely, NVBP increased from 55.3% to 95.5% (p<0.001) in the entire cohort (68.9% vs 99.0% in pT2; 39.1% vs 88.2% in pT3). In multivariable logistic regressions, IFST use was an independent predictor of PSMs (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.30-0.98; p=0.047) and NVBP (OR: 5.60, 95% CI: 3.10-10.51; p<0.001) after controlling for patient and tumor characteristics., Conclusions: Implementation of the IFST during NVBP resulted in more frequent NVBP and was associated with a lower PSM, compared with RP without the IFST. Therefore, the IFST should be performed, if available., Patient Summary: The intraoperative frozen section technique (IFST) during preservation of neurovascular bundles (NVBP) should be offered to patients who undergo radical prostatectomy. The IFST can reduce positive margin rates and increase the rate of NVBP., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: A considerable number of prostate cancer (PCa) patients eligible for expectant management receive definitive treatment. We aimed to investigate the hospital-level contribution to overtreatment in the United States., Methods: Using the National Cancer Database we identified two nonoverlapping cohorts: (1) men with a life expectancy <10 years harbouring low or intermediate risk PCa (2) men with life expectancy ≥10 years with low-risk PCa. Multivariable mixed models with patient characteristics as fixed and hospital-level intercept as random effect were used to assess the hospital-level risk-adjusted probability of definitive treatment in both groups. Pearson's correlation coefficient was calculated to investigate the correlation between the hospitals probabilities of treating patients of both cohorts., Results: We found 33,431 men with a life expectancy <10 years and 122,514 men with a life expectancy ≥10 years and low-risk PCa. In the latter, the probability of treatment ranged from 29.0% in the bottom to 90.0% in the top decile and from 35.0% to 88.0% for men with a life expectancy <10 years. Age and race were independent predictors of low-value treatment in both cohorts. The correlation between 1,225 hospitals treating men of both cohorts was strong (Pearson's r = 0.66, P < 0.001)., Conclusion: There is wide hospital-level variability in low-value treatment of men with limited life expectancies and low-risk PCa. Hospitals more likely to treat men with limited life expectancies were more likely to treat men with low-risk PCa and vice versa. Identifying drivers and modifying practice at these hospitals may represent an effective tool for reducing overtreatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: We investigated the quality of care at minority serving hospitals compared to other institutions for men with localized intermediate and high risk prostate cancer., Materials and Methods: Using the National Cancer Database we identified 536,539 men 40 years old or older who presented with localized intermediate and high risk prostate cancer in the United States between 2004 and 2015. Institutions were ranked according to the proportion of black and Hispanic patients treated at a given institution, and the top decile institutions were defined as minority serving hospitals. We used multivariable analyses to characterize the association between minority serving hospitals and 3 end points, including receipt of definitive treatment, time to definitive treatment and receipt of androgen deprivation therapy in young (65 years or younger) and healthy (no comorbidity) men treated with external beam radiation therapy., Results: A total of 162 and 1,168 hospitals were defined as minority and nonminority serving hospitals, respectively. On multivariable analyses treatment at minority serving hospitals was associated with decreased odds of receiving definitive treatment (adjusted OR 0.73, 95% CI 0.62-0.85, p <0.001). Adjusted mean ± SE time to treatment was significantly longer at minority serving hospitals compared to nonminority serving hospitals (4.9 ± 2.2 days, p = 0.024). Among young and healthy men there was no association between treatment at a minority serving hospital and receipt of androgen deprivation therapy in conjunction with external beam radiation (AOR 0.90, 95% CI 0.75-1.09, p = 0.291)., Conclusions: Treatment at a minority serving hospital was associated with lower odds of receiving definitive therapy and longer time to definitive therapy for localized intermediate and high risk prostate cancer despite adjustment for race. This suggests that some racial disparities in prostate cancer may be explained by the sites at which racial and/or ethnic minorities receive care.

Background: Racial differences in prostate cancer (PCa) outcomes in the United States may be due to differences in tumor biology and race-based differences in access and treatment. We designed a study to estimate the relative contribution of these factors on Black/White disparities in overall survival (OS) in advanced PCa., Methods: We identified Black and White men aged ≥ 40 years with metastatic or locally advanced PCa (cN+ cM+ and/or T3/4) between 2004 and 2010 using the National Cancer Database. We employed sequential propensity score weighting procedures to generate simulated cohorts of Black and White patients with equal demographics, access to care, treatment, and tumor characteristics. Adjusted survival analyses were used to compare survival in these simulated cohorts. The changes in relative survival after each weighting procedure were used to infer the contribution of each set of variables on the excess risk of mortality in Blacks., Results: In total, 35,611 men met inclusion criteria, 5927 (16.77%) of whom were Black. Survival was significantly worse for Black men after adjusting for demographics and comorbidities (hazard ratio (HR) 1.27, 95%-confidence interval (95%-CI) 1.2-1.34, p < 0.001). After simulating equal access to care, there was no significant difference in survival between races (HR 1.04, 95%-CI 0.97-1.12, p = 0.276), despite worse tumor characteristics in Blacks. After simulating equal treatment and equivalent tumor characteristics, Black men had a better survival than Whites (HR 0.93, 95%-CI 0.86-1.01, p = 0.071 and HR 0.92, 95%-CI 0.84-1.00, p = 0.043, respectively). Overall, access-related variables explained 84.7% of the excess risk of death in Black men., Conclusion: Our analysis of men with advanced PCa revealed worse OS among Blacks. However, when access to care, treatment, and cancer characteristics are accounted for, Black race was associated with better OS. These findings suggest that initiatives to improve access to care may represent an effective tool to reduce disparities in PCa outcomes.

Objectives: To re-evaluate safety and efficacy of transperineal reanastomosis (TPRA) as a viable therapeutic option in highly recurrent anastomotic strictures (AS) after radical retropubic prostatectomy (RRP)., Methods: Retrospective analysis by standardized questionnaire inquiring for recurrence of stricture, stress urinary incontinence (SUI), sexual function, satisfaction, and changes in quality of life (QoL) was performed in all patients undergoing TPRA. Validated questionnaires (ICIQ-UI, EQ-5D, and IPSS) were included., Results: Median follow-up was 45.0 months. The average number of prior operations was 4.69. Success rate was 87% (20/23). Three recurrences were successfully treated via endoscopic means. All patients had urinary incontinence pre-op and post-op. Implantation of an artificial urinary sphincter (AUS) has been performed successfully in 73.9% (17/23). Rate of complications was low (8.7%; 2/23, Clavien-Dindo Grade II + III). EQ-5D-VAS showed a good general state of health (73.5/100). An improvement in QoL was noted in 63.6% (14/22) and patient satisfaction was high (72.7%; 16/22)., Conclusions: This extended follow-up confirms the initial results for TPRA as an excellent treatment option for highly recurrent AS after RRP. Postoperative SUI as a consequence of transsphincteric urethral mobilization can be satisfactorily treated by the implantation of AUS. In case of AS recalcitrant to endoscopic treatment, the described procedure-even though technically challenging-represents a valuable treatment option.

Objectives: To analyze the frequency of incidental prostate cancer (PC) at radical cystoprostatectomy (RC) for urothelial carcinoma of the bladder (UCB) and its association with survival outcomes in an international cohort., Patients and Methods: In this retrospective study, we included 2114 who underwent RC and lymphadenectomy for UCB between 1976 and 2012 male patients from seven institutions. Univariable and multivariable Cox regression models addressed the association of incidental PC with cancer-specific mortality and overall mortality after RC., Results: Overall, incidental PC was found in 513 (24.3%) patients with the lowest frequency in a Japanese center (23/164, 11.2%) and the highest frequency in a North American center (122/325, 37.5%), respectively (p < 0.001). Within a median follow up of 27 months (IQR: 50 months), 20 patients (3.9%) were diagnosed with biochemical recurrence (BCR) and none of the patients died of PC. PC pathological tumor stage was more advanced in patients experiencing BCR (p < 0.001). In multivariable Cox regression analyses adjusted for standard clinicopathologic features, incidental PC was not associated with cancer-specific (HR: 1.11, 95% CI: 0.91-1.35, p = 0.30) or overall mortality (HR: 1.06, 95% CI: 0.83-1.35, p = 0.65)., Conclusions: Incidental PC at RC for UCB is a frequent event. However, the majority of PC cases are well-differentiated and organ-confined. Presence of incidental PC shows significant geographic differences. The risk of BCR after incidental PC is low and incidental PC is not associated with survival in UCB patients treated with RC., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: To validate Caveolin-1 as an independent prognostic marker of biochemical recurrence (BCR) in a large multi-institutional cohort of patients with prostate cancer treated with radical prostatectomy (RP)., Patients and Methods: Caveolin-1 expression was evaluated by immunochemistry on a tissue microarray in 3 117 patients treated with RP for prostate cancer at five institutions. Univariable and multivariable Cox proportional hazards regression models assessed the association of Caveolin-1 status with BCR. Harrell's c-index quantified prognostic accuracy., Results: Caveolin-1 was overexpressed in 644 (20.6%) patients and was associated with higher pathological Gleason sum (P = 0.002) and lymph node metastases (P = 0.05). Within a median (interquartile range) follow-up of 38 (21-66) months, 617 (19.8%) patients experienced BCR. Patients with overexpression of Caveolin-1 had worse BCR-free survival than those with normal expression (log-rank test, P = 0.004). Caveolin-1 was an independent predictor of BCR in multivariable analyses that adjusted for the effects of standard clinicopathological features (hazard ratio 1.21, P = 0.037). Addition of Caveolin-1 in a model for prediction of BCR based on these standard prognosticators did not significantly improve the predictive accuracy of the model. In subgroup analyses, Caveolin-1 was associated with BCR in patients with favourable pathological features (pT2pN0 and Gleason score = 6; P = 0.021)., Conclusions: We confirmed that overexpression of Caveolin-1 is associated with adverse pathological features in prostate cancer and independently predicts BCR after RP, especially in patients with favourable pathological features. However, it did not add prognostically relevant information to established predictors of BCR, limiting its use in clinical practice., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Objective: To validate the impact of lymphovascular invasion (LVI) on biochemical recurrence (BCR) in patients treated with radical prostatectomy (RP) in a large multiinstitutional cohort., Material and Methods: Retrospective data from 6,678 patients treated with a RP and bilateral lymphadenectomy for prostate cancer (PC) from 8 centers were collected. The primary endpoint was BCR., Results: Overall, 767 patients (11.5%) had LVI. Patients with LVI had significantly higher Gleason scores (P = 0.01). After a median follow-up of 28 months (interquartile range: 21-44), patients with LVI had a 1.66 fold increased risk of BCR (P<0.001). The 1-, 2- and 5-year biochemical recurrence-free survival probabilities for LVI vs. no LVI were 94% vs. 97%, 91% vs. 94%, and 76% vs. 84%, respectively. On multivariable analysis that adjusted for the effects of established prognostic factors, LVI was an independent predictor of BCR (hazard ratio = 1.42, P<0.001). Adding LVI to a multivariable base model increased the discrimination by a small but significant margin (+0.2%, P = 0.0005). In subgroup analyses, LVI remained an independent predictor for BCR in patients with worse pathological features., Conclusions: About 10% of patients with localized PC have LVI on their RP specimen. We confirm that LVI is associated with features of biologic aggressive PC such as high Gleason grade and BCR after RP. Adverse further studies with strict definitions of LVI and longer follow-up periods are needed to determine the prognostic and predictive utility of LVI in the management of PC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Cigarette smoking seems to be associated with prostate cancer (PCa) incidence and mortality., Objective: To elucidate the association between pretreatment smoking status, cumulative smoking exposure, and time since smoking cessation and the risk of biochemical recurrence (BCR) of PCa in patients treated with radical prostatectomy (RP)., Design, Setting, and Participants: Retrospective analysis of 6538 patients with pathologically node-negative PCa treated with RP between 2000 and 2011. Clinicopathologic and smoking variables, including smoking status, number of cigarettes per day (CPD), duration in years, and time since smoking cessation were collected., Intervention: RP without neoadjuvant therapy., Outcome Measurements and Statistical Analysis: Univariable and multivariable Cox regression analyses assessed the association between smoking and risk of PCa BCR., Results and Limitations: Of 6538 patients, 2238 (34%), 2086 (32%), and 2214 (34%) were never, former, and current smokers, respectively. Median follow-up for patients not experiencing BCR was 28 mo (interquartile range 14-42). RP Gleason score (p=0.3), extracapsular extension (p=0.2), seminal vesicle invasion (p=0.8), and positive surgical margins (p=0.9) were comparable among the three groups. In multivariable Cox regression analysis, former smokers (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.30-2.04; p<0.001) and current smokers (HR 1.80, 95% CI 1.45-2.24; p<0.001) had a higher risk of PCa BCR compared with non-smokers. Smoking cessation for ≥10 yr mitigated the risk of BCR in multivariable analyses (HR 0.96, 95% CI 0.68-1.37; p=0.84). In multivariable analysis, no significant association between cumulative smoking exposure and risk of BCR could be detected. Limitations of the study include the retrospective design and potential recall bias regarding smoking history., Conclusion: Smoking seems to be associated with a higher risk of PCa BCR after RP. The effects of smoking appear to be mitigated by ≥10 yr of cessation. Smokers should be counseled regarding the detrimental effects of smoking on PCa prognosis., Patient Summary: We investigated the effect of smoking on the risk of prostate cancer recurrence in patients with treated with surgery. We found that former smokers and current smokers were at higher risk of cancer recurrence compared to patients who never smoked; the detrimental effect of smoking was mitigated after 10 yr or more of smoking cessation. We conclude that smokers should be counseled regarding the detrimental effects on prostate cancer outcomes., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: The objective of the current study was to test generalizability and clinical value of a recently published nomogram to predict specimen-confined disease (SCD, pT2-pT3a+R0+pN0) at radical prostatectomy (RP) in patients with clinical high-risk prostate cancer (HRPCa). The nomogram allows improved decision making with curative intent within this heterogeneous patient cohort, which is important, as RP in patients with clinical HRPCa remains a topic of controversy., Methods: We externally validated the nomogram in 1,669 men with clinical HRPCa who underwent RP and extended pelvic lymph node dissection between 1992 and 2011. A Kaplan-Meier analysis to estimate 5- and 10-year biochemical recurrence-free survival was performed. To investigate the SCD model׳s performance, the previously reported regression coefficients of the SCD nomogram were applied. Within loess calibration plots, the extent of overestimation or underestimation was graphically explored. Finally, decision curve analysis (DCA) to assess the clinical value of the SCD nomogram was performed., Results: Overall, 49% of men showed SCD after RP. The 5- and 10-year biochemical recurrence rates for men with SCD were 66% and 56%, respectively, vs. 32% and 20%, respectively, for men without SCD (log-rank test P<0.001). External validation demonstrated comparable accuracy in relation to accuracy derived from internal validation (68.1% vs. 72.0%). Calibration was suboptimal, showing a tendency to underestimate SCD probability. In DCA, the nomogram׳s usage was associated with a clinical net benefit relative to both treating all and none., Conclusions: Within our cohort, the nomogram׳s use was associated with a clinical net benefit according to DCA. However, one-third of men were falsely classified as having SCD or non-SCD. Nevertheless, in the absence of superior tools, the SCD nomogram represents a useful clinical decision aid., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Recent studies indicate frequent early PSA retesting unrelated of men's baseline PSA, which increases the harms of early detection especially among men with low PSA. The current study investigates the PCa incidence among men with baseline PSA <1.0 ng ml(-1) in order to adjust retest intervals for more targeted early detection. Between 1998 and 2012, 2,416 men with baseline PSA <1.0 ng ml(-1) were prospectively observed. Primary endpoint was PCa diagnosis. Negative predictive value (NPV) and number needed to screen (NNS) to detect one PCa were calculated. During a median follow-up time of 12.1 years, 54 (2.2%) PCa were diagnosed with n = 26 (48.1%) among men with baseline PSA of 0.75 ≤ 1.0 ng ml(-1) (upper baseline PSA quartile). The 10-year probability of being diagnosed with PCa increased significantly from 0.19% (baseline PSA < 0.40 ng ml(-1) ) to 2.0% (baseline PSA 0.40 ≤ 0.56 ng ml(-1) ), 2.5% (baseline PSA 0.56 ≤ 0.75 ng ml(-1) ) over 4.4% (baseline PSA 0.75 ≤ 1.0 ng ml(-1) ) (all p values <0.0001), respectively. The frequency of Gleason ≥7 PCa increased from 1 (0.17%) to 8 (1.4%), 5 (0.8) over 11 (1.8%) in these groups. The 8-year NPV for Gleason ≥ 7 PCa were 99.8 (baseline PSA < 0.40 ng ml(-1) ), 99.8 (baseline PSA 0.40 ≤ 0.56 ng ml(-1) ), 100 (baseline PSA 0.56 ≤ 0.75 ng ml(-1) ) and 99.5 (baseline PSA 0.75 ≤ 1.0 ng ml(-1) ), respectively. During 12 years, the numbers were 99.8, 98.6, 99.2, and 98.2, respectively. Therefore, due to the very low rate of Gleason ≥ 7 PCa, further screening might be omitted in men with baseline PSA < 0.4 ng ml(-1) . Between 0.4 and 1.0 ng ml(-1) , an 8-year interval can be discussed., (© 2015 UICC.)

Objective: Several smaller single-center studies have reported a prognostic role for Ki-67 labeling index in prostate cancer. Our aim was to test whether Ki-67 is an independent prognostic marker of biochemical recurrence (BCR) in a large international cohort of patients treated with radical prostatectomy (RP)., Methods: Ki-67 immunohistochemical staining on prostatectomy specimens from 3,123 patients who underwent RP for prostate cancer was retrospectively performed. Univariable and multivariable Cox regression models were used to assess the association of Ki-67 status with BCR., Results: Ki-67 positive status was observed in 762 (24.4 %) patients and was associated with lymph node involvement (LNI) (p = 0.039). Six hundred and twenty-one (19.9 %) patients experienced BCR. The estimated 3-year biochemical-free survivals were 85 % for patients with negative Ki-67 status and 82.1 % for patients with positive Ki-67 status (log-rank test, p = 0.014). In multivariable analysis that adjusted for the effects of age, preoperative PSA, RP Gleason sum, seminal vesicle invasion, extracapsular extension, positive surgical margins, lymphovascular invasion, and LNI, Ki-67 was significantly associated with BCR (HR = 1.19; p = 0.019). Subgroup analysis revealed that Ki-67 is associated with BCR in patients without LNI (p = 0.004), those with RP Gleason sum 7 (p = 0.015), and those with negative surgical margins (p = 0.047)., Conclusion: We confirmed Ki-67 as an independent predictor of BCR after RP. Ki-67 could be particularly informative in patients with favorable pathologic characteristics to help in the clinical decision-making regarding adjuvant therapy and optimized follow-up scheduling.

Purpose: We evaluated stricture-free survival and functional outcomes of buccal mucosa graft urethroplasty in patients with urethral stricture disease after radiotherapy., Materials and Methods: We reviewed our urethroplasty database for patients with a radiotherapy history who underwent buccal mucosa graft urethroplasty between January 2009 and October 2013. We reviewed patient charts and the institutional, standardized, nonvalidated questionnaires administered to each patient postoperatively. Study end points included 1) the success rate, 2) continence status, 3) erectile function and 4) patient satisfaction postoperatively. Success was defined as stricture-free survival., Results: Of 38 men included in the study prostate cancer was the most common indication for radiotherapy in 35 (92.1%). External beam radiotherapy was performed in 24 cases (64.9%), brachytherapy was done in 8 (21.6%) and a combination of the 2 treatments was performed in 6 (13.5%). Strictures were in the bulbar/bulbomembranous urethra and had a median length of 3.0 cm (range 1.0 to 8.0). The overall success rate was 71.1% at a median followup of 26.5 months (range 1.0 to 50.0). Median time to stricture recurrence was 17.0 months (range 3.0 to 44.0). De novo urinary incontinence was observed in 4 patients (10.5%). Erectile function remained mostly unchanged compared to preoperative status. Study limitations include the small sample size and the lack of validated questionnaires., Conclusions: At short-term to mid-term followup the success rate of ventral onlay buccal mucosa graft urethroplasty in patients with radiotherapy history seems acceptable. However, patients must be counseled about the increased risk of urinary incontinence. Longer followup is warranted to address long-term outcomes., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

The debate of prostate cancer (PCa) screening has been shaped over decades. There is a plethora of articles in the literature supporting as well as declining prostate-specific antigen (PSA) screening. Does screening decrease PCa mortality? With the long-term results of the European Randomized Study of Screening for Prostate (ERSPC) the answer is clearly YES. It moves! However, in medicine there are no benefits without any harm and thus, screening has to be performed in targeted and smart way-or in other words-in a risk-adapted fashion when compared with the way it was done in the past. Here, we discuss the main findings of the ERSPC trials and provide insights on how the future screening strategies should be implemented.

Objectives: The objectives of the study were to describe a novel score (safe-R), combining information on surgical margin status (SM) and extend of nerve-sparing (NS) applicable for all patients undergoing radical prostatectomy (RP), and to test the impact of our frozen-section navigated nerve-sparing approach (NeuroSAFE) on safe-R score., Methods: We retrospectively analyzed 9,635 RPs performed at our center between 2002 and 2011. Of these, 47 % were conducted with NeuroSAFE. Proportions of NS and SM status were assessed. Subsequently, a score for oncological safe NS (safe-R) was developed; Safe-R was categorized as 3 (for negative SM and bilateral NS), 2 (for negative SM and unilateral NS), 1 (for negative SM without NS), and 0 (for patients with positive SM), respectively. The impact of NeuroSAFE on safe-R was analyzed by chi-square test and confirmed by multinomial logistic regression, adjusting for preoperative risk factors., Results: Applying NeuroSAFE resulted in enhanced safe-R score, indicating lower rates of positive SM and higher rates of NS, across all risk categories (all p < 0.001). For example in high-risk patients, NeuroSAFE resulted in lower proportions of safe-R 0 (27.6 vs. 33.6 %) and higher proportions of safe-R 3 (32.4 vs. 17.1 %, p < 0.001). Linkage between the NeuroSAFE approach and safe-R was confirmed after multinomial logistic adjustment for preoperative risk factors. All results were confirmed in a propensity-matched cohort (matched for preoperative risk factors and year of surgery, data not shown)., Conclusion: Safe-R represents a novel tool to assess and report on oncological safe nerve-sparing in RP. NeuroSAFE is associated with enhanced safe-R scores.

Objective: To assess the prognostic role of extranodal extension (ENE) and the size of the largest lymph node (LN) metastasis in predicting early biochemical relapse (eBCR) in patients with LN metastasis after radical prostatectomy (RP)., Patients and Methods: We evaluated BCR-free survival in men with LN metastases after RP and pelvic LN dissection performed in six high-volume centres. Multivariable Cox regression tested the role of ENE and diameter of largest LN metastasis in predicting eBCR after adjusting for clinicopathological variables. We compared the discrimination of multivariable models including ENE, the size of largest LN metastasis and the number of positive LNs., Results: Overall, 484 patients were included. The median (interquartile range, IQR) follow-up was 16.1 (6-27.5) months. The median (IQR) number of removed LNs was 10 (4-14), and the median (IQR) number of positive LNs was 1 (1-2). ENE was present in 280 (58%) patients, and 211 (44%) had their largest metastasis >10 mm. Patients with ENE and/or largest metastasis of >10 mm had significantly worse eBCR-free survival (all P < 0.01). On multivariable analysis, number of positive LNs (≤2 vs >2) and the diameter of LN metastasis (≤10 vs >10 mm), but not ENE, were significant predictors of eBCR (all P < 0.003). ENE and diameter of LN metastasis increased the area under the curve of a baseline multivariable model (0.663) by 0.016 points., Conclusions: The diameter of the largest LN metastasis and the number of positive LNs are independent predictors of eBCR. Considered together, ENE and the diameter of the largest LN metastasis have less discrimination than the number of positive LNs., (© 2013 The Authors. BJU International © 2013 BJU International.)

Background: Nodal metastasis is the strongest risk factor of disease recurrence in patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP)., Objective: To develop a model that allows quantification of the likelihood that a pathologically node-negative patient is indeed free of nodal metastasis., Design, Setting, and Participants: Data from patients treated with RP and pelvic lymph node dissection (PLND; n=7135) for PCa between 2000 and 2011 were analyzed. For external validation, we used data from patients (n=4209) who underwent an anatomically defined extended PLND., Intervention: RP and PLND., Outcome Measurements and Statistical Analysis: We developed a novel pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative based on the number of examined nodes and the patient's characteristics., Results and Limitations: In the development and validation cohorts, the probability of missing a positive node decreases with an increasing number of nodes examined. Whereas in pT2 patients, a 90% pNSS was achieved with one single examined node in both the development and validation cohort, a similar level of nodal staging accuracy was achieved in pT3a patients by examining five and nine nodes, respectively. The pT3b/T4 patients achieved a pNSS of 80% and 70% when 17 and 20 nodes in the development and validation cohort were examined, respectively. This study is limited by its retrospective design and multicenter nature. The number of nodes removed was not directly correlated with the extent/template of PLND., Conclusions: Every patient needs PLND for accurate nodal staging. However, a one-size-fits-all approach is too inaccurate. We developed a tool that indicates a node-negative patient is indeed free of lymph node metastasis by evaluating the number of examined nodes, pT stage, RP Gleason score, surgical margins, and prostate-specific antigen. This tool may help in postoperative decision making., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To date, evidence on active surveillance (AS) is restricted to protocol-based studies. Conversely, practice patterns outside of such protocols are unknown. The aim of this study was to capture the current AS treatment patterns for localized prostate cancer in patients managed by office-based urologists compared to patients treated at a tertiary care center., Methods and Materials: Two prospective cohorts were investigated: 361 AS arm patients of the German Hormonal treatment, Active surveillance, Radiation therapy, OP, Watchful waiting (HAROW) study, an observational health service study and 387 protocol-based AS patients treated at the Department of Urology of the Kantonsspital Aarau, Switzerland were included. Observational non-protocol HAROW versus on-protocol Kantonsspital Aarau (KSA) was compared, and active-treatment-free survival represented the primary outcome., Results: Study population of the observational HAROW versus tertiary care protocol-based KSA cohorts differed statistically significantly regarding age (p < 0.001) and proportion of patients meeting the Chism criteria (p < 0.001). In stratified analyses, AFTS at 1 and 2 years was, respectively, 87.7 % (95 % CI 84.0-91.7) and 75.0 % (95 % CI 69.7-80.8) in HAROW patients compared to 90.8 % (95 % CI 87.8-93.9) and 75.3 % (95 % CI 70.7-80.1) for patients in the KSA cohort (p = 0.97)., Conclusion: We demonstrate significant differences in terms of AS inclusion, surveillance and discontinuation criteria between patients managed by office-based urologists compared to their tertiary care counterparts. Interestingly, the risk of deferred active therapy was equally moderate for both groups in the short-term follow-up.

Purpose: The impact of diabetes mellitus (DM) and metformin use on biochemical recurrence (BCR) in patients treated with radical prostatectomy (RP) remains controversial., Methods: We retrospectively evaluated 6,863 patients who underwent RP for clinically localized PC between 2000 and 2011. Univariable and multivariable Cox regression models addressed the association of DM and metformin use with BCR., Results: Overall, 664 patients had a diagnosis of DM from which 287 (43 %) were on metformin and 377 (57 %) were on anti-diabetics other than metformin. DM and metformin were not associated with any clinicopathologic features (p values >0.05). Within a median follow-up of 25 months (interquartile range 35 months), 774 (11.3 %) patients experienced BCR. Actuarial 5-year biochemical-free survival was 83 % for non-diabetic, 79 % for diabetic patients without metformin use, and 85 % for diabetic patients with metformin use (log rank p = 0.17). In uni- and multivariable Cox regression analyses with the non-diabetic group as referent, DM without metformin use (HR = 0.99; 95 % CI 0.75-1.30, p = 0.65) and DM with metformin use (HR = 0.84, 95 % CI 0.58-1.22, p = 0.36) were not associated with BCR after RP. A subgroup analysis stratified by nodal status, surgical margins, tumor stage, and Gleason sum did not reveal any significant association between DM, use of metformin and risk of BCR., Conclusions: We found no association between DM or metformin use and cancer-specific features or BCR in patients treated with RP. The effect of DM and metformin on complications, wound healing and overall survival needs to be assessed in similar cohorts.

Objective: To address the biochemical and functional outcomes after radical prostatectomy (RP) of men aged <50 years in a large European population., Patients and Methods: Among 13,268 patients who underwent RP for clinically localised prostate cancer at our centre (1992-2011), 443 (3.3%) men aged <50 were identified. Biochemical recurrence (BCR) and functional outcomes (International Index of Erectile Function [IIEF-5], use of pads), were prospectively evaluated and compared between men aged <50 years and older patients., Results: Men aged <50 years were more likely to harbour D'Amico low-risk (49.4 vs 34.9%, P < 0.001), organ-confined (82.6 vs 69.4%, P < 0.001) and low-grade tumours (Gleason score <7: 33.1 vs 28.7%, P < 0.001). Multivariate Cox regression analysis showed that age <50 years (hazard ratio 0.99; confidence interval 0.72-1.31; P = 0.9) was not a predictor of BCR. Urinary continence was more favourable in younger patients, resulting in continence rates of 97.4% vs 91.6% in most recent years (2009-2011) for patients aged <50 vs ≥50 years. After RP, a median IIEF-5 drop of 4 points in younger men vs 8 points in older patients was recorded (P < 0.001). Favourable recovery of urinary continence and erectile function in patients aged <50 years compared with their older counterparts was confirmed after multivariable adjustment., Conclusion: Men aged <50 years diagnosed with localised prostate cancer should not be discouraged from RP, as the postoperative rates of urinary incontinence and erectile dysfunction are low and probability of BCR-free survival at 2 and 5 years is high., (© 2013 The Authors. BJU International © 2013 BJU International.)

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) may play important roles in prostate cancer (PCa) progression. Specifically, LH expression in PCa tissues has been associated with metastatic disease with a poor prognosis, while FSH has been shown to stimulate prostate cell growth in hormone-refractory PCa cell lines. Gonadotropin-realizing hormone (GnRH) analogues are common agents used for achieving androgen deprivation in the treatment for PCa. GnRH analogues include LH-releasing hormone (LHRH) agonists and GnRH antagonists, both of which exhibit distinct mechanisms of action that may be crucial in terms of their overall clinical efficacy. LHRH agonists are typically used as the primary therapy for most patients and function via a negative-feedback mechanism. This mechanism involves an initial surge in testosterone levels, which may worsen clinical symptoms of PCa. GnRH antagonists provide rapid and consistent hormonal suppression without the initial surge in testosterone levels associated with LHRH agonists, thus representing an important therapeutic alternative for patients with PCa. The concentrations of testosterone and dihydrotestosterone are significantly reduced after treatment with both LHRH agonists and GnRH antagonists. This reduction in testosterone concentrations to castrate levels results in significant, rapid, and consistent reductions in prostatic-specific antigen, a key biomarker for PCa. Evidence suggests that careful maintenance of testosterone levels during androgen deprivation therapy provides a clinical benefit to patients with PCa, emphasizing the need for constant monitoring of testosterone concentrations throughout the course of therapy.