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Introduction: Obesity might negatively affect prostate cancer (PCa) outcomes. However, evidence according to the associations between obesity and metastases-free survival after radical prostatectomy (RP) is still inconsistent.Methods: We relied on PCa patients treated with RP at the Martini-Klinik Prostate Cancer Center between 2004 and 2015. First, multivariable Cox regression analyses examined the impact of obesity on metastases after RP. Last, in a propensity score matched cohort, Kaplan-Meier analyses assessed metastases-free survival according to body mass index (kg/m2) (BMI) strata (≥ 30 vs. < 25).Results: Of 13,667 individuals, 1990 (14.6%) men were obese (BMI ≥ 30). Median follow-up was 36.4 month (IQR 13.3-60.8). Obese patients were less likely to exhibit metastases after RP (HR 0.7, 95% CI 0.5-0.97, p = 0.03). Similarly, after propensity score adjustment, obesity was associated with increased metastases-free survival (log rank p = 0.001).Conclusion: We recorded the obesity paradox phenomenon in PCa patients. In particular, high BMI (≥ 30) was associated with decreased risk of metastases after RP, despite an increased risk being anticipated. Whether statin use might have affected the results was not assessed. Further research is needed to unravel the controversially debated association between obesity and PCa. [ABSTRACT FROM AUTHOR]

Objective To retrospectively assess the rate of high-grade primary Gleason upgrading ( HGPGU) to primary Gleason pattern 4 or 5 in a contemporary cohort of patients with D'Amico low-risk prostate cancer including those who fulfilled Prostate Cancer Research International Active Surveillance ( PRIAS) criteria, and to develop a tool for HGPGU prediction. HGPGU is a contraindication in most active surveillance ( AS) and focal therapy protocols. Patients and Methods In all, 10 616 patients with localised prostate cancer were treated at a high-volume European tertiary care centre from 2010 to 2015 with radical prostatectomy. Analyses were restricted to 1 819 patients with D'Amico low-risk prostate cancer (17.1%) with prostate-specific antigen ( PSA) levels of <10.0 ng/mL, cT1c- cT2a and Gleason score ≤6, and were repeated within 772 of the men (7.3%) who fulfilled the PRIAS criteria for AS ( PSA level of ≤10 ng/mL, T1c-T2, Gleason score ≤6, PSA density ( PSAD) of <0.2 ng/mL2, ≤2 positive cores). Uni- and multivariable logistic regression models were fitted, testing predictors of HGPGU. The final logistic regression model was based on the most informative variables. Results There was HGPGU in 88 (4.8%) patients with D'Amico low-risk prostate cancer and in 32 (4.1%) of the subgroup who were PRIAS eligible. Multivariable analysis predicting HGPGU for the patients with D'Amico low-risk yielded three independent predictors: age, PSAD, and clinical tumour stage ( P = 0.008, P = 0.005 and P = 0.021, respectively). Within the same patients, the model using all vs the most informative variables resulted in area under the curves ( AUCs) of 69.2% and 68.3%, respectively. Multivariable analysis of those who were PRIAS eligible, yielded age and number of positive cores as independent predictors of HGPGU ( P = 0.002 and P = 0.049, respectively; AUC 64.9%). Conclusions The low accuracy (invariably <70%) for HGPGU prediction in both patients with D'Amico low-risk prostate cancer and PRIAS eligibility indicates that these variables have poor predictive ability in contemporary patients. Despite HGPGU being a rare phenomenon, it may have life threatening implications and consequently alternatives such as biomarkers, genetic markers, or imaging modalities at re-biopsy are needed. [ABSTRACT FROM AUTHOR]

Purpose: Unfavorable prostate cancer (PCa) disease at final pathology affects at least 10 % of D'Amico low-risk patients. Thus, conservative therapies including active surveillance may be wrongfully applied. The purposes were to assess the rate of upstaging in a contemporary cohort of D'Amico low-risk PCa patients and to develop and externally validate a nomogram as upstaging prediction tool in two European cohorts. Methods: Analyses were restricted to 2007 patients who harbored low-risk PCa at ≥10-cores initial biopsy according to D'Amico classification (PSA <10.0 ng/ml, Gleason score <7 and clinical stage ≤T2a). Patients underwent radical prostatectomy at a high-volume center in Hamburg, Germany, from 2010 to 2015. The Hamburg cohort was randomly divided into development ( n = 1338) and validation cohorts ( n = 669). The development cohort was used to devise a nomogram predicting upstaging, defined as presence of ≥pT3 and/or lymph node invasion. The nomogram was externally validated in two European validation cohorts (Hamburg, n = 669; Milan, n = 465). Results: Upstaging was observed in 187/1338 (14.0 %) of low-risk patients. In multivariable models, four of ten tested variables achieved independent predictor status: age (OR 1.07, 95 % CI 1.04-1.09), PSA (OR 1.21, 95 % CI 1.12-1.31), prostate volume (OR 0.97, 95 % CI 0.96-0.98) and percentage of positive cores (OR 1.02, 95 % CI 1.01-1.03). In external validation, the nomogram demonstrated 70.8 % (Hamburg) and 70.0 % (Milan) accuracy, respectively, with excellent concordance between predicted and observed values. Conclusions: Our proposed nomogram is capable to accurately identify D'Amico low-risk patients at risk of upstaging, utilizing four routinely available clinical variables, age, PSA, prostate volume and percentage of positive biopsy cores. Patient summary: Unfavorable prostate cancer disease at final pathology affects at least 10 % of D'Amico low-risk patients. Thus, we developed and externally validated a new nomogram based on contemporary low-risk prostate cancer patients to accurately identify D'Amico low-risk patients at risk of upstaging. It utilizes four routine variables, age, PSA, prostate volume and percentage of positive biopsy cores. [ABSTRACT FROM AUTHOR]

Objective: To examine characteristics of robot-assisted (RARP) and open radical prostatectomy (ORP) patients. Patients and Methods: We relied on the Surveillance, Epidemiology, and End Results-Medicare-linked database and focused on prostate cancer patients between 2008 and 2009. In multivariable logistic regression analyses, we predicted RARP. Results: Of 5,915 patients, 3,476 (58.8%) underwent RARP and 2,439 (41.2%) ORP. Patients within intermediate (OR 1.4, p = 0.01) or highest (OR 1.5, p = 0.02) education stra- ta and those treated by surgeons with a high volume (OR 2.2, p < 0.001) were more likely to undergo RARP. Conversely, those residing in rural areas (OR 0.7, p = 0.005) and those with clinical stage T2 or higher (OR 0.7, p = 0.006) were less likely to undergo RARP. Additionally, patients from the Southwest were less likely to undergo RARP (OR 0.4, p < 0.001), but those from the Northern Plains were more likely to undergo RARP (OR 1.4, p = 0.02) than their counterparts from the East. Finally, RARP patients were neither younger nor healthier than ORP patients. Conclusions: Several patient characteristics such as education, region of residence and population density affect the likelihood of RARP vs. ORP treatment. Similarly, clinical stage and surgeon characteristics also affect the assignment to one or other treatment modality. [ABSTRACT FROM AUTHOR]

Objective: To examine the characteristics of robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP) patients at a high-volume center. Patients and Methods: We relied on the Martini-Clinic database and focused on prostate cancer patients treated in 2013. Characteristics in ORP and RARP patients were assessed. In multivariable logistic regression analyses (MVA), we predicted RARP treatment. Results: Of 1,920 patients, 575 (29.9%) underwent RARP and 1,345 (70.1%) ORP. RARP patients had a lower prostate-specific antigen (PSA), and were less likely to harbor pT3b, pathological Gleason ≥ 4 + 4 or lymph node metastases (all p < 0.05). Pelvic lymph node dissection (PLND) (84.3 vs. 87.0%, p = 0.1), as well as positive surgical margins (15.5 vs. 15.7%, p = 0.7) and the nerve-sparing status (p = 0.5) were comparable between RARP and ORP. Lymph node yield (median 11 vs. 16), and median blood loss (250 vs. 700 ml) were lower at RARP (all p < 0.001). Additionally, the median operating room time was higher at RARP (215 vs. 185 min, p < 0.001). In MVA, patients with body mass index (BMI) ≥ 30 were more likely to undergo RARP (OR 1.8, 95% CI 1.3- 2.4, p < 0.001). Conversely, patients with PSA >20 ng/ml were less likely to undergo RARP (OR 0.6, 95% CI 0.4-1.0, p = 0.03). Conclusions: More favorable pathological characteristics were recorded at RARP. High BMI and low PSA were independent predictors for RARP. Treatment characteristics such as PLND rates, margin status and nerve sparing were comparable between RARP and ORP. Despite lower blood loss at RARP, a longer operating room time and lower yield of lymph nodes were recorded. [ABSTRACT FROM AUTHOR]

Objective: To analyse oncological and functional outcomes of salvage radical prostatectomy (SRP) in patients with recurrent prostate cancer and to compare outcomes of patients within and outside the European Association of Urology (EAU) guideline criteria (organ-confined prostate cancer ≤T2b, Gleason score ≤7 and preoperative PSA level <10 ng/mL) for SRP. Patients and Methods: In all, 55 patients who underwent SRP from January 2007 to December 2012 were retrospectively analysed. Kaplan-Meier curves assessed time to biochemical recurrence (BCR), metastasis-free survival (MFS) and cancer-specific survival. Cox regressions addressed factors influencing BCR and MFS. BCR was defined as a PSA level of >0.2 ng/mL and rising, continence as the use of 0-1 safety pad/day, and potency as a five-item version of the International Index of Erectile Function score of ≥18. Results: The median follow-up was 36 months. After SRP, 42.0% of the patients experienced BCR, 15.9% developed metastasis, and 5.5% died from prostate cancer. Patients fulfilling the EAU guideline criteria were less likely to have positive lymph nodes (LNs) and had significantly better BCR-free survival (5-year BCR-free survival 73.9% vs 11.6%; P = 0.001). In multivariate analysis, low-dose-rate brachytherapy as primary treatment (P = 0.03) and presence of positive LNs at SRP (P = 0.02) were significantly associated with worse BCR-free survival. The presence of positive LNs or Gleason score >7 at SRP were independently associated with metastasis. The urinary continence rate at 1 year after SRP was 74%. Seven patients (12.7%) had complications ≥III (Clavien grade). Conclusion: SRP is a safe procedure providing good cancer control and reasonable urinary continence. Oncological outcomes are significantly better in patients who met the EAU guideline recommendations. [ABSTRACT FROM AUTHOR]

Introduction: Given the growing body of literature since first description of HistoScanning™ in 2008, there is an unmet need for a contemporary review. Evidence acquisition: Studies addressing HistoScanning™ in prostate cancer (PCa) were considered to be included in the current review. To identify eligible reports, we relied on a bibliographic search of PubMed database conducted in January 2015. Evidence synthesis: Twelve original articles were available to be included in the current review. The existing evidence was reviewed according to the three following topics: prediction of final pathology at radical prostatectomy, prediction of disease stage and application at prostate biopsy. Conclusions: High sensitivity and specificity for HistoScanning™ to predict cancer foci ≥0.5 ml at final pathology were achieved in the pilot study. These results were questioned, when HistoScanning™ derived tumor volume does not correlate with final pathology results. Additionally, HistoScanning™ was not able to provide reliable staging information according to neither extraprostatic extension, nor seminal vesicle invasion prior to radical prostatectomy. Controversy data also exist according to the use of HistoScanning™ at prostate biopsy. Specifically, most encouraging results were recorded in a small patient cohort. Conversely, HistoScanning™ achieved poor prediction of positive biopsies, when relying on larger studies. Finally, the combination of HistoScanning™ and conventional ultrasound achieved lower detection rates than systematic biopsy. Currently, evidence is at best weak and questions whether HistoScanning™ might improve the detection of PCa. [ABSTRACT FROM AUTHOR]

Objectives To examine the impact of marital status on prostate cancer characteristics at radical prostatectomy and oncological outcome after surgery at a high-volume center. Methods We relied on the Martini-Clinic Prostate Cancer database and investigated 8088 prostate cancer patients treated with radical prostatectomy between January 2000 and March 2011. We analyzed differences in clinical and pathological characteristics according to marital status (married and partnership vs single). Additionally, we relied on multivariable Cox regression analyses to predict biochemical recurrence, metastases and death after radical prostatectomy. Finally, Kaplan-Meier analyses were used in a propensity score-matched cohort, adjusted for clinical and pathological characteristics, to examine differences in biochemical recurrence-free, metastases-free and overall survival according to marital status. Results According to marital status, no significant differences were recorded within clinical and pathological characteristics (all P > 0.05). The impact of marital status on biochemical recurrence (hazard ratio 1.0, 95% confidence interval 0.9-1.3, P = 0.7), metastases (hazard ratio 1.3, 95% confidence interval 0.8-2.1, P = 0.3) and death (hazard ratio 0.8, 95% confidence interval 0.4-1.6, P = 0.6) after radical prostatectomy was not significant (median follow up 48 months). Kaplan-Meier analyses recorded no significant differences for biochemical recurrence-free, metastases-free and overall survival (all log-rank P > 0.05) according to marital status. Conclusions Marital status does not affect the clinical and pathological characteristics of radical prostatectomy patients treated at a high-volume center. Furthermore, marital status does not affect biochemical recurrence-free and metastases-free survival after radical prostatectomy. [ABSTRACT FROM AUTHOR]

Background To date, no study has examined clinical, pathological, and surgical characteristics of D׳Amico low-risk patients according to active surveillance (AS) eligibility. Material and methods We relied on patients with low-risk prostate cancer, who were classified based on the D׳Amico classification, treated with radical prostatectomy (RP) between 2008 and 2013 at the Martini-Clinic Prostate Cancer Center. We assessed differences in clinical, pathological, and surgical characteristics in D׳Amico low-risk patients according to AS eligibility (prostate-specific antigen [PSA]≤10 ng/ml, Gleason score≤3+3, ≤2 positive cores,≤50% tumor content per core, and≤cT1-2a). Multivariable logistic regression analyses targeted 2 end points: (1) presence of either intermediate- or high-risk characteristics (Gleason score≥3+4 or≥pT3 or pN1) or (2) exclusive presence of high-risk characteristics (Gleason score≥4+4 or≥pT3 or pN1) at RP. Results Of 1,331 patients low-risk prostate cancer classified based on the D׳Amico classification, 825 (62%) men were eligible for AS. AS candidates were less frequently either upgraded (55% vs. 78%, P <0.001) or upstaged (8% vs. 15%, P <0.001). Similarly, at final pathology, AS candidates less frequently harbored either intermediate- or high-risk (56% vs. 78%, P <0.001), or exclusive high-risk characteristics (9% vs. 16%, P <0.001). Tumor involvement per core (>50%) (most powerful), number of positive cores, PSA values, and age were independent predictors for either intermediate- or high-risk characteristics at RP. Tumor involvement per core and PSA values were independent predictors for exclusive high-risk characteristics at RP. Conclusions D׳Amico low-risk patients did not have a homogeneous histology at RP. Especially, non-AS candidates were at a higher risk of either upgrading or upstaging at final pathology. Tumor involvement greater than 50% per core was the most powerful indicator of adverse pathology. Therefore, DʼAmico low-risk criteria are not safe enough to identify AS candidates. [ABSTRACT FROM AUTHOR]

Background Treatment of the primary, termed local therapy (LT), may improve survival in metastatic prostate cancer (mPCa) versus no local therapy (NLT). Objective To assess cancer-specific mortality (CSM) after LT versus NLT in mPCa. Design, setting, and participants Within the Surveillance, Epidemiology and End Results database (2004–2013), 13 692 mPCa patients were treated with LT (radical prostatectomy [RP] or radiation therapy [RT]) or NLT. Outcome measurements and statistical analysis Multivariable competing risk regression analyses (MVA CRR) tested CSM after propensity score matching (PSM) in two analyses, (1) NLT versus LT and (2) RP versus RT, and were complemented with interaction, sensitivity, unmeasured confounder, and landmark analyses. Results and limitations Of 13 692 mPCa patients, 474 received LT: 313 underwent RP and 161 RT. In MVA CRR, after PSM, LT ( n = 474) results in lower CSM (subhazard ratio [SHR] 0.40, 95% confidence interval [CI] 0.32–0.50) versus NLT ( n = 1896). In MVA CRR after PSM, RP ( n = 161) results in lower CSM (SHR 0.59, 95% CI 0.35–0.99) versus RT ( n = 161). Invariably, lowest CSM rates were recorded for Gleason ≤7, ≤cT3, and M1a substage. Interaction and sensitivity analyses confirmed the robustness of results, and landmark analyses rejected the bias favouring LT. A strong unmeasured confounder (HR = 5), affecting 30% of NLT patients, could obliterate LT benefit. Data were retrospective. Conclusions In mPCa, LT results in lower mortality relative to NLT. Within LT, lower mortality is recorded after RP than RT. Patients with most favourable grade, local stage, and metastatic substage derive most benefit from LT. They also derive most benefit from RP, when LT types are compared (RP vs RT). It is important to consider study limitations until ongoing clinical trials confirm the proposed benefits. Patient summary Individuals with prostate cancer that spreads outside of the prostate might still benefit from prostate-directed treatments, such as radiation or surgery, in addition to receiving androgen deprivation therapy. [ABSTRACT FROM AUTHOR]

Introduction: In men with bothersome lower urinary tract symptoms (LUTS), medical treatment usually represents the first line. We examined the patterns of medical management of benign prostatic hyperplasia (BPH) in the Montreal metropolitan area, within the context of a case control study focusing on incident prostate cancer. Methods: Cases were 1933 men with incident prostate cancer. Population controls included 1994 age-matched men. In-person interviews collected sociodemographic characteristics and medical history, including BPH diagnosis, its duration, and type of medical treatment received. Baseline characteristics were compared by the chi-square likelihood test for categorical variables and by the students t-test for continuously coded variables. Results: Overall, 1120 participants had history of BPH; of those 53.7% received medical treatment for BPH. Individuals with medically treated BPH, compared to individuals with medically untreated BPH, were older at index date [mean: 66.9 vs. 64.9 years, p<0.001)] and at diagnosis of BPH [mean: 62.3 vs. 60.3 years, p<0.001[. They also had a longer duration of BPH-history [mean: 4.7 vs. 4.0 years, p=0.02]. Regarding medical treatment, monotherapy was more often used than combination therapy [87.6% vs. 12.4%, p< 0.001]. Alpha-blockers (69.9%) were most commonly used as monotherapy, followed by 5alpha-reductase inhibitors (5ARIs) (26.6%). Alpha-blockers plus 5ARIs were the most common combination therapy (97.3%). Conclusions: Despite evidence from randomized, controlled trials for better efficacy with use of combination therapy, monotherapy consisting of alpha-blockers or 5ARI, in that order, is most frequently used. Additionally, 5ARI use was more common than previously reported (27% vs. 15%). [ABSTRACT FROM AUTHOR]

Background Limited data exist on the impact of the site of metastases on survival in patients with stage IV prostate cancer (PCa). Objective To investigate the role of metastatic phenotype at presentation on mortality in stage IV PCa. Design, setting, and participants Overall, 3857 patients presenting with metastatic PCa between 1991 and 2009, included in the Surveillance Epidemiology and End Results–Medicare database were evaluated. Outcome measurements and statistic analyses Overall and cancer-specific survival rates were estimated in the overall population and after stratifying patients according to the metastatic site (lymph node [LN] alone, bone, visceral, or bone plus visceral). Multivariable Cox regression analyses tested the relationship between the site of metastases and survival. All analyses were repeated in a subcohort of patients with a single metastatic site involved. Results and limitations Respectively, 2.8%, 80.2%, 6.1%, and 10.9% of patients presented with LN, bone, visceral, and bone plus visceral metastases at diagnosis. Respective median overall survival and cancer-specific survival were 43 mo and 61 mo for LN metastases, 24 mo and 32 mo for bone metastases, 16 mo and 26 mo for visceral metastases, and 14 mo and 19 mo for bone plus visceral metastases ( p < 0.001). In multivariable analyses, patients with visceral metastases had a significantly higher risk of overall and cancer-specific mortality versus those with exclusively LN metastases ( p < 0.001). The unfavorable impact of visceral metastases persisted in the oligometastatic subgroup. Our study is limited by its retrospective design. Conclusions Visceral involvement represents a negative prognostic factor and should be considered as a proxy of more aggressive disease in patients presenting with metastatic PCa. This parameter might indicate the need for additional systemic therapies in these individuals. Patient summary Patients with visceral metastases should be considered as affected by more aggressive disease and might benefit from the inclusion in clinical trials evaluating novel molecules. [ABSTRACT FROM AUTHOR]

Background: The benefit of intraoperative neurovascular structure–adjacent frozen section examination (NeuroSAFE) of the prostate was demonstrated in open radical prostatectomy. In da Vinci robot-assisted prostatectomy (DVP), this approach is often avoided due to suspected difficulties in harvesting the prostate, loss in pneumoperitoneum, increased blood loss, and prolonged operating room (OR) time. Objective: To provide a detailed description of the technique, feasibility, and impact of the NeuroSAFE technique on OR time, blood loss, frequency of nerve sparing (NS), and positive surgical margins (PSMs) in DVP. Design, setting, and participants: We analyzed 1570 consecutive patients undergoing DVP from 2004 to 2012. NeuroSAFE was performed in 1178 patients. Surgical procedure: The prostate was intraoperatively harvested via an extension of the camera trocar incision without undocking the robotic arms. Blood spillage from the dorsal vein complex due to the loss of pneumoperitoneum was avoided by upward traction on the transurethral catheter. After prostate removal, pneumoperitoneum was reestablished by closing the extended incision with running sutures and repositioning the optical trocar. The NeuroSAFE procedure consisted of intraoperative bilateral frozen sections covering the entire neurovascular bundles adjacent prostate surface. Outcome measurements and statistical analysis: We compared OR time, blood loss, NS frequency, and PSMs in non-NeuroSAFE versus NeuroSAFE DVP. Results and limitations: There was no significant difference in blood loss (253.5±204.4ml vs 265.8±246.7ml; p =0.49) and OR time (220min ± 51 vs 224min ± 64; p =0.22). No complications associated with specimen harvesting occurred. NS rate increased significantly with versus without NeuroSAFE (overall 97% vs 81%; pT2 99% vs 90%, pT3a 94% vs 74%, pT3b 91% vs 30). PSM rate dropped significantly with NeuroSAFE (overall 16% vs 24%; pT2 8% vs 15%, pT3a 22% vs 39%, pT3b 49% vs 67%; all p <0.05). Conclusions: We demonstrate a time-efficient and safe adaption of the NeuroSAFE technique to DVP. Patient summary: We describe a feasible and secure adaption of the neurovascular structure–adjacent frozen section examination (NeuroSAFE) procedure for da Vinci robot-assisted prostatectomy. We showed that there was no increased blood loss and operating room time. We maximized the nerve-sparing frequency and could reduce positive surgical margins even in non–organ-confined tumors. [ABSTRACT FROM AUTHOR]

Purpose: To assess adherence rates to pelvic lymph node dissection (PLND) according to National Comprehensive Cancer Network (NCCN) PLND guideline (2% or higher risk) and D'Amico lymph node invasion (LNI) risk stratification (intermediate/high risk) in contemporary North American patients with prostate cancer treated with radical prostatectomy (RP).Material and Methods: We relied on 49,358 patients treated with RP and PLND (2010-2013) in SEER database. Adherence rates were quantified and multivariable (MVA) logistic regression analyses tested for independent predictors.Results: According to NCCN PLND guideline and D'Amico LNI classification, PLND was recommended in 63.3% and 64.9% of patients, respectively. Corresponding adherence rates were 68.8% and 69.1%. Adherence rates improved from 67.3% to 71.6% and from 67.6% to 72.0%, respectively, over time. In MVA, more advanced clinical stage, higher biopsy Gleason score and higher number of positive biopsy cores predicted PLNDs that were performed below NCCN LNI nomogram risk threshold. Conversely, lower clinical stage, lower PSA and lower biopsy Gleason score predicted PLND omission in individuals with risk level above NCCN LNI nomogram risk threshold. MVA results for D'Amico classification were virtually identical.Conclusions: Adherence to NCCN PLND guideline and D'Amico LNI classification for purpose of PLND is suboptimal in SEER population-based patients treated with RP. However, adherence rates have improved over time. Patients, who did not undergo PLND despite elevated LNI risk, had more favorable PCa characteristics than the average. Conversely, patients, who underwent PLND despite low-risk, had worse PCa characteristics than the average. [ABSTRACT FROM AUTHOR]