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Summary Background The majority of patients with metastatic castration-resistant prostate cancer (mCRPC) will have disease progression of a uniformly fatal disease. mCRPC is driven by both activated androgen receptors and elevated intratumoural androgens; however, the current standard of care is therapy that targets a single androgen signalling mechanism. We aimed to investigate the combination treatment using apalutamide plus abiraterone acetate, each of which suppresses the androgen signalling axis in a different way, versus standard care in mCRPC. Methods ACIS was a randomised, placebo-controlled, double-blind, phase 3 study done at 167 hospitals in 17 countries in the USA, Canada, Mexico, Europe, the Asia-Pacific region, Africa, and South America. We included chemotherapy-naive men (aged ≥18 years) with mCRPC who had not been previously treated with androgen biosynthesis signalling inhibitors and were receiving ongoing androgen deprivation therapy, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and a Brief Pain Inventory-Short Form question 3 (ie, worst pain in the past 24 h) score of 3 or lower. Patients were randomly assigned (1:1) via a centralised interactive web response system with a permuted block randomisation scheme (block size 4) to oral apalutamide 240 mg once daily plus oral abiraterone acetate 1000 mg once daily and oral prednisone 5 mg twice daily (apalutamide plus abiraterone–prednisone group) or placebo plus abiraterone acetate and prednisone (abiraterone–prednisone group), in 28-day treatment cycles. Randomisation was stratified by presence or absence of visceral metastases, ECOG performance status, and geographical region. Patients, the investigators, study team, and the sponsor were masked to group assignments. An independent data-monitoring committee continually monitored data to ensure ongoing patient safety, and reviewed efficacy data. The primary endpoint was radiographic progression-free survival assessed in the intention-to-treat population. Safety was reported for all patients who received at least one dose of study drug. This study is completed and no longer recruiting and is registered with ClinicalTrials.gov , number NCT02257736 . Findings 982 men were enrolled and randomly assigned from Dec 10, 2014 to Aug 30, 2016 (492 to apalutamide plus abiraterone–prednisone; 490 to abiraterone–prednisone). At the primary analysis (median follow-up 25·7 months [IQR 23·0–28·9]), median radiographic progression-free survival was 22·6 months (95% CI 19·4–27·4) in the apalutamide plus abiraterone–prednisone group versus 16·6 months (13·9–19·3) in the abiraterone–prednisone group (hazard ratio [HR] 0·69, 95% CI 0·58–0·83; p Interpretation Despite the use of an active and established therapy as the comparator, apalutamide plus abiraterone–prednisone improved radiographic progression-free survival. Additional studies to identify subgroups of patients who might benefit the most from combination therapy are needed to further refine the treatment of mCRPC. Funding Janssen Research & Development.

PURPOSE The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT). Herein, we report final efficacy and safety results after unblinding and placebo-to-apalutamide crossover. METHODS Patients with mCSPC (N = 1,052) were randomly assigned 1:1 to receive apalutamide (240 mg QD) or placebo plus ADT. After unblinding in January 2019, placebo-treated patients were allowed to receive apalutamide. Efficacy end points were updated using the Kaplan-Meier method and Cox proportional-hazards model without formal statistical retesting and adjustment for multiplicity. Change from baseline in Functional Assessment of Cancer Therapy-Prostate total score was assessed. RESULTS With a median follow-up of 44.0 months, 405 OS events had occurred and 208 placebo-treated patients (39.5%) had crossed over to apalutamide. The median treatment duration was 39.3 (apalutamide), 20.2 (placebo), and 15.4 months (crossover). Compared with placebo, apalutamide plus ADT significantly reduced the risk of death by 35% (median OS not reached v 52.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P < .0001) and by 48% after adjustment for crossover (hazard ratio, 0.52; 95% CI, 0.42 to 0.64; P < .0001). Apalutamide plus ADT delayed second progression-free survival and castration resistance ( P < .0001 for both). Health-related quality of life, per total Functional Assessment of Cancer Therapy-Prostate, in both groups was maintained through the study. Safety was consistent with previous reports. CONCLUSION The final analysis of TITAN confirmed that, despite crossover, apalutamide plus ADT improved OS, delayed castration resistance, maintained health-related quality of life, and had a consistent safety profile in a broad population of patients with mCSPC.

Ureteral stenting in patients with bladder cancer may become necessary in order to protect the ureteral orifice during transurethral resection of the tumor or for relief of upper urinary tract obstruction. However, it is believed to increase metachronous upper tract urothelial carcinoma risk.We performed a systematic review and meta-analysis of studies comparing ureteral stenting versus nephrostomy or no drainage with regard to the risk of metachronous upper tract urothelial carcinoma. Records were identified through database searches and sources of grey literature up to October 2020 (PROSPERO: CRD42020178298).Five studies (3,309 individuals) were included. Overall, 278 ureteral stents were placed and 20 (7.2%) patients developed metachronous upper tract urothelial carcinoma, while 131 patients were treated with nephrostomy and 3 (2.3%) cases of metachronous upper tract urothelial carcinoma occurred. Patients treated with ureteral stents had a higher likelihood of metachronous upper tract urothelial carcinoma compared to no stents (OR: 3.49, 95% CI: 1.43-8.48, IStenting as a preventive measure after resection of tumors involving the orifice should be avoided, when possible, as it increases the risk of metachronous upper tract urothelial carcinoma. In cases of hydronephrosis, drainage with either nephrostomy or stent is recommended depending on individual patient cases as both interventions do not differ regarding metachronous upper tract urothelial carcinoma risk.

Item does not contain fulltext INTRODUCTION: We aimed to compare the outcomes of open vs robotic partial nephrectomy (PN), focusing on predictors of Trifecta failure in patients with highly complex renal masses. PATIENTS AND METHODS: We queried the prospectively collected database from the SIB International Consortium, including 507 consecutive patients with cT1-2N0M0 renal masses treated at 16 high-volume referral centres, to select those with highly complex (PADUA score ≥10) tumors undergoing PN. RT was classified as enucleation, enucleoresection or resection according to the SIB score. Trifecta was defined as achievement of negative surgical margins, no acute kidney injury and no Clavien-Dindo grade ≥2 postoperative surgical complications. Multivariable logistic regression analysis was used to assess independent predictors of Trifecta failure. RESULTS: 113 patients were included. Patients undergoing open PN (n = 47, 41.6%) and robotic PN (n = 66, 58.4%) were comparable in baseline characteristics. RT was classified as enucleation, enucleoresection and resection in 46.9%, 34.0% and 19.1% of open PN, and in 50.0%, 40.9% and 9.1% of robotic PN (p = 0.28). Trifecta was achieved in significantly more patients after robotic PN (69.7% vs. 42.6%, p = 0.004). On multivariable analysis, surgical approach (open vs robotic, OR: 2.62; 95%CI: 1.11-6.15, p = 0.027) and tumor complexity (OR for each additional unit of the PADUA score: 2.27; 95%CI: 1.27-4.06, p = 0.006) were significant predictors of Trifecta failure, while RT was not. The study is limited by lack of randomization; as such, selection bias and confounding cannot be entirely ruled out. CONCLUSIONS: Tumor complexity and surgical approach were independent predictors of Trifecta failure after PN for highly complex renal masses.

Background: To explore predictors of positive surgical margins (PSM) after robotic partial nephrectomy (PN) in a large multicenter international observational project, harnessing the Surface-Intermediate-Base (SIB) margin score to report the resection technique after PN in a standardized way. Methods: Data from consecutive patients with cT1-2N0M0 renal masses treated with PN from September 2014 to March 2015 at 16 tertiary referral centers and included in the SIB margin score International Consortium were prospectively collected. For the present study, only patients treated with robotic PN were included. Uni- and multivariable analysis were fitted to explore clinical and surgical predictors of PSMs after PN. Results: Overall, 289 patients were enrolled. Median (IQR) preoperative tumor size was 3.0 (2.3–4.2) cm and median (IQR) PADUA score was 8 (7–9). SIB scores of 0–2 (enucleation), 3–4 (enucleoresection) and 5 (resection) were reported in 53.3%, 27.3% and 19.4% of cases, respectively. A PSM was recorded in 18 (6.2%) patients. PSM rate was 4.5%, 11.4% and 3.6% in case of enucleation, enucleoresection and resection, respectively. Patients with PSMs had tumors with a higher rate of contact with the urinary collecting system (55.6% vs. 27.3%; p < 0.001) and a longer median warm ischemia time (22 vs. 16 min; p = 0.02) compared with patients with negative surgical margins, while no differences emerged between the two groups in terms of other tumor features (i.e., pathological diameter, PADUA score). In multivariable analysis, only enucleoresection (SIB score 3–4) versus enucleation (SIB score 0–2) was found to be an independent predictor of PSM at final pathology (HR: 2.68; 95% CI: 1.25–7.63; p = 0.04), while resection (SIB score 5) was not. Conclusions: In our experience, enucleoresection led to a higher risk of PSMs as compared to enucleation. Further studies are needed to assess the differential impacts of resection technique and surgeon’s experience on margin status after robotic PN.

INTRODUCTION AND OBJECTIVE:The final analysis of TITAN confirmed improvement in long-term outcomes in metastatic castration-sensitive prostate cancer (mCSPC) with apalutamide (APA) + androgen depri...

Zusammenfassung Hintergrund Gemäß einer aktuellen Metaanalyse zeigt in Europa jeder zweite Patient mit einem Peniskarzinom (PeK) eine Assoziation mit dem Humanen Papillomavirus (HPV). Es liegen keine Daten darüber vor, inwieweit UrologInnen die Häufigkeit dieser viralen Karzinogenese kennen. Methoden Es wurde ein 14-Items umfassender deutschsprachiger Survey erstellt und in Q3/2018 einmalig an UrologInnen von 45 Kliniken in Deutschland (n = 34), Österreich (n = 8), der Schweiz (n = 2) und Italien/Südtirol (n = 1) verschickt. Insgesamt waren nach vorher definiertem Qualitätsstandard 557 Fragebögen auswertbar (mediane Rücklaufquote 85,7 %). In dem Survey wurde u. a. nach der Häufigkeit HPV-assoziierter PeK in Europa gefragt und 4 Antwortmöglichkeiten vorgegeben: (A)-„ 50 – 75 %“, (D)-„kein Wissen über die Häufigkeit des Zusammenhangs“. Es wurde in der Auswertung eine Toleranz von 50 % akzeptiert, sodass B und C (25 – 75 %) als korrekte Antworten gewertet wurden. Mittels eines Bootstrap-korrigierten multivariaten logistischen Regressionsmodells wurden Kriterien identifiziert, die unabhängig eine richtige Antwort der Befragten vorhersagten. Ergebnisse Die Kategorien A – D wurden von 19,2 % (n = 107), 48,8 % (n = 272), 12,9 % (n = 72) bzw. 19 % (n = 106) als Antwort gewählt, sodass der Endpunkt von 61,8 % (n = 344) der UrologInnen erreicht wurde (B + C). Die selbstständige Durchführung der Chemotherapie durch die Urologische Klinik (OR 1,55; p[Bootstrap] = 0,036) und die Anzahl der urologischen Klinikbetten (OR 1,02; p[Bootstrap] = 0,025) waren die einzigen Studienkriterien, die signifikant das richtige Ergebnis prädizierten. Der Status einer Universitätsklinik (p = 0,143), eine leitende Position der UrologInnen (p = 0,375) bzw. die jährliche Anzahl behandelter PeK-Patienten (p = 0,571) blieben hingegen ohne signifikanten Einfluss auf den Endpunkt. Schlussfolgerung Unsere Studienergebnisse zeigen, dass sich deutschsprachige Klinik-UrologInnen der Häufigkeit einer gegenwärtigen HPV-Assoziation des PeK nur unzureichend bewusst sind.

Context Until recently, there has been a lack of evidence-based treatment alternatives in men with nonmetastatic castrate-resistant prostate cancer (NM-CRPC). However, new evidence-based treatment alternatives are emerging. Objective We aimed to describe time-to-event outcomes in NM-CRPC patients based on evidence from both prospective and retrospective studies. Second, we aimed to describe predictors of these outcomes in the same patient population. Evidence acquisition A systematic review was conducted to identify clinical studies (both prospective and retrospective) in NM-CRPC patients. All published Kaplan-Meier curves were digitized, and individual participant data were extracted using a published and validated R code. The following outcomes were considered: overall survival (OS), bone metastasis-free survival (BMFS), time to bone metastasis (TTBM), metastasis-free survival, time to metastasis, time to progression (TTP), progression-free survival, and time to prostate-specific antigen (PSA) progression. Second, we described all predictor/outcome relationships. Evidence synthesis Median survival times, in months, for OS, BMFS, TTBM, and TTP in placebo arms of randomized clinical trials are 45.3 (95% confidence interval [CI]: 43.5–46.8), 31.5 (95% CI: 28–33.4), 28.8 (95% CI: 25.2–31.6), and 22.2 (95% CI: 19.3–24.8), respectively. In general, reported outcomes in retrospective studies seemed to be longer than those reported in clinical trials. Baseline PSA nadir levels, PSA doubling time, PSA velocity, and alkaline phosphatase velocity are reliable predictors of time-to-event outcomes in NM-CRPC patients, whereas Gleason score is not. Conclusions NM-CRPC is a long-standing condition where effective treatments to slow down disease progression historically have been lacking. Compared with prospective studies, retrospective studies have had limited ability to correctly identify NM-CRPC patients and estimate time to different outcomes in NM-CRPC patients. Patient summary For patients with nonmetastatic castration-resistant prostate cancer (NM-CRPC), currently no effective treatments resulting in longer survival compared with watchful waiting are available. On average, without additional treatment, half of these patients survive

Based on data retrieved from a comprehensive multicenter database, we externally validated a published postoperative nomogram for the prediction of disease-specific survival (DSS) in patients with papillary renal cell carcinoma (papRCC). A multicenter database containing data of 2325 patients with surgically treated papRCC was used as validation cohort. After exclusion of patients with missing data and patients included in the development cohort, 1372 patients were included in the final analysis. DSS-probabilities according to the nomogram were calculated and compared to actual DSS-probabilities. Subsequently, calibration plots and decision curve analyses were applied. The median follow-up was 38 months (IQR 11.8–80.7). Median DSS was not reached. The c-index of the nomogram was 0.71 (95% CI 0.60–0.83). A sensitivity analysis including only patients operated after 1998 delivered a c-index of 0.84 (95% CI 0.77–0.92). Calibration plots showed slight underestimation of nomogram-predicted DSS in probability ranges below 90%: median nomogram-predicted 5-year DSS in the range below 90% was 55% (IQR 20–80), but the median actual 5-year DSS in the same group was 58% (95% CI 52–65). Decision-curve analysis showed a positive net-benefit for probability ranges between a DSS probability of 5% and 85%. The nomogram performance was satisfactory for almost all DSS probabilities; hence it can be recommended for application in clinical routine and for counseling of patients with papRCC.

Purpose Partial nephrectomy (PN) is standard for small renal masses, improving renal function by preserving renal parenchyma compared with radical nephrectomy. Recent work demonstrated that postoperative surgeon assessment of volume preservation (SAVP) and 3D imaging measurements agree and correlate with postoperative function. We hypothesize preoperative assessment of volume preservation (PAVP) with PN based on preoperative imaging will reliably indicate postoperative renal function. Materials and Methods Data were collected from 336 patients undergoing PN for suspected renal cancer by 40 surgeons at 12 centers in Europe and the United States within the Surface-Intermediate-Base International Consortium. Surgeons recorded PAVP and SAVP for individual patients; pre- and postoperative glomerular filtration rate (GFR) was estimated by Chronic Kidney Disease Epidemiology Collaboration equations. Correlations between PAVP, SAVP, and postoperative GFR were assessed with linear regression models. Bland–Altman analysis was used to assess agreement between PAVP and SAVP with a significant cutoff of 5%. Results Median PAVP was 90% (interquartile range [IQR] 85%–100%) and SAVP was 90% (IQR: 80%–94%). PAVP and SAVP were moderately correlated (R2 = 0.67, P Conclusion Renal function is closely linked to the amount of parenchymal volume preservation, whether estimated prior to surgery (PAVP) or afterward (SAVP). PAVP provides reasonably accurate information for decision-making in patients considering PN.

Objective: AI has demonstrated great promise in learning sophisticated features and relations in data that would otherwise remain hidden to the human eye. Here, we developed a proprietary AI-based multimodal approach to integrate clinical, digitized hematoxylin-eosin (H&E), and radiology bone scan (rBS) data for outcome prediction in ADT-treated nmCRPC patients. Identifying prostate cancer patients who may not benefit from ADT could improve the medical management of this disease beyond current definitive therapy. Methods: Patients in the ADT+placebo arm from SPARTAN clinical trial on nmCRPC with available clinical, H&E, and rBS were used (n=154). These patients were randomly divided into 70% (n=107) discovery and 30% (n=47) hold-out test datasets. Using the discovery set, we developed and trained a multimodal approach that combines survival convolutional neural networks (SCNNs1) and Cox proportional-hazards model (CPH) to learn ADT outcomes for overall survival (OS) and time to PSA progression (TTP) from the integration of imaging data and 11 traditional clinical features (e.g., tumor stage, Gleason score, PSA). The ability of the trained framework in predicting outcomes and risk stratification was evaluated on the hold-out set. Bootstrap analysis with Wilcoxon signed rank test was used to determine the significance of the multimodal framework’s performance improvement compared to clinical CPH. Results: The multimodal framework was predictive of ADT outcomes for OS and TTP in nmCRPC patients. In SPARTAN’s hold-out set, the multimodal framework significantly improved the predictive power of clinical CPH by 14%—16% across both outcomes (Wilcoxon signed rank P Conclusion: AI-based framework that learns from the integration of different data types improves outcome prediction in ADT-treated nmCRPC. The multimodal approach demonstrates promise in treatment decision support for the early use of androgen receptor-directed therapy and patient selection for clinical trials with novel treatment combinations. Reference: 1. Mobadersany, Pooya, et al. "Predicting cancer outcomes from histology and genomics using convolutional networks." Proceedings of the National Academy of Sciences 115.13 (2018): E2970-E2979. Conflict of interest statement P.M., J.L., D.G., C.A., S.M., S.B., M.K.Y., K.T., N.H., J.Z., J.G., N.K., and S.S.F.Y., are employees of Janssen Pharmaceutical, LLC. Citation Format: Pooya Mobadersany, Justin Lucas, Darshana Govind, Clemente Aguilar-Bonavides, Sharon McCarthy, Sabine Brookman-May, Margaret K. Yu, Ken Tian, Natalie Hutnick, Jose Zamalloa, Joel Greshock, Najat Khan, Stephen S.F. Yip. Artificial intelligence (AI)-based multimodal framework predicts androgen-deprivation therapy (ADT) outcomes in non-metastatic castration resistant prostate cancer (nmCRPC) from SPARTAN [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5053.

Background: A non-negligible proportion of individuals diagnosed with cT1 renal cell carcinoma (RCC) are upstaged to pT3a at final pathology. Few data on oncological outcomes for these patients are available to determine whether partial nephrectomy (PN) might jeopardise cancer control. Objective: To assess, within an international multi-institutional collaboration, whether PN might undermine cancer control relative to radical nephrectomy (RN) in RCC patients with unexpected pT3a disease. Design, setting, and participants: International multi-institutional collaboration including patients with cT1abN0M0-pT3a RCC. Intervention: PN or RN. Outcome measurements and statistical analysis: We used Kaplan-Meier analyses, before and after propensity-score matching, to evaluate differences in metastatic progression (MP) and cancer-specific mortality (CSM) rates during follow-up. Univariable and multivariable Cox regression analyses were used to assess predictors of MP and CSM. Results and limitations: Overall, 309 patients with cT1abN0M0 RCC (cT1aN0M0, n = 107, 34.6%; cT1bN0M0, n = 202, 65.4%) had pT3a disease according to final pathology. Patients were treated with either PN (n = 71, 23%) or RN (n = 238, 77%). MP at 1, 2, and 5 yr was detected in 9.1%, 13.3%, and 24.1% of patients, respectively. CSM was 3.5%, 10.7%, and 18.4% at 1, 2, and 5 yr, respectively. After matching, no difference in terms of MP or CSM was observed between the PN and RN cohorts (both p>0.3). On multivariable analysis, type of surgery (PN vs RN) was not an independent predictor of either MP (p = 0.3) or CSM (p = 0.4). Limitations include the retrospective design. Conclusions: In patients with unexpected pT3a RCC at final pathology, PN does not appear to jeopardise cancer control with regard to MP and CSM. Patient summary: Cancer control is similar between patients treated with removal of the entire kidney and those with only partial removal, even if the final histology examination demonstrates a tumour that is unexpectedly not confined within the kidney. Partial nephrectomy does not undermine cancer control when unexpected pT3a renal cancer is identified at final pathology.

Although it is well-known that smoking can cause lung cancer, the relationship between smoking and urologic cancers seems not as obvious and awareness is not widespread in the general population. For the KRAUT (knowledge of the relation between smoking and urological tumors among patients with a urological tumor disease) study, 258 patients with the diagnosis of urological cancer were interviewed using a questionnaire. Most (72.1%) stated that they never had a conversation regarding this topic with any doctor. Educational work in this field should be intensified to reduce the development and progression of urologic cancer. Purpose: Our objective was to investigate whether patients with urologic tumors were aware of smoking as a risk factor for the development and progression of several urologic cancers and the extent of the medical education they had received. Another aim was to investigate whether gender or age influenced patients' willingness to change their smoking habits. Materials and Methods: Patients with histologically malignant urologic tumors were enrolled in our questionnaire-based study from September 2013 to December 2014 in 2 urology departments. Patients were asked about their smoking habits and their general understanding of the relationship between smoking and the onset of cancer (urologic cancer and lung cancer). Also, the extent of information they had acquired from a physician was assessed. The descriptive and oncologic data of the patients were recorded. Results: Of 258 enrolled patients, 186 (72.1%) had never had an informational discussion with a doctor about smoking and their urologic tumor disease. Of the 160 active and former smokers, only 45 (28.1%) were planning to stop or reduce smoking because of their tumor disease. The willingness to change smoking habits was greater for women, with a statistically significant difference (odds ratio, 5.59;P = .002). Younger patients aged

Background In SPARTAN, apalutamide improved metastasis-free and overall survival for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) with a prostate-specific antigen doubling time of ≤10 mo. Objective We evaluated health-related quality of life (HRQoL) at the final analysis of the SPARTAN study. Intervention Patients received apalutamide (240 mg/d) or placebo in 28-d cycles. All patients continued androgen deprivation therapy (ADT). Design, setting, and participants A total of 1207 patients with nmCRPC were randomized 2:1 to apalutamide or placebo. Outcome measurements and statistical analysis HRQoL was assessed using Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-3L questionnaires at day 1 of cycle 1 (predose/baseline), cycles 2–6, every two cycles during cycles 7–13, every four cycles thereafter, at the end of treatment, and every 4 mo after progression to 1 yr. Results are presented using descriptive statistics. A mixed model for repeated measures was fitted to estimate the mean scores at each scheduled visit during treatment. Results At final analysis, with 52 mo follow-up for survival, the median treatment duration was 32.9 mo for apalutamide and 11.5 mo for placebo. Patients had good baseline HRQoL. At each scheduled collection during treatment, >90% per group completed the questionnaires. The change in FACT-P total score from baseline to cycles 21 and 25 significantly favored apalutamide over placebo (p = 0.0138 and 0.0009, respectively). The apalutamide group generally maintained favorable FACT-P (total and subscales) and EQ-5D-3L scores, while placebo scores tended to decline over time (starting in cycles 11–13 and pronounced by cycles 21–25). Notably, patient-reported fatigue did not worsen with apalutamide. Most patients reported being “not at all bothered” by side effects, and bother did not increase over time with apalutamide or placebo. Patients receiving apalutamide had minimal change in side-effect bother following symptomatic adverse events. Conclusions Final analysis of SPARTAN confirms that HRQoL is preserved in patients with nmCRPC receiving apalutamide plus ADT, but declines in patients receiving placebo plus ADT after approximately 1 yr. Patient summary Responses from patients with prostate cancer who were included in the SPARTAN study indicated that treatment with apalutamide, even after the most extensive follow-up time possible, did not reduce their quality of life. These results, along with improved survival and longer time to the development of metastases (reported separately), confirm the benefits of apalutamide for patients with nonmetastatic castration-resistant prostate cancer.

IMPORTANCE There is a need to identify prognostic biomarkers to guide treatment intensification in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). OBJECTIVE To examine whether molecular subtypes predict response to apalutamide, using archived primary tumor samples from the randomized, double-blind, phase 3 SPARTAN trial. DESIGN, SETTING, AND PARTICIPANTS In this cohort study, gene expression data from 233 archived samples from patients with nmCRPC enrolled in the SPARTAN trial were generated using a human exon microarray. The present analysis was conducted from May 10, 2018, to October 15, 2020. INTERVENTIONS Patients were randomized (2:1) to apalutamide, 240 mg/d, with androgen deprivation therapy (apalutamide+ADT) or placebo+ADT. MAIN OUTCOMES AND MEASURES Patients were stratified into high-risk and low-risk categories for developing metastases based on genomic classifier (GC) scores for high (GC >0.6) and low to average (GC≤0.6) and into basal and luminal subtypes; associations between these molecular subtypes and metastasis-free survival (MFS), overall survival (OS), and progression-free survival 2 (PFS2) were evaluated using Cox proportional hazards regression and Kaplan-Meier analysis. RESULTS Median age of the 233 included patients was 73 (range, 49-91) years. A total of 116 of 233 patients (50%) in the SPARTAN biomarker subset had high GC scores. Although all patients receiving apalutamide+ADT had improved outcomes, having high GC scores was associated with the greatest improvement in MFS (hazard ratio [HR], 0.21; 95% CI, 0.11-0.40; P

Background The phase 3 SPARTAN study evaluated apalutamide versus placebo in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) and prostate-specific antigen doubling time of ≤10 mo. At primary analysis, apalutamide improved median metastasis-free survival (MFS) by 2 yr and overall survival (OS) data were immature. Objective We report the prespecified event-driven final analysis for OS. Design, setting, and participants A total of 1207 patients with nmCRPC (diagnosed by conventional imaging) were randomised 2:1 to apalutamide (240 mg/d) or placebo, plus on-going androgen deprivation therapy. After MFS was met and the study was unblinded, 76 (19%) patients still receiving placebo crossed over to apalutamide. Outcome measurements and statistical analysis OS and time to cytotoxic chemotherapy (TTChemo) were analysed by group-sequential testing with O’Brien-Fleming-type alpha spending function. Results and limitations At median 52-mo follow-up, 428 deaths had occurred. The median treatment duration was 32.9 mo for apalutamide group and 11.5 mo for placebo group. Median OS was markedly longer with apalutamide versus placebo, reaching prespecified statistical significance (73.9 vs 59.9 mo, hazard ratio [HR]: 0.78 [95% confidence interval {CI}, 0.64–0.96]; p = 0.016). Apalutamide also lengthened TTChemo versus placebo (HR: 0.63 [95% CI, 0.49–0.81]; p = 0.0002). Discontinuation rates in apalutamide and placebo groups due to progressive disease were 43% and 74%, and due to adverse events 15% and 8.4%, respectively. Subsequent life-prolonging therapy was received by 371 (46%) patients in the apalutamide arm and by 338 (84%) patients in the placebo arm including 59 patients who received apalutamide after crossover. Safety was consistent with previous reports; when adverse events were adjusted for treatment exposure, rash had the greatest difference of incidence between the apalutamide and placebo groups. Conclusions Extension of OS with apalutamide compared with placebo conferred impactful benefit in patients with nmCRPC. There was a 22% reduction in the hazard of death in the apalutamide group despite 19% crossover (placebo to apalutamide) and higher rates of subsequent therapy in the placebo group. Patient summary With data presented herein, all primary and secondary study end points of SPARTAN were met; findings demonstrate the value of apalutamide as a treatment option for nonmetastatic castration-resistant prostate cancer.

BACKGROUND: The use of organ sparing strategies to treat penile cancer (PC) is currently supported by evidence that has indicated the safety, efficacy and benefit of this surgery. However, radical penectomy still represents up to 15–20% of primary tumor treatments in PC patients. The aim of the study was to evaluate efficacy in terms of overall survival (OS) and disease-free survival (DFS) of radical penectomy in PC patients. METHODS: Data from a retrospective multicenter study (PEnile Cancer ADherence study, PECAD Study) on PC patients treated at 13 European and American urological centers (Hospital “Sant’Andrea”, Sapienza University, Roma, Italy; “G.D’Annunzio” University, Chieti and ASL 2 Abruzzo, Hospital “S. Pio da Pietrelcina”, Vasto, Italy; Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA; Hospital of Budapest, Hungary; Department of Emergency and Organ Transplantation, Urology and Andrology Unit II, University of Bari, Italy; Hospital “Spedali Civili”, Brescia, Italy; Istituto Europeo di Oncologia, University of Milan, Milan, Italy; University of Modena & Reggio Emilia, Modena, Italy; Hospital Universitario La Paz, Madrid, Spain; Ceara Cancer Institute, Fortaleza, Brazil; Virginia Commonwealth University, Richmond, VA, USA; Aristotle University of Thessaloniki, Thessaloniki, Greece; Maria Skłodowska-Curie Memorial Cancer Center, Warsaw, Poland) between 2010 and 2016 were used. Medical records of patients who specifically underwent radical penectomy were reviewed to identify main clinical and pathological variables. Kaplan-Meier method was used to estimate 1- and 5-year OS and DFS. RESULTS: Of the entire cohort of 425 patients, 72 patients (16.9%) treated with radical penectomy were extracted and were considered for the analysis. The median age was 64.5 (IQR, 57.5–73.2) years. Of all, 41 (56.9%) patients had pT3/pT4 and 31 (43.1%) pT1/pT2. Moreover, 36 (50.0%) were classified as pN1–3 and 5 (6.9%) M1. Furthermore, 61 (84.7%) had a high grade (G2–G3) with 6 (8.3%) positive surgical margins. The 1- and 5-year OS rates were respectively 73.3% and 59.9%, while the 1- and 5-year DFS rates were respectively 67.3% and 35.1%. CONCLUSIONS: PC is an aggressive cancer particularly in more advanced stage. Overall, more than a third of patients do not survive at 5 years and more than 60% report a disease recurrence, despite the use of a radical treatment.

Purpose: The impact of resection technique on partial nephrectomy outcomes is controversial. The aim of this study was to evaluate the pattern of resection techniques during partial nephrectomy and the impact on perioperative outcomes, acute kidney injury, positive surgical margins and the achievement of the Trifecta (negative surgical margins, no perioperative Clavien-Dindo grade 2 or greater surgical complications and no postoperative acute kidney injury). Materials and Methods: We prospectively collected data on consecutive patients with cT1-2N0M0 renal masses treated with partial nephrectomy at a total of 16 referral centers from September 2014 to March 2015. After partial nephrectomy the resection technique was classified by the surgeon as enucleation, enucleoresection or resection according to the SIB (Surface-Intermediate-Base) margin scores 0 to 2, 3 or 4 and 5, respectively. Multivariable logistic regression analysis was done to evaluate the potential impact of the resection technique on postoperative surgical complications, positive surgical margins, acute kidney injury and Trifecta achievement. Results: Overall 507 patients were included in analysis. The resection technique was classified as enucleation in 266 patients (52%), enucleoresection in 150 (30%) and resection in 91 (18%). The resection technique (enucleoresection vs enucleation and resection) was the only significant predictor of positive surgical margins. Tumor complexity, surgical approach (open and laparoscopic vs robotic) and resection technique (enucleoresection vs enucleation) were significant predictors of Clavien-Dindo grade 2 or greater surgical complications. The surgical approach (open and laparoscopic vs robotic), the resection technique (enucleoresection vs enucleation) and warm ischemia time were significantly associated with postoperative acute kidney injury and Trifecta achievement. Conclusions: Resection techniques significantly impact surgical complications, early functional outcomes and positive surgical margins after partial nephrectomy of localized renal masses.

5516 Background: SPARTAN evaluated APA vs PBO in pts with nmCRPC and a prostate-specific antigen doubling time of ≤ 10 mo receiving androgen deprivation therapy (ADT). At primary end point analysis of metastasis-free survival (MFS), APA significantly improved median MFS by 2 yrs, as well as time to metastasis, progression-free survival, and time to symptomatic progression vs PBO (Smith, et al. NEJM 2018); overall survival (OS) results were immature. SPARTAN was unblinded upon meeting the primary end point; pts still on PBO were allowed to cross over to APA. Final survival results are reported herein. Methods: 1207 nmCRPC pts were randomized 2:1 to APA (240 mg QD) or PBO plus ongoing ADT. At progression, pts could receive open-label sponsor-provided abiraterone acetate + prednisone. After the primary efficacy end point (MFS) was met, 76 PBO pts (19%) crossed over to APA. OS and time to cytotoxic chemotherapy (TTCx) were tested by group sequential testing procedure with O’Brien-Fleming (OBF)-type alpha spending function. Time-to-event end points were analyzed by Kaplan-Meier method and Cox model. A sensitivity analysis for OS, accounting for crossover using a naïve censoring approach, was conducted. Results: With follow-up of 52.0 mo, 428 (of 427 required) OS events had occurred. Median treatment duration: APA, 32.9 mo; PBO, 11.5 mo. Median OS was significantly longer with APA + ADT vs PBO + ADT (73.9 vs 59.9 mo), (hazard ratio [HR], 0.784, Table). APA significantly lengthened TTCx (HR, 0.629). Discontinuation rates (APA vs PBO) due to progressive disease were 42.7% vs 73.9%, and due to adverse events (AE) 15.2% vs 8.4%. Safety was consistent with previous reports; grade 3/4 treatment-emergent (TE) AEs of special interest were rash 5.2%, fractures 4.9%, falls 2.7%, ischemic heart disease 2.6%, hypothyroidism 0%, and seizures 0%. 1 TEAE leading to death (myocardial infarction) was considered potentially APA related. Conclusions: In pts with nmCRPC, APA + ADT significantly improved OS compared with PBO + ADT, with median OS > 6 yr in the APA + ADT group and 14 mo improvement over PBO + ADT. Benefit from APA was observed despite a 19% crossover from PBO. The safety profile of APA was consistent with prior interim analyses. Clinical trial information: NCT01946204 . [Table: see text]

Zusammenfassung Hintergrund Bei etwa jedem dritten Patienten mit einem penilen Plattenepithelkarzinom (PSCC) gilt die Infektion mit Humanen Papillomaviren (HPV) als entscheidender Faktor der Karzinogenese. Erste Daten zur optimierten Risikostratifizierung und Therapie anhand des HPV-Status existieren; somit hat der Nachweis einer HPV-Genese möglicherweise mehr als lediglich eine epidemiologische Dimension. Referenz zur Detektion von HPV ist die aufwendige Polymerase-Kettenreaktion (PCR). Unklar ist, ob Alternativen wie die In-situ-Hybridisierung (ISH) oder verschiedene Surrogatmarker (immunhistochemischer Nachweis einer p16INK4a-Expression, histologischer Subtyp, Tumorinvasionsfront, Koilozytose), zur Bestimmung des HPV-Status ausreichend sind. Methoden In dieser unizentrischen Studie an 34 Patienten mit PSCC wurden eine Multiplex nested-PCR zur Festlegung des HPV-Status und Genotypisierung der HPV-DNA sowie eine ISH durchgeführt. Diverse histologische Kriterien und p16INK4a wurden durch zentralen Review bestimmt. Der Einfluss verschiedener Kriterien auf die karzinomspezifische Mortalität (CSM) wurde mit Cox-Regressionsmodellen geprüft (FU: 92 Mon.). Ferner erfolgte der Vergleich der diskriminativen Qualitäten verschiedener Tumorinvasionsmuster (u. a. TNM-Klassifikation 7. vs. 8. Auflage) hinsichtlich der CSM-Prädiktion. Ergebnisse Gemäß PCR-Analyse wiesen 26 % der Patienten HR-HPV auf (n = 9). ISH und die untersuchten histologischen Kriterien zeigten eine unzureichende Vorhersagegenauigkeit des HPV-Status (p > 0,3). p16INK4a erreichte in den Testkriterien Sensitivität, Spezifität, positiv-prädiktiver und negativ-prädiktiver Wert sowie Gesamtübereinstimmung 66,7 %, 84 %, 60 %, 87,5 % bzw. 79,4 % (AUC: 0,753; p = 0,026). Keines der Untersuchungskriterien (inkl. PCR) korrelierte signifikant mit der CSM. Im Vergleich zur 7. wies die 8. Auflage der pT-Klassifikation eine bessere CSM-Prädiktion auf (C-Indizes 70,2 % vs. 72,9 %). In Addition zur Schwellkörper-Invasion besaß die Urethra-Infiltration keinen eigenständigen prädiktiven Wert. Eine durch uns vorgeschlagene Neu-Gruppierung der Schwellkörper-Invasionsmuster erzielte eine Diskriminationssteigerung bzgl. der CSM (C-Index 77,9 %). Schlussfolgerung p16INK4a erlaubt – im Gegensatz zur ISH und den untersuchten histologischen Kriterien – eine akzeptable Vorhersage des HPV-Status. Der Nachweis von HPV-DNA inkl. seiner Surrogatmarker hatte keinen Einfluss auf die CSM. Die 8. Auflage der pT-Klassifikation scheint prognostisch sinnvoll, da die urethrale Tumorinvasion keinen eigenständigen Einfluss auf die CSM aufweist.

ZusammenfassungEinige Prinzipien der primären Therapie des Peniskarzinoms haben sich in den letzten Jahrzehnten grundlegend verändert: Galt aufgrund der Aggressivität des Tumors bei der Penisteilamputation vor 15 Jahren noch ein tumorfreier Sicherheitsabstand von 2 cm als obligat, so gilt heute, dass weitgehender Organerhalt Priorität hat und minimale tumorfreie Schnittränder ausreichend sind. Es besteht somit der Grundsatz: So viel Organerhalt wie möglich, so viel Radikalität wie nötig. Auch hat sich zunehmend die Erkenntnis durchgesetzt, dass Patienten mit begrenzter regionär-lymphogener Metastasierung heilbar sein können, allerdings nur bei Durchführung einer multimodalen Therapie bestehend aus einer radikalen inguinalen Lymphadenektomie und nachfolgenden adjuvanten Chemotherapie. Bei Patienten mit fixierten inguinalen Lymphknotenmetastasen konnte hingegen die neoadjuvante Chemotherapie etabliert werden. Trotz der verbesserten Therapieoptionen bleiben die funktionellen und onkologischen Ergebnisse bei der Behandlung des Peniskarzinoms vielfach enttäuschend. Die Möglichkeiten des Organerhalts mittels rekonstruktiver operativer Techniken verbessern zwar die Lebensqualität der Langzeitüberlebenden erheblich, doch weniger als 25 % der Patienten mit Lymphknotenmetastasierung überleben ihre Tumorerkrankung. Von großer Bedeutung ist die chirurgische Lymphknotendiagnostik bei klinisch unauffälligen Lymphknoten ab dem Tumorstadium T1b, da hier eine okkulte Mikrometastasierung in bis zu 25 % der Fälle vorliegen kann. Die minimal-invasive Sentinel-Lymphknoten-Biopsie ist ein durchaus sinnvoller Weg, diese Patienten zu diagnostizieren, ohne gleich die Morbidität einer primär radikalen Lymphadenektomie hervorzurufen. Ein zunehmendes Verständnis der zugrundeliegenden Tumorbiologie, insbesondere Erkenntnisse zum Humanen-Papillomavirus- und Epidermal-Growth-Factor-Receptor-Status, brachten zuletzt erfolgversprechende klinische Studien auf den Weg; zudem wird gegenwärtig die gezielte Immuntherapie mittels Immun-Checkpoint-Inhibitoren bei therapierefraktärem Peniskarzinom geprüft.In diesem Review werden die aktuellen Aspekte des therapeutischen Managements von Peniskarzinom-Patienten zusammengefasst.

Background: TITAN, a phase 3 placebo (PBO)-controlled study in a broad population of pts with mCSPC (NCT02489318), demonstrated that the addition of APA to androgen deprivation therapy (ADT) significantly improved radiographic progression-free survival (rPFS) (median rPFS in the APA and PBO groups was not reached and was 22.1 months, respectively) and overall survival (OS) compared with PBO + ADT (Chi N Engl J Med 2019). This exploratory analysis investigated molecular signatures of pts with mCSPC who had long-term responses to APA. Methods: Pts (n = 222) in the biomarker cohort of TITAN were characterized as long-term responders (LTR) or early progressors (EP) by separating rPFS into quartiles. The last quartile with longest rPFS (APA, n = 28; PBO, n = 28) represented LTR. The first quartile, with shortest rPFS (APA, n = 17; PBO, n = 21) represented EP. Gene expression profiles of TITAN pts were generated from archival primary prostate tumors; data were summarized based on 110 predefined gene signatures. Mean signature scores between LTR and EP groups were compared within treatment groups using 2 sample t tests to evaluate whether effects were prognostic or specific to APA treatment. Signatures were also evaluated for association with outcome using Cox proportional hazard models in each treatment group. Results: At primary analysis, with median 22.7 months follow-up, median rPFS was, respectively, not reached and 32.9 months in APA and PBO pts in the LTR group, and 10.9 and 3.7 months in APA and PBO pts in the EP group. A higher level of expression (above median) of either polycomb repressor complex 2 activation or the Decipher signature was more frequently associated with EP in both groups. LTR in the APA treatment group, but not those in the PBO group, had lower expression of transcriptional signatures describing myeloid-derived suppressor cells (MDSCs) and cell cycle progression. These results suggest that pts with mCSPC who have relatively lower levels of MDSCs in the tumor, indicative of a less immune-suppressed tumor microenvironment, may have long-term benefit from treatment with APA. Conclusions: Consistent clinical benefit was observed with the addition of APA to ADT in both EP and LTR. Although the data require confirmation in larger studies, these molecular signatures may have utility in selecting pts with mCSPC who may derive the most benefit from APA and other androgen signaling inhibitors. Citation Format: Justin Lucas, Neeraj Agarwal, Felix Feng, Clemente Aguilar-Bonavides, Shibu Thomas, Michael Gormley, Suneel Mundle, Sabine Brookman-May, Sharon A. McCarthy, Anders Bjartell, Hirotsugu Uemura, Simon Chowdhury, Kim N. Chi. Molecular signatures associated with long-term response to apalutamide (APA) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in TITAN [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 359.

To analyze the impact of gender on the clinicopathologic features and survival of patients with surgically treated papillary renal cell carcinoma (papRCC) using a comprehensive international multicenter database.Data of 2325 patients undergoing surgery for unilateral papRCC between 1984 and 2015 in 17 European and North American centers were retrospectively collated. The impact of clinicopathologic features on the likelihood of nephron-sparing surgery (NSS) was evaluated using a multivariable logistic regression model. The influence on cancer-specific mortality (CSM) and other-cause mortality was analyzed by multivariable competing-risk regression models. Finally, subgroup analyses were conducted for organ-confined (n = 2075) and non-organ-confined tumors (n = 250). The median follow-up was 47 months.The study cohort included 1782 (77%) male patients (male-to-female ratio 3.3:1.0). Considering age, symptoms at presentation, performance status, pathologic tumor size, stage, and grade, we observed that there were no significant gender-specific differences. In contrast, female patients underwent NSS significantly less frequently (P .001). On multivariable analysis, the likelihood of NSS was 72% higher in male patients after adjusting for all relevant cofactors (P .001). No significant gender-specific differences in terms of CSM and other-cause mortality were demonstrated, but CSM was 59% lower in female patients in the subgroup of organ-confined tumors (P = .001).No impact of gender on survival was found analyzing this large cohort of patients undergoing surgery for papRCC. However, CSM appears to be lower in female patients with organ-confined disease. In this context, it is interesting that the likelihood of NSS seems to be significantly higher in male patients.

Zusammenfassung Hintergrund Es liegen derzeit keine Untersuchungen darüber vor, welchen Kenntnisstand Chirurgen im Vergleich mit Nichtchirurgen über multiresistente Erreger (MRE) und den rationalen Einsatz von Antibiotika haben (Antibiotic Stewardship/ABS). Methode Im Rahmen der MR2-Studie (Multiinstitutional Reconnaissance of practice with MultiResistant bacteria – a survey focussing on German hospitals) wurde ein Fragebogen mit 4 + 35 Punkten in 18 deutschen Krankenhäusern an Urologen, Internisten, Gynäkologen und Chirurgen verteilt. Mit multivariaten logistischen Regressionsmodellen wurde der Einfluss der Fachrichtung auf verschiedene prädeterminierte Endpunkte geprüft. Ergebnisse Es konnten 456 auswertbare Fragebögen analysiert werden, wobei sich die Rücklaufquote bei Chirurgen (156/330, 47%) und Nichtchirurgen (300/731, 41%) nur insignifikant unterschied (p = 0,061). Chirurgen gaben in der Selbsteinschätzung im Vergleich mit Nichtchirurgen eine signifikant geringere Sicherheit bei der korrekten Wahl von Dosierung, Frequenz und Dauer der Antibiotikagabe (p = 0,005), der Entscheidung einer intravenösen vs. oralen Antibiotikaverordnung (p = 0,005) sowie der korrekten Interpretation der mikrobiologischen Befunde (p = 0,023) an. Sowohl Chirurgen als auch Nichtchirurgen schätzten ihr Wissen zu ABS als gering ein. Die Kenntnis der lokalen E.-coli-Resistenz gegen Ciprofloxacin unterschied sich zwischen Chirurgen und Nichtchirurgen nur insignifikant (27,6 vs. 35,3% waren in der richtigen Kategorie; p = 0,114), wobei 64% der Chirurgen diese lokalen Resistenzen unterschätzten. Beide Gruppen sahen in dem häufigen Einsatz von Breitspektrumantibiotika ein wesentliches Problem, das für die Zunahme von MRE verantwortlich ist. Andererseits wurde das gewählte Fallbeispiel einer stark symptomatischen Patientin mit unkomplizierter Harnwegsinfektion von beiden Gruppen ähnlich häufig mit einem Breitspektrumantibiotikum behandelt (34,0 vs. 29,3%; p = 0,331). Gemäß der multivariaten Modelle besuchten Chirurgen im Vergleich zu Nichtchirurgen in den letzten 12 Monaten nicht häufiger eine Weiterbildungsveranstaltung zum Thema der MRE/ABS und gaben auch keine bessere Qualität ihrer Klinikepikrisen hinsichtlich der exakten Auflistung von MRE an. Schlussfolgerungen Es sollten in den Kliniken obligat ABS-Programme implementiert werden, die u. a. eine regelmäßige Fortbildung der Kollegen unabhängig von ihrer Fachrichtungen vorsehen.

A recent meta-analysis showed that penile cancer (PeC) is associated with the human papilloma virus (HPV) in 50 % of patients in Europe. It is unknown whether urologists are aware of the impact of viral carcinogenesis.A (German-language) survey comprising 14 items was created and sent to urologists of 45 clinical centres in Germany (n = 34), Austria (n = 8), Switzerland (n = 2) and Italy/South Tyrol (n = 1) once in Q3/2018. According to a predefined quality standard, a total of 557 surveys were eligible for final data analysis (response rate: 85.7 %). Among other questions, urologists were asked to state the frequency of HPV-associated PeC in Europe. 4 potential answers were provided: (A)-" 25 %", (B)-"25 - 50 %", (C)-" 50 - 75 %", (D)-"level of association unknown". For the final calculation, a tolerance of ± 50 % was considered acceptable, so B and C were deemed correct answers. Based on a bootstrap-adjusted multivariate logistic regression model, criteria independently predicting a correct answer were identified.Categories A-D were selected in 19.2 % (n = 107), 48.8 % (n = 272), 12.9 % (n = 72) and 19 % (n = 106), respectively, representing a rate of 61.8 % of urologists (n = 344) reaching the endpoint (B + C). Autonomous performance of chemotherapy for PeC by urologists within the given centre (OR 1.55, p[Bootstrap] = 0.036) and the centre's number of urological beds (OR 1.02, p[Bootstrap] = 0.025) were the only parameters showing a significant independent impact on the endpoint. In contrast, the status of a university centre (p = 0.143), a leading position of the responding urologist (p = 0.375) and the number of PeC patients treated per year and centre (p = 0.571) did not significantly predict a correct answer.Our results demonstrate insufficient knowledge on the association of PeC and HPV among German-speaking urologists.Gemäß einer aktuellen Metaanalyse zeigt in Europa jeder zweite Patient mit einem Peniskarzinom (PeK) eine Assoziation mit dem Humanen Papillomavirus (HPV). Es liegen keine Daten darüber vor, inwieweit UrologInnen die Häufigkeit dieser viralen Karzinogenese kennen.Es wurde ein 14-Items umfassender deutschsprachiger Survey erstellt und in Q3/2018 einmalig an UrologInnen von 45 Kliniken in Deutschland (n = 34), Österreich (n = 8), der Schweiz (n = 2) und Italien/Südtirol (n = 1) verschickt. Insgesamt waren nach vorher definiertem Qualitätsstandard 557 Fragebögen auswertbar (mediane Rücklaufquote 85,7 %). In dem Survey wurde u. a. nach der Häufigkeit HPV-assoziierter PeK in Europa gefragt und 4 Antwortmöglichkeiten vorgegeben: (A)-„ 25 %“, (B)-„25 – 50 %“, (C)-„ 50 – 75 %“, (D)-„kein Wissen über die Häufigkeit des Zusammenhangs“. Es wurde in der Auswertung eine Toleranz von 50 % akzeptiert, sodass B und C (25 – 75 %) als korrekte Antworten gewertet wurden. Mittels eines Bootstrap-korrigierten multivariaten logistischen Regressionsmodells wurden Kriterien identifiziert, die unabhängig eine richtige Antwort der Befragten vorhersagten.Die Kategorien A – D wurden von 19,2 % (n = 107), 48,8 % (n = 272), 12,9 % (n = 72) bzw. 19 % (n = 106) als Antwort gewählt, sodass der Endpunkt von 61,8 % (n = 344) der UrologInnen erreicht wurde (B + C). Die selbstständige Durchführung der Chemotherapie durch die Urologische Klinik (OR 1,55; p[Bootstrap] = 0,036) und die Anzahl der urologischen Klinikbetten (OR 1,02; p[Bootstrap] = 0,025) waren die einzigen Studienkriterien, die signifikant das richtige Ergebnis prädizierten. Der Status einer Universitätsklinik (p = 0,143), eine leitende Position der UrologInnen (p = 0,375) bzw. die jährliche Anzahl behandelter PeK-Patienten (p = 0,571) blieben hingegen ohne signifikanten Einfluss auf den Endpunkt.Unsere Studienergebnisse zeigen, dass sich deutschsprachige Klinik-UrologInnen der Häufigkeit einer gegenwärtigen HPV-Assoziation des PeK nur unzureichend bewusst sind.

To validate the adherence of urologists to chemotherapy recommendations given in the EAU guidelines on PeCa. The European Association of Urology (EAU) guidelines on penile cancer (PeCa) are predominantly based on retrospective studies with low level of evidence. A 14-item-survey addressing general issues of PeCa treatment was developed and sent to 45 European hospitals. 557 urologists participated in the survey of which 43.5%, 19.3%, and 37.2% were in-training, certified, and in leading positions, respectively. Median response rate among participating departments was 85.7% (IQR 75–94%). Three of 14 questions addressed clinical decisions on neoadjuvant, adjuvant, and palliative chemotherapy. Survey results were analyzed by bootstrap-adjusted multivariate logistic-regression-analysis to identify predictors for chemotherapy recommendations consistent with the guidelines. Neoadjuvant, adjuvant, and palliative chemotherapy was recommended according to EAU guidelines in 21%, 26%, and 48%, respectively. For neoadjuvant chemotherapy, urologists holding leading positions or performing chemotherapy were more likely to recommend guideline-consistent treatment (OR 1.85 and 1.92 with p(bootstrap) = 0.007 and 0.003, respectively). Supporting resources (i.e., guidelines, textbooks) were used by 23% of survey participants and significantly improved consistency between treatment recommendations and Guideline recommendations in all chemotherapy settings (p(bootstrap) = 0.010–0.001). Department size and university center status were no significant predictors for all three endpoints. In this study, we found a very low rate of adherence to the EAU guidelines on systemic treatment for PeCa. Further investigations are needed to clarify whether this missing adherence is a consequence of limited individual knowledge level or of the low grade of guideline recommendations.

BACKGROUND: One major objective of currently available morphometric scores (MS) for renal masses, i.e., R.E.N.A.L., PADUA classification, Centrality-Index, is the prediction of type of surgery (nephron-sparin surgery [NSS] or radical nephrectomy [RN]). METHODS: Based on a prospective study protocol, various MS were assigned and calculated for 108 patients undergoing surgical treatment for renal masses at a single academic center. MS calculation was based on preoperative computed-tomography or magnet-resonance-imaging and performed by two independent readers blinded for surgical approach and outcome. Multivariable logistic-regression- and ROC-analyses were performed to assess the predictive value of various MS for surgical approach and the correlation of clinical parameters with nephrectomy type. Furthermore, the association with perioperative outcome parameters was evaluated. RESULTS: None of the tested MS was significantly superior to tumor size alone (area under the curve [AUC]=0.82) in predicting RN, with Centrality-Index showing the best association (AUC-0.88). Based on these findings, a simplified and optimized R.E.N.A.L. Score (optR.E.N.A.L.) was developed with different weightings of included parameters, which did not only show a significantly enhanced association with surgery type (AUC=0.93) than tumor size, but also outperformed all 1st and 2nd generation MS tested in the study cohort. Besides a modest correlation with postoperative change in renal function, no association with perioperative outcome variables was found for all MS including optR.E.N.A.L.. CONCLUSIONS: optR.E.N.A.L. represents a promising improvement of the preexisting R.E.N.A.L. Score with higher predictive ability for nephrectomy type than established MS and may serve as a benchmarking tool for nephrectomy assessment and comparison of surgical strategies.

Contains fulltext : 215812.pdf (Publisher’s version ) (Closed access) CONTEXT: To date, established risk factors for prostate cancer (PCa) are limited to age, race, family history, and certain genetic polymorphisms. Despite great research efforts, available evidence on potentially modifiable risk factors is conflicting. Moreover, most studies on PCa risk factors did not consider the impact of prostate-specific antigen (PSA) testing on PCa diagnosis. OBJECTIVE: To provide a detailed overview of the latest evidence on the role of metabolic diseases, drugs, and dietary factors for risk of PCa incidence, recurrence, and survival in men exposed to PSA testing. EVIDENCE ACQUISITION: A systematic review of the English-language literature was performed using the MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses recommendations. Randomized, case-control, or cohort studies published during the periods 2008-2017 (on drugs and metabolic diseases) and 2003-2017 (on dietary factors), with extensive follow-up (>/=8-10yr for studies on PCa risk; >/=2-5yr for studies on PCa recurrence, progression, and survival, depending on the review subtopic) and adjusting of the analyses, beyond established risk factors, for either rate of PSA testing (for risk analyses) or PCa stage and primary treatment (for survival analyses), were eligible for inclusion. EVIDENCE SYNTHESIS: Overall, 39 reports from 22 observational studies were included. Studies were heterogeneous regarding definitions of exposure or outcomes, length of follow-up, risk of bias, and confounding. For some risk factors, evidence was insufficient to assess potential effects, while for others there was no evidence of an effect. For selected risk factors, namely metformin, aspirin and statin use, diabetes, obesity, and specific dietary intakes, there was low-quality evidence of modest effects on PCa risk. CONCLUSIONS: Current evidence from long-term observational studies evaluating the effect of drugs, metabolic diseases, and dietary factors for PCa risk considering the impact of PSA testing is still not conclusive. Future research is needed to confirm the associations suggested by our review, exploring their potential biological explanations and selecting those risk factors most likely to trigger effective public health interventions. PATIENT SUMMARY: We reviewed the available studies published in the recent literature on the potential role of drugs, metabolic diseases, and food and dietary factors for the risk of prostate cancer, considering the impact of prostate-specific antigen testing on prostate cancer diagnosis. We found that for some factors data are currently insufficient to make definitive conclusions, while for others available studies seem to indicate an effect on the risk of prostate cancer.

Contains fulltext : 215820.pdf (Publisher’s version ) (Closed access) CONTEXT: Smoking, sexual activity, and physical activity (PA) are discussed as modifiable lifestyle factors associated with prostate cancer (PCa) development and progression. OBJECTIVE: To evaluate the available evidence concerning the association of smoking, sexual activity, and sports and exercise on PCa risk, treatment outcome, progression, and cancer-specific mortality. EVIDENCE ACQUISITION: A systematic review of studies published between 2007 and 2017 using MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement criteria was conducted. EVIDENCE SYNTHESIS: While data concerning the impact of smoking on PCa development remain conflicting, there is robust evidence that smoking is associated with aggressive tumor features and worse cancer-related outcome, which seems to be maintained for 10 yr after smoking cessation. Less convincing and limited evidence exists for the association of sexual activity with PCa risk. The findings related to PA and PCa support the inference that exercise might be a useful factor in the prevention of PCa and tumor progression, while it is not finally proved under which specific conditions PA might be protective against disease development. CONCLUSIONS: Smoking is associated with aggressive tumor features and worse cancer-related prognosis; as this negative impact seems to be maintained for 10yr after smoking cessation, urologists should advise men to quit smoking latest at PCa diagnosis to improve their prognosis. As several studies indicate a positive impact of exercise on tumor development, progression, and treatment outcome, it is certainly reasonable to advocate an active lifestyle. Least convincing evidence is available for the interaction of sexual activity and PCa, and well-conducted and longitudinal studies are clearly necessary to evaluate whether the suggested associations between PCa risk and sexual behavior are real or spurious. PATIENT SUMMARY: In this systematic review, we looked at the impact of smoking, sexual activity, and sports and exercise on prostate cancer risk and outcome after treatment. While the evidence for sexual activity is not overall clear, we found that smoking might lead to more aggressive cancers and result in worse treatment outcome. Physical activity might prevent prostate cancer and improve cancer-related outcomes as well. Hence, it is certainly reasonable to advocate an active lifestyle and advise men to quit smoking.

Background To externally validate‚ BioScore’, a biomarker-based scoring system using immunohistochemical tumor expression levels of B7-H1, survivin, and Ki-67, in a single-center cohort of renal cell carcinoma (RCC) patients. Additionally, we investigated the potential benefit of BioScore as compared to the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score. Materials and Methods The validation cohort comprised 393 nonmetastatic RCC patients treated with radical nephrectomy or nephron-sparing surgery from 1999 to 2004. Kaplan-Meier estimators, the log-rank test, uni- and multivariable Cox regression models, and measures of discrimination were used to quantify the prognostic performance of BioScore regarding cancer-specific mortality (CSM). Results During a median follow-up of 7.8 years, 69/132 (52%) deaths were adjudicated to progressive disease. BioScore was weakly associated with CSM in univariable analysis (hazard ratio per 1 point increase = 1.12, 95% confidence interval = 1.02–1.23, P = 0.023). However, this association did not prevail after adjusting for other adverse prognostic factors as represented by the SSIGN score. The discriminative performance of BioScore was very modest (Harrell's C-Index = 0.60) and did not improve the SSIGN score (P = 0.341), which already showed an excellent discrimination, as evidenced by Harrell's C-Index of 0.81. In a sensitivity analysis regarding clear cell RCC patients only, B7-H1 positivity did not emerge as a statistically significant predictor of CSM. Conclusion Although a higher BioScore was significantly associated with a higher CSM, the magnitude of this association was weak and not independent from other prognosticators. Moreover, BioScore did not improve the prognostic accuracy of the SSIGN score.

5037 Background: In the double-blind PBO-controlled ACIS study, investigator-assessed radiographic progression-free survival (rPFS) was significantly improved with APA + AAP vs PBO + AAP in chemo-naive mCRPC, with no significant new safety signals (Rathkopf ASCO GU 2021). Among prespecified subgroups, efficacy and safety were explored in two difficult to treat subgroups: pts with visceral disease (VD; liver, lung, and/or adrenal gland metastasis) or age ≥ 75 y. Methods: Pts with mCRPC with ongoing ADT and no prior life-prolonging treatment were randomized 1:1 to APA (240 mg QD) + AA (1000 mg QD) + P (5 mg BID) or PBO + AAP. Stratified: presence or absence of VD, ECOG PS 0 or 1, geographic region. Primary end point: rPFS (randomization to radiographic progression or death); secondary end points: overall survival (OS), time to initiation of cytotoxic chemotherapy, time to chronic opioid use, time to pain progression, safety. Results: 982 pts enrolled. 14.6% had VD and 35.9% were ≥ 75 y. Median rPFS, OS, and time to pain progression favored APA + AAP vs AAP (HR < 1) in both subgroups (Table). For pts ≥ 75 y, rPFS and OS were ≥ 7 mo longer with APA + AAP. Overall, treatment-emergent adverse events (TEAEs) were similar (all > 94%) in pts with VD, ≥ 75 y, and overall safety population; hypertension was more frequent with APA + AAP vs AAP mainly in pts ≥ 75 y (31.7% vs 17.6%). Grade 3/4 TEAEs (APA + AAP vs AAP): VD, 60.8%, n = 74 vs 48.5%, n = 68; ≥ 75 y, 71.5%, n = 186 vs 68.5%, n = 165; overall, 63.3%, n = 490 vs 56.2%, n = 489. TEAEs leading to discontinuation: VD, 17.6% vs 5.9%; ≥ 75 y, 26.3% vs 20.6%; overall, 16.9% vs 12.5%. TEAEs leading to death: VD, 6.8% vs 5.9%; ≥ 75 y, 5.4% vs 13.9%; overall, 3.5% vs 7.6%. Conclusions: In this analysis of two difficult to treat subgroups, addition of APA to AAP favored rPFS and OS. Safety, while generally consistent with the overall population, showed higher hypertension rate in ≥ 75 y and TEAEs leading to discontinuation in VD. Clinical trial information: NCT02257736. [Table: see text]

5068 Background: The phase 3 TITAN study evaluated APA vs PBO in pts with mCSPC receiving ADT. At primary analysis with 22.7 mo median follow-up, APA significantly improved overall survival (OS) and radiographic progression-free survival vs PBO (Chi NEJM 2019) while preserving HRQoL (Agarwal Lancet Oncol 2019). The study was unblinded; pts on PBO were allowed to cross over to APA. At final analysis with 44 mo median follow-up, APA significantly improved OS vs PBO, reducing risk of death by 35% despite crossover (Chi ASCO GU 2021). We evaluated HRQoL and treatment bother at final analysis. Methods: mCSPC pts (N = 1052) were randomized 1:1 to APA (240 mg QD; n = 525) or PBO (n = 527). All pts received ADT. Patient-reported outcomes were assessed using Brief Pain Inventory-Short Form (BPI-SF) and Functional Assessment of Cancer Therapy-Prostate (FACT-P). BPI was completed for 7d consecutively (Days -6 to 1 of each 28-d cycle [C]) through end of treatment (EOT). FACT-P was completed at baseline (BL), C2-C7, then every other C through EOT. Mean scores were reported by treatment group and over time. Time to deterioration on BPI and FACT-P scores was calculated by Kaplan-Meier methods and compared between groups by fitting proportional hazards regression models. Results: Of eligible pts per C, > 62% completed BPI through C32 and > 50% completed FACT-P through C31. Pts were relatively asymptomatic with good BL HRQoL: on 0-10 worst pain severity scale (BPI), median scores were 1.1 (APA) and 1.0 (PBO); on 0-156 HRQoL scale (FACT-P total; higher score = better HRQoL), median scores were 113.0 (APA) and 113.3 (PBO). Low BL BPI scores remained stable over time in both groups. On average, favorable BL FACT-P scores did not notably worsen over time in APA or PBO groups. There were no significant differences between groups in median time to deterioration in any BPI or FACT-P scores (Table). At each C at least 86% (APA) and 85% (PBO) of pts were either “not at all” or “a little bit” bothered by side effects. At BL, 76% (APA) and 72% (PBO) had favorable energy levels (reporting lack of energy “not at all” or “a little bit”). Energy levels remained stable or improved at each C for > 78% (APA) and > 71% (PBO) of pts. Conclusions: In the final analysis of TITAN, survival benefit with addition of APA to ADT was achieved without significant patient-reported side effect burden or reduced HRQoL compared with PBO in pts with mCSPC. Clinical trial information: NCT02489318. [Table: see text]