Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with next-generation androgen receptor inhibitors. However, direct comparative data are not available to inform treatment decisions and/or guideline recommendations. Therefore, we performed network meta-analysis to indirectly compare the efficacy and safety of currently available treatments. Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or metastasis-free and/or prostate-specific antigen (PSA) progression-free survival (OS/MFS/PSA-PFS) and/or adverse events (AEs) in nmCRPC patients were considered eligible. Three studies (n = 4117) met our eligibility criteria. Formal network meta-analyses were conducted. For MFS, apalutamide, darolutamide, and enzalutamide were significantly more effective than placebo, and apalutamide emerged as the best option (P score: 0.8809). Apalutamide [hazard ratio (HR): 0.85, 95% credible interval (CrI): 0.77–0.94] and enzalutamide (HR: 0.86, 95% CrI: 0.78–0.95) were both significantly more effective than darolutamide. For PSA-PFS, all three agents were statistically superior to placebo, and apalutamide emerged as the likely preferred option (P score: 1.000). Apalutamide (HR: 0.71, 95% CrI: 0.69–0.74) and enzalutamide (HR: 0.76, 95% CrI: 0.74–0.79) were both significantly more effective than darolutamide. For AEs (including all AEs, grade 3 or grade 4 AEs, grade 5 AEs, and discontinuation rates), darolutamide was the likely best option. Apalutamide and enzalutamide appear to be more efficacious agents for therapy of nmCRPC, while darolutamide appears to have the most favorable tolerability profile. These findings may facilitate individualized treatment strategies and inform future direct comparative trials.

Objectives: To present an overall picture of the evidence regarding the association of erectile dysfunction (ED) with cardiovascular disease (CVD). Methods: Systematic reviews and meta‐analyses that studied the association of ED with any CVD were included in this umbrella review. We did not restrict the population to a particular group or age. PubMed, Embase, the Joanna Briggs Institute (JBI) Database of Systematic Reviews and Implementation Reports, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, and the PROSPERO register were searched to find relevant systematic reviews, with or without meta‐analyses, from inception to April 2020. The JBI Checklist for Systematic Reviews and Research Syntheses was used for the critical appraisal. Only studies with acceptable quality were included. Two independent reviewers extracted the data using the JBI data extraction tool for qualitative and quantitative data extraction. Results: The summary estimate showed a higher risk of CVD (relative risk [RR] 1.45, 95% confidence interval [CI] 1.36–1.54; P < 0.001), coronary heart disease (RR 1.50, 95% CI 1.37–1.64; P < 0.001), cardiovascular‐related mortality (RR 1.50, 95% CI 1.37–1.64; P < 0.001), all‐cause mortality (RR 1.25, 95% CI 1.18–1.32; P < 0.001), myocardial infarction (RR 1.55, 95% CI 1.33–1.80; P < 0.001) and stroke (RR 1.36, 95% CI 1.26–1.46; P < 0.001) in patients with ED than in other patients. Conclusions: Our results confirm that ED is an independent predictor of CVD and their outcomes. ED and CVD are two presentations of the same physiological phenomenon. ED normally precedes symptomatic CVD, providing a window of opportunity for healthcare practitioners to screen and detect high‐risk patients early to prevent avoidable morbidity and mortality.

Objectives: To perform a systematic review and network meta‐analysis to compare the efficacy and safety of currently available treatments for the management of metastatic hormone‐sensitive prostate cancer (mHSPC), as there has been a paradigm shift with the use of next‐generation androgen receptor inhibitors (ARIs) and docetaxel. Methods: Multiple databases were searched for articles published before May 2020 according to the Preferred Reporting Items for Systematic Review and Meta‐analysis extension statement for network meta‐analysis. Studies comparing overall/progression‐free survival (OS/PFS) and/or adverse events (AEs) in patients with mHSPC were eligible. Results: Nine studies ( N = 9960) were selected, and formal network meta‐analyses were conducted. Abiraterone (hazard ratio [HR] 0.83, 95% credible interval [CrI] 0.76–0.90), docetaxel (HR 0.90, 95% CrI 0.82–0.98), and enzalutamide (HR 0.85, 95% CrI 0.73–0.99) were associated with significantly better OS than androgen‐deprivation therapy (ADT), and abiraterone emerged as the best option. Abiraterone (HR 0.71, 95% CrI 0.67–0.76), apalutamide (HR 0.73, 95% CrI 0.65–0.81), docetaxel (HR 0.84, 95% CrI 0.78–0.90), and enzalutamide (HR 0.67, 95% CrI 0.63–0.71) were associated with significantly better PFS than ADT, and enzalutamide emerged as the best option. Abiraterone (HR 0.85, 95% CrI 0.78–0.93), apalutamide (HR 0.87, 95% CrI 0.77–0.98), and enzalutamide (HR 0.80, 95% CrI 0.73–0.88) were significantly more effective than docetaxel. Regarding AEs, apalutamide was the likely best option among the three ARIs. In patients with low‐volume mHSPC, enzalutamide was the best option in terms of OS and PFS. Conclusions: All three ARIs are effective therapies for mHSPC; apalutamide was the best tolerated. All three seemed more effective than docetaxel. These findings may facilitate individualised treatment strategies and inform future comparative trials.

This study aimed to evaluate the concordance in tumor stage and grade between ureteroscopic (URS) biopsy and radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). Records of 1,214 UTUC patients who had undergone URS biopsy followed by RNU were included. Univariable and multivariable logistic regression analyses were performed to identify factors contributing to the pathological upstaging. The concordance between URS biopsy-based clinical and RNU pathological staging was 34.5%. Clinical understaging occurred in 59.5% patients. Upstaging to muscle-invasive disease occurred in 240 (41.7%) of 575 patients diagnosed with ≤cT1 disease. Of those diagnosed with muscle-invasive disease on final pathology, 89.6% had been clinically diagnosed with ≤cT1 disease. In the univariable analyses, computed tomography urography (CTU)-based invasion, ureter location, hydronephrosis, high-grade cytology, high-grade biopsy, sessile architecture, age, and women sex were significantly associated with pathological upstaging (P < .05). In the multivariable analyses, CTU-based invasion and hydronephrosis remained associated with pathological upstaging (P < .05). URS biopsy-based clinical and pathological gradings were concordant in 634 (54.2%) patients. Clinical undergrading occurred in 496 (42.4%) patients. Clinical understaging/undergrading and upstaging to muscle-invasive disease occurred in a high proportion of UTUC patients undergoing RNU. Despite the inherent selection bias, these data underline the challenges of accurate UTUC staging and grading. In daily clinical practice, URS biopsy and CTU offer the most accurate preoperative information albeit with limited predictive value when used alone. These findings should be considered when utilizing preoperative, risk-adapted strategies.

Purpose: Management of metastatic renal cell cancer (mRCC) has undergone a paradigm shift with immune-checkpoint inhibitors (ICI) in the first-line setting. However, direct comparative data are inadequate to inform treatment decisions. Therefore, we aimed to assess first-line therapy for mRCC and indirectly compare the efficacy and safety of currently available treatments. Materials and methods: Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or progression-free survival (OS/PFS) and/or adverse events (AEs) in mRCC patients were considered eligible. Results: Six studies matched our eligibility criteria. For OS, pembrolizumab plus axitinib [hazard ratio (HR) 0.85, 95% credible interval (CrI) 0.73–0.98] and nivolumab plus ipilimumab (HR 0.86, 95% CrI 0.75–0.99) were significantly more effective than sunitinib, and pembrolizumab plus axitinib was probably the best option based on analysis of the treatment ranking. For PFS, pembrolizumab plus axitinib (HR 0.86, 95% CrI 0.76–0.97) and avelumab plus axitinib (HR 0.85, 95% CrI 0.74–0.98) were statistically superior to sunitinib, and avelumab plus axitinib was likely to be the preferred option based on analysis of the treatment ranking, closely followed by pembrolizumab plus axitinib. Nivolumab plus ipilimumab had significantly lower rates of serious AEs than sunitinib. Conclusion: Pembrolizumab plus axitinib seemed to be the most efficacious first-line agents, while nivolumab plus ipilimumab had the most favorable efficacy–tolerability equilibrium. These findings may facilitate individualized treatment strategies and inform future direct comparative trials in an expanding treatment options without direct comparison between approved drugs.

Purpose: To assess the prognostic value of alkaline phosphatase in patients with hormone-sensitive prostate cancer. Methods: A systematic review and meta-analysis was performed using the PUBMED, Web of Science, Cochrane Library, and Scopus in April 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared hormone-sensitive prostate cancer patients with high vs. low alkaline phosphatase to determine its predictive value for overall survival, cancer-specific survival, and progression-free survival. We performed a formal meta-analysis of these outcomes. Results: 42 articles with 7938 patients were included in the systematic review and 28 studies with 5849 patients for the qualitative assessment. High alkaline phosphatase was associated with worse overall survival (pooled HR 1.72; 95% CI 1.37−2.14) and progression-free survival (pooled HR 1.30; 95% CI 1.10−1.54). In subgroup analyses of patients with “high-volume” and “low-volume”, alkaline phosphatase was associated with the overall survival (pooled HR 1.41; 95% CI 1.21−1.64 and pooled HR 1.64; 95% CI, 1.06−2.52, respectively). Conclusions: In this meta-analysis, elevated serum levels of alkaline phosphatase were associated with an increased risk of overall mortality and disease progression in patients with hormone-sensitive prostate cancer. In contrast, those were not associated with an increased risk of cancer-specific mortality. Alkaline phosphatase was independently associated with overall survival in both patients with “high-volume” and “low-volume” hormone-sensitive prostate cancer. Alkaline phosphatase may be useful for being integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision making process.