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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.

We aimed to evaluate the correlation between endoscopic papillary abnormalities (PA) and high renal papilla Hounsfield density (PHD) on CT scan in patients who underwent flexible ureteroscopic treatment (fURS) for renal stones. We retrospectively assessed patients from a prospectively collected database who were treated with fURS for renal stones between May 2016 and October 2020. PHD was measured on preoperative CT-scan by a radiologist blinded from the intraoperative aspect of the papillae. Correlation was examined between high PHD (≥ 43 HU) and PA described in fURS, stone composition, metabolic abnormalities, … Out of 159 consecutive cases, 131 were eligible for analysis with available preoperative CT-scan. Median age was 55 years (IQR 43–67) and median PHD was 40 (IQR 36–45). Eighty patients (61%) had PHD < 43, and 51 patients (39%) had PHD ≥ 43. In univariate and multivariate analysis, only young age (p-value = 0.017) and insufficient diuresis (p-value = 0.008) were correlated with high PHD. No significant correlation was found with PA described during endoscopy, including the intensity of Randall's plaques. In this study, high PHD appears to be only a sign of insufficient diuresis, with no significant correlation with potential PA.

PurposeManagement 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 methodsMultiple 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.ResultsSix 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.ConclusionPembrolizumab 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.

ObjectiveWe conducted a systematic review and meta-analysis to assess the available literature regarding the surgical and oncologic outcomes of patients undergoing salvage radical cystectomy (SV-RC) for recurrence or failure of bladder sparing therapy (BST) for muscle-invasive bladder cancer (MIBC).MethodsWe searched MEDLINE (PubMed), EMBASE and Google Scholar databases in May 2020. We included all studies of patients with ≥ cT2N0/xM0 bladder cancer that were eligible for all treatment modalities at the time of treatment decision who underwent BST including radiotherapy (RTX). A meta-analysis was conducted to calculate the pooled rate of several variables associated with an increased need for SV-RC. Study quality and risk of bias were assessed using MINORS criteria.Results73 studies comprising 9110 patients were eligible for the meta-analysis. Weighted mean follow-up time was 61.1 months (range 12–144). The pooled rate of non-response to BST and local recurrence after BST, the two primary reasons for SV-RC, was 15.5% and 28.7%, respectively. The pooled rate of SV-RC was 19.2% for studies with a follow-up longer than 5 years. Only three studies provided a thorough report of complication rates after SV-RC. The overall complication rate ranged between 67 and 72% with a 30-day mortality rate of 0–8.8%. The pooled rates of 5 and 10-year disease-free survival after SV-RC were 54.3% and 45.6%, respectively.ConclusionApproximately one-fifth of patients treated with BST with a curative intent eventually require SV-RC. This procedure carries a proportionally high rate of complications and is usually accompanied by an incontinent urinary diversion.

The objectives of this study are to evaluate the available literature regarding the oncologic effect of neoadjuvant and adjuvant chemotherapy in the treatment of patients with clinically non-metastatic upper tract urothelial carcinoma (UTUC) and locally advanced UTUC. We searched PubMed, Cochrane Library, and Scopus databases in November 2019, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We included studies that compared patients with non-metastatic UTUC who received either neoadjuvant or adjuvant chemotherapy with patients who underwent surgery alone. Subgroup meta-analyses were also performed for studies that investigated only locally advanced UTUC. Overall, 36 studies were included in the review of which 22 studies and 15,378 patients were eligible for the meta-analysis. Neoadjuvant chemotherapy (NAC) was associated with higher rates of pathological downstaging (pDS) (RR 6.48, 95% CI 2.05–20.44, p = 0.001) and pathological complete response (RR 18.46, 95% CI 3.34–99.24, p = 0.001); and this was also proven in a subgroup analysis of studies that evaluated pDS in locally advanced UTUC (RR 3.18, 95% CI 2.0–5.07, p < 0.001). The association of NAC with overall survival (OS) and cancer-specific survival (CSS) was also statistically significant in all patients and in patients with locally advanced UTUC. Adjuvant chemotherapy (AC) was associated with improved metastasis-free survival (HR 0.65, 95% CI 0.55–0.76, p < 0.001) and CSS (HR 0.66, 95% CI 0.57–0.77, p < 0.001), which continued to be true for the patients with locally advanced UTUC. The association of AC with OS was only significant in patients with locally advanced UTUC. Perioperative chemotherapy might provide better survival outcomes in patients with clinically non-metastatic UTUC treated with radical nephroureterectomy. Neoadjuvant chemotherapy seems to have promising results, although high level of evidence is still lacking. Despite the low level, the body of evidence suggests a need for multimodal therapy of invasive UTUC.

BackgroundTriplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear.MethodsWe performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist.ResultsOverall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64–0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52–0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease.ConclusionsTriplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT.

Pembrolizumab is the standard for the first and second lines in treating metastatic urothelial carcinoma (UC). This systematic review and meta-analysis aimed to assess the value of pretreatment clinical characteristics and hematologic biomarkers for prognosticating response to pembrolizumab in patients with metastatic UC. PUBMED®, Web of Science™, and Scopus® databases were searched for articles published before May 2021 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they evaluated overall survival (OS) in patients with metastatic urothelial carcinoma treated with pembrolizumab and pretreatment clinical characteristics or laboratory examination. Overall, 13 studies comprising 1311 patients were eligible for the meta-analysis. Several pretreatment patients’ demographics and hematologic biomarkers were significantly associated with worse OS as follows: Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥ 2 (Pooled hazard ratio [HR]: 3.24, 95% confidence interval [CI] 2.57–4.09), presence of visceral metastasis (Pooled HR: 1.84, 95% CI 1.42–2.38), presence of liver metastasis (Pooled HR: 4.23, 95% CI 2.18–8.20), higher neutrophil–lymphocyte ratio (NLR) (Pooled HR: 1.29, 95% CI 1.07–1.55) and, higher c-reactive protein (CRP) (Pooled HR: 2.49, 95% CI 1.52–4.07). Metastatic UC patients with poor PS, liver metastasis, higher pretreatment NLR and/or CRP have a worse survival despite pembrolizumab treatment. These findings might help to guide the prognostic tools for clinical decision-making; however, they should be interpreted carefully, owing to limitations regarding the retrospective nature of primary data.

Bladder cancer outcomes differ between men and women. Elucidating this sexual dimorphism, genomic analyses found differing molecular subtype distributions and androgen response activities in muscle-invasive bladder cancer in men and women. Together with knowledge of cancer driver genes, biomarkers and clinical characteristics, these findings will hopefully lead to sex-based personalized research and management of bladder cancer.

BackgroundThis systematic review and meta-analysis aimed to assess the prognostic value of sequential of abiraterone (ABI) and enzalutamide (ENZ) therapy in patients with castration-resistant prostate cancer (CRPC).MethodsPUBMED, Web of Science, Cochrane Library, and Scopus databases were searched for articles published prior to December 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared overall survival (OS), combined progression-free survival (PFS), combined prostate specific antigen (PSA)-PFS, and PSA response rates in CRPC patients receiving sequential ABI/ENZ or vice versa. PSA response to both the first and second agents was defined as a >50% decrease in PSA achieved with each of these agents. Formal meta-analyses were performed for these outcomes.ResultsTen studies with 1096 patients were eligible for the systematic review and eight studies with 643 patients for the meta-analysis. The ABI-to-ENZ sequence was significantly associated with better PFS (pooled hazard ratio (HR): 0.62, 95% confidential interval (CI): 0.49–0.78, P < 0.001), and PSA–PFS (pooled HR: 0.48, 95% CI: 0.38–0.61, P < 0.001) than the ENZ-to-ABI sequence. PSA response rates of both agents were significantly better with the ABI-to-ENZ sequence (risk ratio: 0.21, 95% CI: 0.09–0.47, P < 0.001). In contrast, treatment sequence was not significantly associated with OS (pooled HR: 0.77, 95% CI: 0.59–1.01, P = 0.055).ConclusionsABI-to-ENZ sequential therapy in patients with CRPC was associated with better PFS, PSA–PFS, and PSA response rates. Regardless of sequencing, response to drug therapy was transient for both ABI and ENZ when either agent was used as a secondary therapy. Despite this, treatment sequencing is important to achieve the maximum possible benefit from available drugs in CRPC.