David D’ Andrea

Objectives: To investigate the rate and predictors of recurrence at second-look ureterorenoscopy (URS) and to assess the adequate timeframe for second-look URS in upper tract urothelial carcinoma (UTUC). Methods: This multicenter retrospective study included 179 patients who underwent endoscopic kidney-sparing surgery (KSS) and second-look URS for non-invasive UTUC between 2004 and 2017. We performed logistic and Cox proportional hazard regression analyses to investigate the association between clinical parameters and second-look recurrence, recurrence-free survival (RFS), and cancer-specific mortality. The optimal duration to second-look URS was extrapolated using restricted cubic splines. Results: Overall, 66 (36.9%) patients experienced recurrence at second-look URS. After second-look URS, further recurrence was observed in 87 (48.6%) patients during a median follow-up of 12 months. Female gender (OR [odds ratio] 2.3, 95% CI [confidence interval] 1.1–4.7, p = 0.026) and tumor size > 1 cm (OR 3.3, 95% CI 1.2–9.5, p = 0.027) were independently associated with recurrence at second look. Second-look recurrence was a strong prognostic factor for RFS (HR 5.0, 95% CI 3.1–8.0, p < 0.001). Second-look URS between 5 and 12 weeks after initial endoscopic laser ablation was an independent favorable factor for RFS (HR 0.5, 95% CI 0.3–0.9, p = 0.014). Conclusions: Early recurrence at second-look URS appears to be one of the strongest predictive factors for RFS in patients undergoing endoscopic KSS. Our results suggest that second-look URS performed within 5 to 12 weeks is associated with a lower probability of further disease recurrence. Given that this interval was derived and tested in the same cohort, this finding should be regarded as hypothesis-generating and requires external validation before being adopted as a clinical standard.

Standard management for recurrent low-grade non-muscle-invasive bladder cancer (LG-NMIBC) often involves a substantial treatment burden, which is not justified by the relatively indolent course of the disease, prompting a need for de-intensification strategies. Active surveillance (AS) is an alternative approach aimed at reducing overtreatment in selected patients. However, the broader adoption of AS is hindered by a lack of standardized protocols for patient selection, monitoring and intervention. To address this gap, we conducted an international, two-round Delphi consensus among 51 bladder cancer experts to establish foundational statements for the use of AS. Consensus was achieved on 20 statements, providing clear recommendations for terminology; inclusion and exclusion criteria; follow-up monitoring; and exit criteria. This Delphi consensus provides the first expert-driven framework to standardize the clinical application of AS for LG-NMIBC. These statements could guide current clinical practice and unify the design of future trials.

Background Incidental prostate cancer (IPC) is not uncommon in patients undergoing surgery for benign prostate enlargement (BPE). However, the associated risk factors remain incompletely understood. This study aimed to evaluate potential clinical predictors of IPC. Methods A systematic search of MEDLINE, Embase, and Web of Science was conducted in January 2025 to identify studies assessing risk factors for IPC. Pairwise meta-analyses were performed using a random-effects model, pooling adjusted odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable analyses. Risk of bias was evaluated using the ROBINS-I tool. (PROSPERO: CRD42024588776). Results Twenty-five studies comprising 247,966 patients were included. IPC was identified in 6,748 patients, with reported rates ranging from 2.2% to 49.6%. Significant risk factors for IPC included: Elevated PSA level (OR: 1.03; 95% CI: 1.01–1.05; p = 0.01), PSA density >0.15 ng/mL/cc (OR: 3.02; 95% CI: 1.50–6.07; p = 0.01), Older age (OR: 1.05; 95% CI: 1.01–1.08; p = 0.01), and Higher body mass index (BMI) (OR: 1.10; 95% CI: 1.02–1.18; p = 0.01). Prostate volume, diabetes, and dyslipidemia were not associated with IPC risk. Notably, use of 5-alpha reductase inhibitors (5-ARIs) was linked to a significantly reduced risk (OR: 0.53; 95% CI: 0.33–0.85; p = 0.01). Study limitations included heterogeneity across studies, retrospective designs, and incomplete reporting of key variables. Conclusions Elevated PSA, high PSA density, older age, and increased BMI were associated with a higher risk of IPC in patients undergoing surgery for BPE. Conversely, preoperative use of 5-ARIs was associated with a reduced risk. These findings may support improved preoperative risk stratification and help identify patients in whom additional diagnostic evaluations could be considered or avoided. Further research is needed to better define predictors of clinically significant IPC.

Objective: To develop a data‐driven risk‐stratification model to identify high‐risk patients following radical cystectomy (RC) for bladder cancer and propose a risk‐adapted follow‐up (FU) schedule. Patients and Methods: We performed a retrospective analysis of an individual patient data registry comprising 3196 patients with clinical T stage (cT)2–T4 N0M0 bladder cancer who underwent RC at 16 European centres (1990–2024). All treatment decisions, including the use of neoadjuvant chemotherapy, adjuvant therapy, and the FU schedule, were made at the discretion of the treating physician in accordance with the patient's preference. A Classification and Regression Tree (CART) analysis, incorporating pathological T and N stages, lymphovascular invasion (LVI), and other features, was used to stratify patients into Low‐Risk and High‐Risk groups for recurrence. The primary endpoint was recurrence‐free survival (RFS). We used a landmark analysis to evaluate the conditional risk of recurrence at 1, 2, 3, 4, and 5 years after RC. Results: At a median FU of 81.8 months, 891 patients recurred. CART analysis identified a High‐Risk group (pathological T stage [pT]3–pT4, node‐positive disease, or pT2 with LVI) with significantly worse 5‐year RFS than the Low‐Risk group (37.8% vs 76.2%; P < 0.001). This stratification was strongly prognostic for recurrence (hazard ratio [HR] 4.29; 95% confidence interval 3.63–5.00), cancer‐specific survival (subdistribution HR 5.80), and overall survival (HR 3.04) (all P < 0.001). Landmark analysis confirmed that the elevated risk persisted up to 4 years; however, the conditional risk for event‐free patients converged after 5 years (HR 1.37; P = 0.3). Conclusions: This study establishes a simple, pathologically derived model (pT3–4/pN+/pT2 + LVI) that effectively stratifies post‐RC patients, enabling a risk‐adapted FU strategy. Prospective evaluation of this framework is required to confirm its clinical utility, safety, and cost‐effectiveness.

Objective: To evaluate the prognostic impact of T‐stage at re‐transurethral resection of bladder (TURB) and its utility for refining risk stratification across European Association of Urology 2021 (EAU21) risk groups in patients with T1 high‐grade (HG) non‐muscle‐invasive bladder cancer (NMIBC) treated with adequate Bacillus Calmette–Guérin (BCG). Patients and Methods: Retrospective multicentre study including patients with primary or secondary T1HG NMIBC treated with TURB, re‐TURB, and adequate BCG between 2007 and 2020 across 28 European academic centres. Patients were stratified according to re‐TURB pathological stage (T0, Ta, Tis, T1) and EAU21 risk groups. Kaplan–Meier, Cox regression, and competing‐risk methods were used to evaluate recurrence‐free survival (RFS), HG‐RFS, progression‐free survival (PFS), and cancer‐specific mortality (CSM). A mixture cure model estimated statistical cure fractions for the overall cohort. Results: Among 1403 patients, residual disease at re‐TURB was identified in 38.8%, including 17.7% with persistent T1. Residual T1 was consistently associated with worse outcomes. Compared with T0/Ta, persistent T1 at re‐TURB showed substantially lower 5‐year HG‐RFS and PFS, with high‐grade recurrence in over half of patients and 5‐year progression up to 48% in high‐ and very high‐risk groups. The 5‐year CSM rose from 6–7% (T0/Ta) to 23% (T1). On multivariable analysis, residual T1 was independently associated with worse HG‐RFS (hazard ratio 2.40), PFS (hazard ratio 3.10), and CSM (hazard ratio 3.00). Cure modelling showed lower cure fractions for residual T1 compared with T0/Ta. Conclusion: Residual T1 at re‐TURB is strongly associated with adverse long‐term oncological outcomes in BCG‐treated T1HG NMIBC and markedly reduces the likelihood of statistical cure. High‐ and very high‐risk patients with persistent T1 represent a biologically adverse subgroup in whom standard BCG may be insufficient.

Objective: To examine the impact of specific Bacillus Calmette–Guérin (BCG) failure phenotypes on treatment outcomes with intravesical gemcitabine/docetaxel in high‐risk non‐muscle‐invasive bladder cancer (HR‐NMIBC). Patients and Methods: A BCG failure was classified according to the United States Food and Drug Administration (FDA)/International Bladder Cancer Group (IBCG) definitions and analysed as early refractory BCG failure, early non‐refractory BCG failure, or late BCG relapse. Kaplan–Meier methods were used to estimate recurrence‐free survival (RFS), high‐grade RFS (HG‐RFS), and progression‐free survival (PFS). Multivariable Cox proportional hazards models, adjusted for histology, multifocality, and tumour size, were used to assess the association between BCG failure patterns and oncological outcomes. Results: Among the 143 patients included, 72 had early non‐refractory BCG failure, 36 had early refractory BCG failure, and 35 experienced late BCG relapse. The median follow‐up was 12 months. At 12 months, the RFS was 67% (95% confidence interval [CI] 55–82%) in early non‐refractory BCG failure, 54% (95% CI 36–82%) in early refractory BCG failure, and 84% (95% CI 70–100%) in late BCG relapse ( P < 0.05). Corresponding HG‐RFS rates were 75% (95% CI 64–88%), 58% (95% CI 39–87%), and 87% (95% CI 75–100%), respectively ( P < 0.05). The PFS remained >90% across all groups at 12 months. On multivariable analysis, both early non‐refractory BCG failure (adjusted hazard ratio [aHR] 3.20, 95% CI 1.31–7.82; P = 0.011) and early refractory BCG failure (aHR 3.59, 95% CI 1.28–10.1; P = 0.015) were associated with a significantly higher risk of recurrence compared with late BCG relapse, with consistent findings for HG recurrence. Conclusions: Gemcitabine/docetaxel demonstrated meaningful activity across all BCG failure types, with late BCG relapsing patients achieving the most favourable outcomes and refractory disease showing the poorest control. These findings underscore the clinical relevance of distinguishing BCG failure subtypes when selecting candidates for post‐BCG intravesical gemcitabine/docetaxel and designing future prospective trials.

Purpose: To evaluate novel intravesical and systemic combination therapies for improving outcomes in BCG-naïve patients with non-muscle invasive bladder cancer (NMIBC), this systematic review and meta-analysis assessed first-line treatment strategies, including combinations with systemic immune-checkpoint inhibitors (ICIs). Methods: In this prospectively registered review (CRD420251163026), MEDLINE, Embase, Web of Science, and the ESMO 2025 abstract book were searched for randomized controlled trials (RCTs) evaluating first-line therapies in BCG-naïve NMIBC. Meta-analyses estimated HRs for recurrence-related time-to-event outcomes (disease-free and event-free survival). Grade ≥ 3 treatment-related adverse events were pooled as relative risks (RRs). Risk of bias was assessed using the Cochrane RoB 2 tool. Results: Out of 5202 records screened, six RCTs including 3485 patients were eligible. Modifications to intravesical BCG alone (three trials, n = 895) did not significantly improve recurrence-related outcomes. Systemic ICIs given additional to intravesical BCG significantly reduced recurrence-related events compared to BCG alone (HR 0.77, 95%CI 0.6–0.97, n = 1899; number needed to treat at two years: 25), but increased grade ≥ 3 treatment-related adverse events by a statistically and clinically significant margin (RR 3.97, 95% CI 2.53–6.22, n = 1879; number needed to treat to harm one patient: 5). Sensitivity analysis using the ALBAN alternative endpoint of high-grade recurrence-free survival yielded HR 0.78 (95% CI 0.59–1.02), not reaching statistical significance. Limitations included heterogeneity in trial design and endpoint definitions. Conclusion: In BCG-naïve NMIBC, systemic ICIs combined with intravesical BCG improve recurrence-related outcomes but are offset by a substantially increased risk of severe treatment-related adverse events. These findings highlight the need for careful, risk-based, biomarker-guided patient selection to balance over- and undertreatment within a shared decision-making process.