Prognostic significance of pretreatment hydronephrosis in radiotherapy-based bladder-preserving strategies for muscle-invasive bladder cancer: a systematic review and meta-analysis

INTRODUCTION & OBJECTIVES: Radiotherapybased bladder-preserving strategies are established alternatives to radical cystectomy for selected patients with muscle-invasive bladder cancer (MIBC), yet survival outcomes remain heterogeneous and prognostic stratification is imprecise. Pretreatment hydronephrosis has shown adverse prognostic associations in cystectomy and trimodality therapy cohorts, but its impact across the broader spectrum of radiotherapy-based bladder preservation is unclear. This systematic review and meta-analysis aimed to quantify the prognostic significance of pretreatment hydronephrosis on survival outcomes in MIBC patients treated with radiotherapy-based bladder-preserving strategies. MATERIALS & METHODS: The study was designed as a systematic review with quantitative synthesis, structured around a predefined PICO framework. The protocol was prospectively registered in PROSPERO (CRD420261305703). Eligible studies included observational cohorts and clinical trials enrolling adults with MIBC treated with definitive radiotherapy-based bladder preservation, including radiotherapy alone, concurrent chemoradiotherapy, or trimodality therapy. Searches of PubMed, ScienceDirect, the Cochrane Library, Google Scholar, and Wiley Online Library were performed from January 2000 to December 2025. Risk of bias was assessed with ROBINS-I and study quality with Newcastle-Ottawa Scale. Time-to-event outcomes were extracted as hazard ratios (HRs) with 95% confidence intervals (CIs), prioritizing multivariable-adjusted estimates. Evidence synthesis was performed using random-effects models with inverse-variance weighting of log-transformed HRs according to the DerSimonian-Laird method. RESULTS: Forty-two studies comprising 8,586 participants met the inclusion criteria. Pretreatment hydronephrosis was significantly associated with inferior overall survival (HR 1.65, 95% CI 1.43- 1.91; I² 29.8%). This adverse effect was consistent across treatment modalities, including definitive chemoradiotherapy (HR 1.74, 95% CI 1.30-2.32; I² 34%), radiotherapy alone (HR 1.65, 95% CI 0.38-7.19; I² 0%), and trimodality therapy (HR 1.64, 95% CI 1.25-2.14; I² 39.6%), with no evidence of subgroup interaction (p = 0.93). Hydronephrosis was also associated with worse cancer-specific survival (HR 2.00, 95% CI 1.68-2.37; I² 8.9%). Disease control endpoints were consistently inferior in patients with hydronephrosis, including disease-free survival (HR 1.83, 95% CI 1.12-3.01; I² 48.7%), progression-free survival (HR 1.59, 95% CI 1.02-2.49; I² 0%), and metastasis-free survival (HR 1.56, 95% CI 1.32-1.84; I² 0%). The overall risk of bias across included studies was predominantly moderate. CONCLUSIONS: Pretreatment hydronephrosis is a robust, treatmentindependent adverse prognostic factor in radiotherapy-based bladder-preserving management of muscle-invasive bladder cancer, conferring consistently increased hazards for mortality and disease progression across all major oncologic endpoints. Its presence should be systematically integrated into baseline prognostic stratification, patient counseling, and risk-adapted surveillance strategies in bladder-preserving treatment paradigms.