Real-World Burden and Management of Late Genitourinary Toxicity After Prostate Radiotherapy: Insights from IRRADIaTE, the Italian Registry of Radiotherapy-Associated Disorders and Urological Treatment & Evaluation

Background and objective: Radiotherapy (RT) is a key curative option for localized prostate cancer (PC). However, data on late genitourinary toxicity, especially adverse events requiring urgent care or hospitalization, remain limited. The aim of the Italian Registry of Radiotherapy-Associated Disorders and Urological Treatment & Evaluation (IRRADIaTE) is to characterize the burden and management of severe genitourinary adverse events following prostate RT across multiple high-volume centers in Italy. Methods: A prospective, observational, multicenter registry was established in 2024 across 20 Italian institutions. Men with localized PC previously treated with curative, adjuvant, or salvage RT who presented with late (≥6 mo) genitourinary complications requiring urgent medical attention were enrolled. Demographics, treatment details, and outcomes were collected. Toxicity grading followed Common Terminology Criteria for Adverse Events. Primary endpoints were prespecified as (1) the cumulative incidence of grade 3-5 events with death as a competing risk and (2) hospitalization-free survival from RT completion. Analyses were descriptive and adjusted for prespecified confounders only. Key findings and limitations Among 321 patients, 50% received primary RT, and 50% postprostatectomy RT. At the time of admission, 43% presented with grade 3-5 genitourinary toxicity. Over 5 yr, the hospitalization-free survival rate declined from 86% to 42%. Higher cumulative incidence of severe events was observed in the primary RT group. The percentage of patients who did not require major surgery to manage RT-related complications decreased from 81% (95% confidence interval [CI] 76-97%) at 12 mo after RT to 66% (95% CI 48-79%) at 60 mo. Differences in baseline age and comorbidity profiles between the RT treatment settings must be acknowledged. Because the registry enrolls only men presenting with complications, population-level incidence and causal effects cannot be inferred. Conclusions and clinical implications: Late genitourinary toxicity after prostate RT is substantial and often resource-intensive. Differences observed by treatment setting are associational; attribution of causal mechanisms and treatment effects requires dedicated causal-inference studies.