Reply to Shilpa Gupta, Maria Carmen Mir, and Daniel E. Spratt’s Letter to the Editor re: Riccardo Bertolo, Antonio Luigi Pastore, Paolo Verze, et al. 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. Eur Urol Oncol. In press. http://dx.doi.org/10.1016/j.euo.2026.01.005

Second, the study design is not ''selection-on-the-outcome'' in the causal-inference sense, but is inherently descriptive.IRRADIaTE enrolls patients presenting with complications.Cox and competing-risk models are used to describe clinical trajectories and management burden, with prespecified confounder adjustment; they are not intended to infer treatment-related risks.No causal claims are made 1,3.The concern regarding immortal-time bias is not applicable: time zero is clearly defined (radiotherapy RT completion), and stratifications are not based on future events.