
Prostate Radiotherapy May Be Linked to Late GU Toxicities
The differences in treatment setting are associational and are likely influenced by confounding by indication and not treatment effects.
Late genitourinary (GU) toxicity following prostate radiotherapy was observed among men with localized prostate cancer treated with curative, adjuvant, or salvage radiotherapy, according to findings from the prospective, observational Italian Registry of Radiotherapy-Associated Disorders and Urological Treatment & Evaluation (IRRADIaTE) published in European Urology Oncology.
Specifically, among 325 patients with suspected late GU complications the median time from radiotherapy to urgent consultation for a treatment-related complication was 24 months (IQR, 9-58). A total of 27%, 30%, and 47% experienced grade 1, 2, or 3 or higher adverse effects (AEs) per CTCAE at admission. Moreover, of those patients, 131 required hospitalization.
Hospitalization-free survival was 86% (95% CI, 79%-91%) at 12 months vs 42% (95% CI, 33%-50%) at 60 months, after a median follow-up of 15 months (IQR, 5-29) for event-free patients. Moreover, a higher subdistribution HRs for severe events were observed with primary radiotherapy vs patients who had received it postoperatively (P < .001). Additionally, age at diagnosis was significantly linked to presence of severe AEs.
The rate of patients who did not require major surgery for management of radiotherapy-related complications decreased from 81% (95% CI, 76%-97%) at 12 months to 66% (95% CI, 48%-79%) at 60 months. Furthermore, the distribution of management strategies differed across treatment settings, with more conservative and endoscopic management employed in the radiotherapy only group, and nonsurgical or major surgery options employed more frequently in the adjuvant or salvage groups (P = .05).
“Late [GU] toxicity after prostate [radiotherapy] is common among men who present for urgent care and frequently requires invasive management. Differences observed by treatment setting are associational and are probably influenced by confounding by indication; these differences should not be interpreted as treatment effects,” lead author Riccardo Bertolo, MD, PhD, assistant professor of Urology at the University of Verona in Verona, Italy, wrote in the publications with study coinvestigators. “Causal effects of treatment pathways should be evaluated using denominator-based, prospectively specified causal-inference designs.”
The study period occurred from January 1 to December 31, 2024, with no restrictions on the date of prior radiotherapy. Institutions were selected on a voluntary basis within the AGILE urological collaborative group, and all were referral centers with urology and radiotherapy departments. Men who underwent radiotherapy for treatment of localized prostate cancer and who experienced at least 1 GU complication attributable to radiotherapy occurring more than 6 months after treatment were screened for enrollment.
In the primary (n = 160), adjuvant (n = 105), and salvage radiotherapy groups (n = 56), the median age at diagnosis was 76 years (IQR, 71-79), 66 years (IQR, 61-70), and 65 years (IQR, 60-69). Among each of the respective groups, the median Charlston Comorbidity Index (CCI) was 6 (IQR, 4-7), 3 (IQR, 2-5), and 3 (IQR, 2-5), and 84%, 74%, and 70% of each group had hypertension. Most patients in each group were nonsmokers (44%, 45%, 50%), had clinical stage 2 tumors (40%, 65%, 58%), and were biopsy grade 4 (47%, 36%, 36%) or 3 (21%, 30%, 38%) at diagnosis.
Across all cohorts, the median radiotherapy dose was 68 Gy (IQR, 60-72), with treatment lasting longer than 5 weeks in 55% of patients.
The study prospectively collected demographic and medical history variables, and patients were followed for the entire extent of evaluation and management of sequela per standard clinical practice. Radiotherapy-related complications were recorded in free text and were classified per CTCAE schema.
Reference
Bertolo R, Pastore AL, Verze P, 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. Published online January 24, 2026. doi:10.1016/j.euo.2026.01.005
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