Late Urinary Toxicity and Quality of Life With Pelvic Radiation Therapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase 3 Trial

The POP-RT phase 3 randomized trial showed improved biochemical failure-free survival and metastasis-free survival with whole pelvic radiation therapy versus prostate-only radiation therapy for high and very high-risk prostate cancer, albeit with worse RTOG late urinary toxicity. We report updated late urinary adverse effects and bladder dose-effect relations within this trial. Late urinary toxicity and the cumulative severity of each symptom during the follow-up period were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Bladder dosimetry in 5-Gy increments (V5, V10, V15, V65, V68Gy) in the approved radiation therapy plans was compared with urinary symptoms and overall grade 2+ toxicity. Potential factors influencing urinary toxicity were tested using multivariable logistic regression analysis. Updated urinary quality of life (QOL) scores were compared between the trial arms. Complete combined data for late urinary symptoms and dosimetry was available for 193 of 224 patients. At a median follow-up of 75 months, cumulative late urinary CTCAE grade 3 toxicity was low and similar for whole pelvic radiation therapy and prostate-only radiation therapy (5.2% vs 4.1%, P = .49), and grade 2 toxicity was 31.3% versus 22.7%, respectively (P = .12). Cumulative rates of each urinary symptom were similar between both arms. Multivariable analysis with age at diagnosis, known diabetes, tumor stage, trial arm, prior transurethral resection of prostate, grade 2+ acute urinary toxicity, low bladder dose (V10Gy), and moderate bladder dose (V40Gy) did not identify any significant association with late urinary toxicity. Urinary QOL scores was similar between both the arms for all the symptoms. During long-term follow-up, whole pelvic radiation therapy resulted in low (∼5%) and similar grade 3 cumulative urinary toxicity as prostate-only radiation therapy. The long-term patient-reported QOL scores were similar. No causative factors affecting the late urinary toxicity were identified.