Late urinary toxicity and QOL with pelvic radiotherapy for high-risk prostate cancer: Dose-effect relations in the POP-RT randomized phase III trial

The POP-RT phase III randomized trial showed improved biochemical failure-free survival and metastasis-free survival with whole pelvic radiotherapy (WPRT) versus prostate-only radiotherapy (PORT) for high/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 cumulative severity of each symptom over the follow-up period was graded using CTCAE v5.0. Bladder dosimetry in 5-Gy increments (V5, V10, V15...V65Gy, V68Gy) in the approved radiotherapy plans was compared for 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 193/224 patients. At a median follow-up of 75 months, cumulative late urinary CTCAE grade 3 toxicity was low and similar for WPRT and PORT (5.2% vs 4.1%, p=0.49), while grade 2 toxicity was 31.3% vs 22.7% respectively (p=0.12). Cumulative rates of each urinary symptom were similar between both arms. Multivariable analysis with age at diagnosis, known diabetes, tumor stage, trial arm, prior TURP, 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.Over long term follow up, whole pelvic radiotherapy resulted in low (∼5%) and similar grade 3 cumulative urinary toxicity as prostate-only radiotherapy. The long term patient-reported QOL scores were similar. No causative factors affecting the late urinary toxicity were identified.