Late Urinary Toxicity and QoL with Curative Radiotherapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase III Trial

Abstract

Whole pelvic radiotherapy (WPRT) showed better biochemical failure-free survival and metastasis-free survival than prostate-only radiotherapy (PORT) in the phase III randomized POP-RT trial for high and very high-risk prostate cancer, albeit with higher RTOG grade 2 late urinary toxicity. We report updated long term, symptom-wise comparison and dose-effect relations from this trial. Late urinary toxicity, and cumulative severity of each symptom over the follow-up period was graded using CTCAE v5.0. Grade 2+ toxicities were compared between the trial arms by chi square test. Bladder dosimetry in 5-Gy increments (V5, V10, V15...V65 Gy, V68 Gy) from the trial database of approved radiotherapy plans, was compared for each urinary symptom and overall late gr2+ toxicity by student t-test. Observed differences in dosimetric parameters were tested using multivariable logistic regression analysis, including age at diagnosis, known diabetes, tumor stage, trial arm, and prior transurethral resection of prostate (TURP). Urinary QOL scores were compared between arms using generalised linear mixed model. Combined late symptom-wise toxicity and dose-volume data were available for analysis for 193/224 patients. At a median follow-up of 75 months, cumulative CTCAE gr2+ late urinary toxicity remained higher with WPRT than PORT, though not statistically significant (36.5% vs 26.8%, p = 0.15). Grade 3 toxicity was low and similar in both arms. Symptom-wise cumulative rates showed no significant difference between arms (Table 1). Dosimetric comparison showed significantly higher bladder V5-V15 in patients with gr2+ toxicity over those with <gr2 urinary toxicity. On symptom-wise analysis, V5-V40 range was significantly higher for presence of dysuria, hematuria, and urgency. No significant differences were observed over higher dose range for any urinary symptom. On multivariable analysis, no significant association was identifiable between bladder dosimetry and urinary symptoms. Urinary QOL scores was similar between both the arms for all the symptoms. Compared to prostate-only radiotherapy, whole pelvic radiotherapy resulted similar Grade 3 urinary toxicity of about 5% with about 10% higher cumulative grade 2+ urinary toxicity over long term follow up. This difference was not reflected in patient-reported QOL. WPRT particularly increased urgency and hematuria. Larger bladder volume being irradiated with 5Gy to 15Gy dose range could contribute to increase in urinary symptoms.