Patient-reported Quality of Life in PROFIT, a Phase 3 Randomized Clinical Trial Evaluating Moderately Hypofractionated Radiotherapy for Intermediate-risk Prostate Cancer.

Background and objective: The PROFIT trial was designed to compare moderately hypofractionated (HF) radiotherapy versus conventional fractionation (CF) for patients with intermediate-risk prostate cancer (IR-PC). Similar efficacy and toxicity outcomes were previously reported. The aim of the current analysis was to evaluate differences in long-term patient-reported outcomes (PROs) between the HF and CF arms in PROFIT.

Methods: For the PROFIT phase 3 randomized clinical trial, patients with IR-PC (n = 1206) were enrolled from 14 sites in Canada, 12 in Australia, and one in France and randomized to receive 78 Gy in 39 fractions over 8 wk (CF) or 60 Gy in 20 fractions over 4 wk (HF). PROs were evaluated at baseline and 24 and 48 mo using the Expanded Prostate Cancer Index Composite, American Urological Association Symptom Score (AUASS), and the 12-item Short Form Health Survey (SF-12) comprising a physical component summary (PCS) and a mental component summary (MCS). A minimally important difference (MID) was defined as a deterioration in domain- or subdomain-specific health-related quality of life (HRQoL) score by ≥0.5 times the standard deviation at each time point in comparison to baseline. Statistical significance was set at p < 0.01.

Key findings and limitations: AUASS results were similar and stable over time in both arms (median 5 points, interquartile range 2-9; p > 0.2). There were no significant differences in scores for urinary, bowel, sexual, and hormonal domains or subdomains between the arms at any time point (p > 0.02). The greatest decline over time occurred in sexual domain, with a decrease of ≥10 points from baseline to 24 mo in both arms. SF-12 mean scores for both PSC and MSC were similar in the two arms and remained stable at all time points. The only significant differences in the proportion of patients reporting MIDs were for the bowel subdomains at 48 mo, with significant MID reductions favoring HF for both the bowel summary score (53% vs 44%; p = 0.01) and bowel function score (51% vs 39%; p = 0.001). Overall treatment satisfaction was high in both arms: ≥88% of patients were either satisfied or extremely satisfied with their treatment.

Conclusions and clinical implications: PRO results from the PROFIT trial suggest no significant differences in urinary, bowel, sexual, hormonal, and general HRQoL between CF and HF radiotherapy schedules. This study provides level 1 evidence supporting the use of moderate HF radiotherapy as standard treatment in patients with IR-PC. This trial is registered on ClinicalTrials.gov as NCT00304759.