Patient-Reported Urinary and Bowel Quality of Life Outcomes Following External Beam Radiotherapy with or without High-Dose-Rate Brachytherapy Boost: Post-Hoc Analyses of TROG 03.04 (RADAR)

Abstract

One of the concerns with combining external beam radiotherapy (EBRT) with a high dose rate brachytherapy boost (HDRBT) for prostate cancer is increased toxicity. We aimed to evaluate long-term urinary and bowel quality of life (QoL) outcomes following EBRT vs EBRT + HDRBT using data from the TROG 03.04 trial. Men who had dose-escalated EBRT (74 Gy) or EBRT (46 Gy) + HDRBT (19.5 Gy in 3 fractions) were included in this exploratory analysis. QoL outcomes were prospectively collected using the EORTC-QLQ-PR25 at baseline, end of radiotherapy, 12, 18, 24, 36, 60 months, and annually up to 10 years. QoL score was normalized to 0-100 with higher scores representing worse symptom burden. Minimal clinically important differences (MCIDs) were defined as differences in the respective QoL scores ≥0.5 standard deviations of the baseline QoL score. Mixed models for repeated measures were used to evaluate longitudinal changes in the QoL score between EBRT and EBRT + HDRBT arms. Logistic regression was used to evaluate differences in proportion of men with 2xMCID between EBRT and EBRT + HDRBT arms at each time point. Age, baseline QoL score, ECOG performance status, and duration of androgen deprivation therapy use (6 vs. 18 months) were adjusted for in all analyses. Four hundred ninety-seven men were included in this study: 260 (52%) had EBRT and 237 (48%) had EBRT + HDRBT. The median baseline urinary QoL scores were 12.5 (IQR 4.2-19.0) and 8.3 (IQR 4.2-20.8) for men in EBRT and EBRT + HDRBT arms respectively (P = 0.5). Within the first 24 months, men in the EBRT + HDRBT arm had a slower rate of urinary QoL score resolution compared to men in the EBRT arm (P<0.001). At 12, 18, 24, and 36 months, men who had EBRT + HDRBT were 2.4 times (95% CI = 1.4-4.0; P<0.001), 3.1 times (95% CI = 1.8-5.1; P<0.001), 2.8 times (95% CI = 1.7-4.7; P<0.001), and 2.5 times (95% CI = 1.4-4.5; P = 0.002) more likely to have 2xMCID in urinary QoL scores compared to men who had EBRT alone. Beyond 24 months, there were no significant differences in the rate of urinary QoL score resolution between arms, and beyond 36 months there were no significant differences in the proportion with 2xMCID between arms. The median baseline bowel QoL score was 0 in both arms. There were no differences in the rate of bowel QoL score recovery over time between arms. Men who had EBRT + HDRBT were less likely to have 2xMCID in bowel QoL score in the immediate post-radiotherapy period (OR = 0.66; 95% CI = 0.45-0.97; P = 0.03) and at 60 months (OR = 0.51; 95% CI = 0.33-0.80; P = 0.003) compared to men who had EBRT. EBRT + HDRBT is associated with disturbances in urinary QoL that are of greater magnitude compared to EBRT alone within the first 36 months of treatment, but the differences resolved after 36 months. EBRT + HDRBT is associated with less disturbances in bowel QoL immediately after treatment and at 60 months compared to EBRT alone.