Patient-reported Outcomes from a Phase III Randomized Controlled Trial Exploring Optimal Sequencing of Short-term Androgen Deprivation Therapy with Prostate Radiotherapy in Localized Prostate Cancer.

Abstract

BACKGROUND\nTwo phase III randomized controlled trials (xxxx, RTOG-9413) and a meta-analysis have shown an impact of sequencing of androgen deprivation therapy (ADT) and radiotherapy on oncologic outcomes in prostate cancer (PCa). However, the impact of sequencing strategy on health-related quality of life (HR-QoL) is unclear. Here, we present the patient-reported HR-QoL outcomes from the xxxx study.\n\n\nMETHODS\nIn this trial, PCa patients with Gleason score ≤7, clinical stage T1b-T3a, and prostate-specific antigen <30 ng/mL were randomly assigned to neoadjuvant and concurrent ADT for 6 months starting 4 months before or concurrent and adjuvant ADT for 6 months starting simultaneously with prostate radiotherapy. HR-QoL was assessed using European Organisation for Research and Treatment of Cancer QoL questionnaires. Time until definitive deterioration was defined as time from random allocation to the first deterioration of at least 10 points with no further improvement of ≥10 points or if the patient had progression, death or dropped out after deterioration, resulting in missing data. Stratified log-rank test was applied for between-group comparisons of time-to-event estimates.\n\n\nRESULTS\nOverall, 393 patients (194 and 199 in two arms, respectively) were evaluable except 214 (101 and 113 in the two arms, respectively) for sexual function. Five-year rates of freedom from definitive deterioration of bowel symptoms, urinary symptoms, and sexual activity were 33·4%, 33·1%, and 38·5% in neoadjuvant and 34·1%, 35·4%, and 36·7% in adjuvant group, respectively with no significant between-group differences. Adjuvant approach was associated with reduced risk of definitive deterioration of sexual function (hazard ratio: 0·68, 95% confidence intervals: 0·49-0·94, p=0·02). With respect to clinical relevance, mean score change for sexual function showed only a small to moderate difference favoring adjuvant group at and beyond 3 years.\n\n\nCONCLUSIONS\nIn this study, there was no difference in the bowel or urinary symptoms between adjuvant and neoadjuvant approach. Considering a significant likelihood of type I and type II errors and due to lack of a persistent and clinically meaningful between-group difference in mean score change over time, our findings do not confer a clear and conclusive picture on impact of sequencing strategy on sexual function.