Moderate Hypofractionation in Intermediate- and High-Risk, Localized Prostate Cancer: Health-Related Quality of Life From the Randomized, Phase 3 HYPRO Trial.

PURPOSE: The phase 3 Hypofractionated Irradiation for Prostate Cancer trial compared hypofractionated radiation therapy with conventionally fractionated radiation therapy in patients with localized prostate cancer. Similar 5-year relapse-free survival rates were achieved in both groups, but noninferiority of hypofractionation was not confirmed for genitourinary and gastrointestinal toxicity. Here, we present the secondary trial endpoint on patient-reported quality of life. METHODS AND MATERIALS: A total of 820 patients with intermediate-risk or high-risk prostate cancer were randomized to hypofractionation (19 fractions of 3.4 Gy) or conventional fractionation (39 fractions of 2.0 Gy). Quality of life was measured using a validated questionnaire, the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer 25 module. Subscales (score range, 0-100) on urinary symptoms, gastrointestinal symptoms, symptoms related to androgen deprivation therapy, sexual function, and sexual activity were analyzed. Changes from baseline of at least 5 points were considered clinically relevant. Inferiority of hypofractionation for separate subscales was rejected if the mean difference in the 3-year incidence of clinically relevant deterioration between treatments was <8.0%.
RESULTS: A total of 697 men were eligible for this quality-of-life analysis. Baseline characteristics were comparable between both groups. At 3-year follow-up, the incidence of clinically relevant deterioration of urinary symptoms was 33% for both treatments (difference 0.49% in favor of conventional fractionation; 90% confidence interval, -7.20% to 8.18%). Such deterioration of gastrointestinal symptoms was reported in 38% of patients receiving hypofractionation versus 36% of patients receiving conventional fractionation (2.03% in favor of conventional fractionation; 90% confidence interval, -6.18% to 10.23%). Therefore, we could not demonstrate noninferiority of hypofractionation for genitourinary and gastrointestinal quality of life. For all other subscales, noninferiority of hypofractionation was demonstrated.
CONCLUSIONS: Noninferiority of the hypofractionated treatment was not demonstrated for genitourinary and gastrointestinal quality of life, and therefore we cannot rule out that relevant differences may exist between both treatments. Noninferiority of hypofractionation was demonstrated for symptoms related to androgen deprivation therapy, sexual activity, and sexual function.

RCT Entities:   Population Interventions Outcomes