Routinely collected health data on 10-year genitourinary and gastrointestinal morbidity after ultra-hypofractionated versus conventionally fractionated radiotherapy for localised prostate cancer in the randomised, non-inferiority, phase 3 trial HYPO-RT-PC.

[BACKGROUND AND PURPOSE] HYPO-RT-PC was the first phase 3 trial showing the long-term efficacy and safety of extremely hypofractionated radiotherapy schedules (ultra-hypofractionation or stereotactic body radiotherapy) compared with standard radiotherapy in localised prostate cancer. We aimed to verify their safety in the context of a clinical trial, by comparing events of potentially radiotherapy-related morbidity according to routinely collected health data between the arms and with men unexposed to prostate radiotherapy.

[MATERIALS AND METHODS] We included Swedish residents in the per-protocol population and unexposed men matched with the ultra-hypofractionation group. Primary outcomes were genitourinary and gastrointestinal events defined by linking the Common Terminology Criteria for Adverse Events version 5.0 to diagnosis and intervention codes in broad (any related condition) and narrow code sets (strongly related conditions) tested separately. Inpatient care, interventions, and causes of death, identified in Swedish national healthcare registers, were events. Outcomes were analysed as time-to-event, adjusted for Charlson Comorbidity Index and socioeconomic status.

[RESULTS] Five hundred and forty-one participants (92%) from each trial arm and 2705 unexposed men were included. We found no statistically significant differences between the radiotherapy groups (broad code sets: genitourinary events, adjusted hazard ratio 0.95, 95% confidence interval 0.71-1.25; gastrointestinal events, 1.24, 0.91-1.69). Compared with the unexposed men, 10-year excess cumulative incidence was 8% and 5% for genitourinary and 5% and 4% for gastrointestinal events when applying the broad and narrow code sets, respectively, without excess mortality events.

[CONCLUSION] The results support the HYPO-RT-PC findings by showing similar morbidity between ultra-hypofractionated and standard radiotherapy. Excess events were estimated to 4-8%, without increased associated mortality.