Radiation technique and outcomes following moderately hypofractionated treatment of low risk prostate cancer: a secondary analysis of RTOG 0415

Background While moderately hypofractionated radiotherapy (MHRT) for prostate cancer (PC) is commonly delivered by intensity modulated radiation therapy, IMRT has not been prospectively compared to three-dimensional conformal radiotherapy (3D-CRT) in this context. We conducted a secondary analysis of the phase III RTOG 0415 trial comparing survival and toxicity outcomes for low-risk PC following MHRT with IMRT versus 3D-CRT. Methods RTOG 0415 was a phase III, non-inferiority trial randomizing low-risk PC patients to either MHRT or conventionally fractionated radiation with stratification by RT technique. A secondary analysis for differences in overall survival (OS), biochemical recurrence free survival (BRFS), or toxicity by EPIC scores and Common Terminology Criteria for Adverse Events (CTCAE) was performed. Results 1079 patients received the allocated intervention with a median follow up of 5.8 years. 79.1% of patients were treated with IMRT and radiation technique was balanced between arms. Across all patients, RT technique was not associated with significant differences in BRFS, OS, or rates of acute and late toxicities. For patients completing MHRT, there was a difference in the late GU toxicity distribution between 3D-CRT and IMRT but no difference in late grade 2 or greater GU or GI toxicity. Stratifying patients by RT technique and fractionation, no significant differences were observed in the minimal clinically important difference (MCID) in EPIC urinary and bowel scores following RT. Conclusions RT technique did not impact clinical outcomes following MHRT for low-risk PC. Despite different late GU toxicity distributions in patients treated with MHRT by IMRT or 3D-CRT, there was no difference in late Grade 2 or greater GU or GI toxicity or patient reported toxicity. Increases in late GU and GI toxicity following MHRT compared to CFRT, as demonstrated in the initial publication of RTOG 0415, do not appear related to a 3D-CRT treatment technique.