Differences in toxicity and outcome associated with circadian variations between patients undergoing daytime and evening radiotherapy for prostate adenocarcinoma

This retrospective study tested the hypothesis that disease control and treatment-related toxicity in patients undergoing high-dose radiotherapy (HDRT) for prostate cancer varies in a circadian manner. Patients with localized prostate adenocarcinoma receiving HDRT (median 78 Gy) to the prostate and involved seminal vesicle(s) without elective pelvic irradiation were divided into a daytime treatment (before 5 PM) group (<i>n</i> = 267) and evening treatment (after 5 PM) group (<i>n</i> = 142). Biochemical failure (Phoenix definition), acute and late gastrointestinal (GI) and genitourinary toxicities (Common Terminology Criteria for Adverse Events version 4), biochemical failure-free survival (BFFS) and freedom from late toxicity were assessed. Analyses were performed by binary logistic regression and Cox proportional hazard regression. The median follow-up was 68 months, and 75% of patients were ≥70 years old. Evening HDRT was significantly associated with worse freedom from ≥grade 2 late GI complications (hazard ratio = 2.96; <i>p</i> &lt; 0.001). The detrimental effect of evening HDRT was significant in patients older than 70 years old (<i>p</i> &lt; 0.001) but not in younger patients (<i>p</i> = 0.63). In a subgroup of propensity score-matched cohort with T2b–T3 disease (<i>n</i> = 154), the 5-year BFFS was worse in the evening group than the daytime group (72% vs. 85%, hazard ratio = 1.95, <i>p</i> = 0.05). Our study indicates that evening HDRT may lead to more GI complications, especially in older patients, and worse BFFS in patients with T2b–T3 disease.