BACKGROUND

Circadian rhythms regulate critical cellular processes, including DNA repair and cell cycle dynamics, potentially influencing the effectiveness of radiotherapy (RT). This study evaluated whether RT timing impacts clinical outcomes and symptom burden in prostate cancer patients.

PATIENTS/METHODS: This retrospective study ( = 336, median follow-up 55 months) included men who received curative intent external beam RT between 2010 and 2019 (median age 69, 69% black, median PSA 11.3, 40% with Gleason 8-10). Treatment times (TTs) were averaged and analyzed by quartile/median. Outcomes included freedom from biochemical failure (FFBF) and distant metastasis (FFDM), GI and GU toxicity, and quality of life (QOL). Subgroup analyses by race and hormone therapy status were performed.

RESULTS

Across the overall cohort, TT was not associated with FFBF or FFDM. However, in white men, earlier TTs were significantly associated with higher 5-year FFBF (89% vs. 67%, = 0.0139) and FFDM (93% vs. 72%, = 0.0268). In the multivariate analysis (MVA), TT was not associated with FFBF or FFDM for all men, but in white men, earlier TT was associated with improved FFBF (HR 2.8, = 0.06) in a model also including risk category ( = 0.21). Overall, no significant differences were observed for grade 2-3+ toxicity and TT. Trends for inferior QOL, and worse grade 2+ ( = 0.2) and 3+ GU toxicity ( = 0.1) were observed for later TTs. In white men, bowel, urinary continence, and irritative/obstructive urinary QOL were worse with later TTs ( < 0.05).

CONCLUSIONS

TT may influence clinical outcomes and symptom burden, particularly in white men. These findings underscore the potential of chronoradiotherapy as a personalized treatment strategy and highlight the need for prospective trials.