# Radiation Chronotherapy in Prostate Cancer: Does Time of Day of Radiation Treatment Influence Disease Outcome or Symptom Burden?

## TL;DR

This study suggests that the time of day radiation therapy is given may affect prostate cancer outcomes and quality of life, especially in white men.

## Contribution

The study reveals that radiation treatment timing may influence clinical outcomes and symptom burden in prostate cancer patients, particularly in white men.

## Key findings

- Earlier radiation treatment times were associated with better freedom from biochemical failure and distant metastasis in white men.
- Later treatment times correlated with worse quality of life in white men, though no overall toxicity differences were observed.
- Chronoradiotherapy may serve as a personalized treatment strategy, highlighting the need for further prospective trials.

## Abstract

Radiation treatment time may impact radiation response differently by race. In this retrospective single-institutional study of 336 men with prostate cancer treated with EBRT, white men treated earlier in the day had better freedom from biochemical failure and distant metastasis. No clear differences in toxicity or quality of life were appreciated overall, but worse quality of life was observed for later treatment times in white men.

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 (n = 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%, p = 0.0139) and FFDM (93% vs. 72%, p = 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, p = 0.06) in a model also including risk category (p = 0.21). Overall, no significant differences were observed for grade 2–3+ toxicity and TT. Trends for inferior QOL, and worse grade 2+ (p = 0.2) and 3+ GU toxicity (p = 0.1) were observed for later TTs. In white men, bowel, urinary continence, and irritative/obstructive urinary QOL were worse with later TTs (p < 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.