DOI: 10.32322/jhsm.1991234 ISSN: 2636-8579

Association of neoadjuvant treatment-initiation season with pathological response and survival in locally advanced rectal cancer

Mustafa Serkan Alemdar, Selami Bayram
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Aims: Seasonal variation in sunlight exposure has been linked to cancer prognosis, but whether the season of initiating neoadjuvant treatment affects outcomes in locally advanced rectal cancer is unknown. We examined its association with pathological response and survival.Methods: We retrospectively analysed 156 patients with locally advanced rectal cancer treated with long-course neoadjuvant chemoradiotherapy and total mesorectal excision at two centres (2014-2025). Patients were grouped by the month of treatment initiation into high-insolation (April-September; n=79) and low-insolation (October-March; n=77) periods. Pathological complete response (pCR), overall survival (OS), and recurrence-free survival (RFS) were compared, and prognostic factors were assessed by Cox regression.Results: The groups were balanced except for older age in the low-insolation group. A pCR occurred in 26 patients (16.7%), without a significant difference between high- and low-insolation groups [13.9%, 95% confidence interval (CI) 6.3-21.6 vs. 19.5%, 95% CI 10.6-28.3; p=0.395]. Over a median follow-up of 55.5 months, season was not associated with OS (5-year 65.9% vs. 58.7%; log-rank p=0.434) or RFS (5-year 56.5% vs. 54.5%; p=0.477); these results were unchanged after multivariable adjustment [OS: hazard ratio (HR) 1.18, p=0.574; RFS: HR 1.22, p=0.443]. Independent predictors were older age and an R1 margin for OS, and older age, lower rectal location, 5-fluorouracil, and lymphovascular invasion for RFS.Conclusion: In this Mediterranean cohort, the season of initiating neoadjuvant chemoradiotherapy was not associated with pathological response or survival; established pathological features remained the principal determinants of outcome. Confirmation in larger, multicentre studies across different latitudes is warranted.

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