To evaluate the impact of preoperative chemoradiotherapy on long-term survival in patients aged≥75 years with locally advanced rectal cancer (LARC).

This retrospective cohort study utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients aged≥75 years with pathologically confirmed stageⅡ-Ⅲ rectal adenocarcinoma who underwent surgery between January 2010 and December 2020. Patients were stratified into two groups: the neoadjuvant chemoradiotherapy group and the surgery-alone group. Propensity score matching (PSM) balanced baseline characteristics between groups. Primary endpoints included overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier curves estimated survival rates, with Log-Rank tests comparing between-group differences. COX proportional hazards models identified factors associated with OS and generated hazard ratios (HR) with 95%confidence intervals (CI). The Fine-Gray competing risk model evaluated CSS and calculated subdistribution hazard ratios (sHR)with 95%CI. Sensitivity analyses including multivariable adjustment in the whole-cohort, inverse probability weighting, and overlap weighting were performed.

All of 605 patients enrolled, 419 received preoperative chemoradiotherapy and 186 underwent surgery alone. After 1:1 PSM, 147 matched pairs demonstrated well-balanced baseline characteristics. Median OS was not reached in the preoperative chemoradiotherapy group (95%CI: 49.0 to not reached) versus 43.0 months (95%CI: 35.0-52.0) in the surgery alone group (P < 0.01). Multivariate COX regression identified preoperative chemoradiotherapy as independently associated with reduced all-cause mortality (HR=0.531, 95%CI: 0.363-0.775, P < 0.01). Non-cancer deaths comprised 40.9% of all deaths. Fine-Gray competing risk analysis demonstrated 26.7% reduction in cancer-specific mortality with preoperative chemoradiotherapy (sHR=0.733, 95%CI: 0.451-1.193, P > 0.05), although this did not reach statistical significance. In the whole-cohort multivariable adjustment analysis, neoadjuvant chemoradiotherapy was associated with significantly better OS (HR=0.498, 95%CI: 0.363-0.682, P < 0.01) and CSS (sHR=0.571, 95%CI: 0.378-0.861, P < 0.01) compared with the surgery alone. Inverse probability weighting and overlap weighting analyses yielded consistent results.

Patients aged≥75 years with LARC derive significant OS benefit from preoperative chemoradiotherapy. Advanced age alone should not preclude this treatment approach.