Abstract
PURPOSE: For stage II and III rectal cancer, two commonly used treatment strategies are preoperative radiotherapy (RT) combined with surgery, and surgery combined with postoperative RT. This study aims to systematically compare the efficacy of preoperative RT versus postoperative RT for rectal cancer based on the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Cases of rectal cancer were retrieved using SEER ∗ Stat software, including patients who underwent preoperative RT combined with surgery (PreORT group) and those received surgery combined with postoperative RT (PostORT group). Propensity score matching (PSM) was performed via the R software package (version 4.3.1) to balance intergroup differences. Kaplan–Meier curves for overall survival (OS) and cause-specific survival (CSS) were plotted for the cohort before and after PSM using IBM SPSS 23.0. RESULTS: A total of 22,079 rectal cancer cases were included, with 16,719 in the PreORT group and 5,360 in the PostORT group. Compared with the PostORT group, the PreORT group showed significantly higher 10-year OS (54.5% Vs. 58.9%, P < 0.001) and CSS (64.5% Vs. 67.9%, P < 0.001). However, in the matched cohort, the PostORT group had higher 10-year OS (55.7% Vs. 57.4%, P = 0.038) and CSS (64.8% Vs. 67.5%, P = 0.040). CONCLUSION: While the PreORT group exhibited higher OS and CSS in the entire cohort, the PostORT group showed favorable survival outcomes in the matched cohort. However, given that PreORT remains the standard of care and SEER data lack critical clinical variables influencing treatment selection, these findings should be interpreted as hypothesis-generating rather than indicative of a change in clinical practice. Future randomized, multicenter, prospective studies with large sample sizes are therefore warranted to validate these results and identify subgroups most likely to benefit from each approach. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-026-04701-1.