The prognostic impact of preoperative radiotherapy in stage I rectal cancer: a retrospective cohort study revealing no survival benefit from SEER database analysis.

Background: The predominant treatment modality for early-stage rectal cancer (RC) currently revolves around surgical interventions. Nonetheless, controversy persists regarding the omission of preoperative radiotherapy (RT) in early-stage patients, particularly those with T2N0M0 disease who are candidates for local excision. The debate focuses on RT's risk-benefit profile, with some evidence suggesting improved locoregional control, while other data indicate limited survival benefits alongside radiation-induced toxicity risks. This uncertainty necessitates large-scale clinical evaluations. This study aims to investigate whether preoperative RT is beneficial for stage I RC patients undergoing surgery. Methods: This retrospective cohort analysis included 16,961 stage I RC patients undergoing surgery without chemotherapy between 2004 and 2021, with follow-up through December 31, 2023, using data from population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) Program. Baseline factors included age at diagnosis, sex, RT status, year of diagnosis, stage at diagnosis, race/ethnicity, histologic type, surgical type, tumor size, and median household income. Kaplan-Meier (KM) curve analysis was used to explore the impact of preoperative RT on survival, with overall survival (OS) as the primary endpoint. Multivariate analysis of features associated with outcomes was conducted using Cox proportional hazards regression models. The 1:1 propensity score matching (PSM) analysis was conducted to balance the confounding factors. Results: The cohort was stratified into three groups: preoperative RT (n=106), postoperative RT (n=355), and no RT (n=16,500). The study suggested that RT administered before surgery did not improve OS compared to no RT in stage I cancer patients who did not undergo chemotherapy and might even be associated with worse 5-year OS rates (61.9% vs. 79.7%, P<0.001). After PSM analysis, the 5-year OS rates were 62.5% for patients with preoperative RT and 75.8% for those without RT (P=0.10). Further PSM analysis focusing on T2N0M0 and T1N0M0 data revealed that preoperative RT did not benefit T2N0M0 patients [hazard ratio (HR) =1.545; 95% confidence interval (CI): 0.975-2.45; P=0.06] and even significantly reduced OS among T1N0M0 patients (HR =2.122; 95% CI: 1.014-4.44; P=0.046). Subgroup analysis indicated that preoperative RT did not confer advantages over no RT for patients undergoing either local excision or radical resection. Conclusions: This study advocates that preoperative RT is not recommended for Stage I RC patients who do not receive chemotherapy, regardless of whether patients have undergone local excision or radical resection. Furthermore, preoperative RT offered no survival advantage to patients with T2N0M0 disease who were undergoing for local excision, and, notably, it was associated with a substantial decline in OS among patients with T1N0M0 disease. However, given limitations, including the retrospective design, lack of RT dose details, and absence of local recurrence data, further clinical trials are urgently needed to explore optimal treatment approaches for early-stage RC.