Comparative effectiveness of five treatment strategies for locally advanced oral squamous cell carcinoma in resource-limited settings: a multinomial overlap-weighted real-world cohort study

Background and objective For locally advanced oral squamous cell carcinoma (LA-OSCC), radical surgery followed by risk-adapted postoperative radiotherapy or concurrent chemoradiotherapy is standard. In resource-limited settings, limited radiotherapy access, costs, and poor tolerance yield multiple pragmatic strategies. Prior real-world studies mostly used pairwise comparisons, lacking systematic evaluation of all coexisting strategies within one framework. Methods This single-center retrospective cohort study included 388 patients with LA-OSCC treated between January 2019 and December 2022, classified into five groups by actual treatment received: surgery with adjuvant chemoradiotherapy (surgery plus CRT), surgery with adjuvant radiotherapy (surgery plus RT), surgery with adjuvant chemotherapy (surgery plus CT), surgery alone, and definitive chemoradiotherapy (CRT). Multinomial overlap weighting targeting the average treatment effect in the overlap population (OW-ATO) balanced 10 baseline covariates, and overlap-weighted Cox models with robust variance estimation compared overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS). Two-group (surgery versus definitive CRT) and four-group (operated patients, pathology-adjusted) analyses, competing-risk models, and sensitivity analyses (IPTW-ATE, landmark, early-death exclusion, E-value, bootstrap) assessed robustness. Results After overlap weighting, the maximum absolute pairwise standardized mean difference decreased from 0.548 to 0.168. Compared with surgery plus CRT, surgery plus RT showed no statistically significant differences in OS (hazard ratio [HR] 1.33, 95% CI 0.76–2.33), DFS (HR 1.23, 95% CI 0.79–1.90), or DSS (HR 1.56, 95% CI 0.77–3.15), whereas surgery plus CT (OS HR 2.54, 95% CI 1.47–4.39), surgery alone (OS HR 3.21, 95% CI 1.94–5.32), and definitive CRT (OS HR 3.31, 95% CI 1.97–5.57) were each associated with significantly worse outcomes across all three endpoints. Findings were consistent across all analytical layers and sensitivity analyses. Conclusions In resource-limited real-world settings, surgery-based multimodal strategies were associated with better survival in LA-OSCC. Surgery plus RT did not differ significantly from surgery plus CRT; however, given wide confidence intervals and limited power, equivalence was not established, and it should be considered only a potential de-escalation option for selected patients who cannot receive concurrent chemotherapy—not as a replacement for standard chemoradiotherapy in high-risk disease. Surgery plus CT should be reserved as a second-best option when radiotherapy is completely unavailable.