Abstract
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) poses significant therapeutic challenges, with poor prognosis despite standard treatments including neoadjuvant chemoradiotherapy or chemotherapy. Emerging evidence suggests that adding immune checkpoint blockade to conventional chemotherapy—referred to as neoadjuvant immunochemotherapy (nICT)—enhances pathologic tumor regression; however, real-world data regarding long-term survival outcomes remain limited. METHODS: This single-center retrospective study analyzed data from 204 patients with locally advanced ESCC treated between January 2019 and September 2022. Patients received either neoadjuvant chemotherapy (nCT; n = 95) or nICT (n = 109). To address baseline imbalances, stabilized inverse probability of treatment weighting (sIPTW) based on propensity scores was applied. The primary endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: The median duration of follow-up was 36.7 months (95% confidence interval [CI], 33.8-39.6 months). After applying sIPTW, compared to the nCT group, the nICT group exhibited significantly improved OS (hazard ratio [HR], 0.49; 95% CI, 0.26-0.91; P = .03) and DFS (HR, 0.58; 95% CI, 0.35-0.95; P = .04). The 3-year OS and DFS rates were 84.3% and 69.8%, respectively, in the nICT group and 68.8% and 58.1%, respectively, in the nCT group. In the nICT group, pathologic complete response (pCR) and major pathologic response (MPR) were associated with reduced risk of recurrence and death. CONCLUSIONS: nICT was associated with improved OS and DFS in patients with locally advanced ESCC. Higher rates of pCR and MPR were correlated with better survival outcomes. These findings support the integration of immunotherapy into neoadjuvant treatment strategies, although prospective trials remain necessary for validation.