Prognostic Stratification of Adjuvant Immunotherapy After Neoadjuvant Chemoimmunotherapy and Quality Surgery in LA-ESCC

BACKGROUND: In locally advanced esophageal squamous cell carcinoma (LA-ESCC), neoadjuvant chemoimmunotherapy (NCIT) plus high-quality surgery (R0 resection with systematic lymphadenectomy >19 nodes) is a promising strategy. However, the value of adjuvant immunotherapy remains unclear. This study aimed to evaluate the association between postoperative adjuvant immunotherapy and survival outcomes in a multicenter cohort. METHODS: This multicenter retrospective study enrolled LA-ESCC patients receiving NCIT from eight high-volume Chinese centers between 2019 and 2023. After screening for high-quality surgery, propensity score matching (PSM) balanced characteristics between the two groups: NCIT plus surgery (NCIT+S) and NCIT plus surgery followed by adjuvant immunotherapy (NCIT+S+ICI). The primary endpoints were overall survival (OS) and disease-free survival (DFS). A prognostic framework based on major pathological response (MPR) and postoperative pathological N stage (ypN) was constructed to refine patient selection. RESULTS: Among 724 patients with a median follow-up of 40.3 months, 3-year OS and DFS rates were 73.0% and 67.7%, respectively. After PSM, adjuvant immunotherapy significantly improved DFS (77.1% vs 65.8%, log-rank P=0.037), but not OS (83.4% vs 69.4%, log-rank P=0.058). Multivariate analysis identified ypN, MPR, and postoperative adjuvant immunotherapy as independent prognostic factors for DFS. Stratification by MPR and ypN status showed that DFS benefit from adjuvant immunotherapy was restricted to the non-MPR/ypN+ subgroup (HR=0.339; 95% CI: 0.173-0.662; log-rank P<0.001), with a significant treatment-by-subgroup interaction (P for interaction=0.025). CONCLUSIONS: Among LA-ESCC patients receiving NCIT and high-quality surgery, adjuvant immunotherapy significantly improves 3-year DFS in the non-MPR/ypN+ subgroup, with no significant benefit in other subgroups.