Adjuvant immunotherapy for esophageal squamous cell carcinoma after neoadjuvant chemoimmunotherapy: a multicenter real-world study

Background: Although adjuvant immunotherapy demonstrated an improvement in disease-free survival (DFS) within the chemoradiotherapy cohort of the CheckMate 577 trial, its efficacy and role following NCIT remain to be elucidated. This large-sample, multicenter, real-world study aims to assess survival benefits of adjuvant immunotherapy in esophageal squamous cell carcinoma (ESCC) patients treated with neoadjuvant chemoimmunotherapy (NCIT) followed by R0 resection. Methods: This multicenter retrospective study (8 centers, Jan 2019–Mar 2023) included 724 ESCC patients undergoing NCIT and R0 resection. Propensity score matching (PSM) balanced 262 patients per group: NCIT + Surgery (NCIT + S) vs. NCIT + Surgery + adjuvant immunotherapy (NCIT + S + ICI). Primary endpoints were 2-year overall survival (OS) and DFS; secondary endpoints included recurrence patterns. Findings: Median follow-up: 31.2 months (IQR 24.0–39.9). Post-PSM analysis showed no significant OS benefit (2-year OS: 80.0% vs. 84.5%, HR = 1.15, 95% CI:0.78–1.70, p = 0.12) or DFS improvement (77.7% vs. 72.6%, HR = 0.97, 95% CI:0.69–1.37, p = 0.69) for NCIT + S vs. NCIT + S + ICI. Adjuvant immunotherapy was not independently protective for OS (HR = 0.87, p = 0.48) or DFS (HR = 1.03, p = 0.87). However, subgroup analyses revealed OS benefits in Non-MPR patients (63.9% vs. 81.7%, HR = 1.78, 95% CI:1.05–3.03, p = 0.035) and Non-pCR patients (74.9% vs. 84.3%, HR = 1.39, 95% CI:1.19–2.10, p = 0.031). Recurrence rates did not differ (local:15.3% vs.20.2%, p = 0.50; distant:16.8% vs.21.6%, p = 0.17). Interpretation: Adjuvant immunotherapy provided no survival benefit in the overall NCIT-treated ESCC cohort but improved OS in patients with residual tumor (Non-MPR/Non-pCR). Further studies are warranted to refine patient selection for adjuvant immunotherapy in this setting.