Immunotherapy-based adjuvant treatment after neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma according to pathological response

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Background: Neoadjuvant immunochemotherapy (NICT) is increasingly used in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). However, optimal postoperative adjuvant treatment strategies remain unclear. This study aimed to evaluate the efficacy of immunotherapy-based adjuvant treatment in patients with ESCC after NICT according to pathological response status. Methods: We retrospectively analyzed 260 patients with locally advanced ESCC who underwent radical resection after NICT between 2019 and 2023. Patients were first stratified by pathological response status [pathological complete response (pCR) vs. non-pCR], and immunotherapy-based adjuvant treatment was subsequently compared with observation within each stratum. Baseline imbalances were adjusted using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Disease-free survival (DFS) and overall survival (OS) were assessed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards models. Results: Of the 260 patients, 84 (32.3%) achieved pCR, and 81 (31.2%) received immunotherapy-based adjuvant treatment. The median follow-up was 36.8 months. In the pCR cohort, immunotherapy-based adjuvant treatment did not significantly improve 3-year DFS or OS compared with observation (80.8% vs. 90.1%, P = 0.065; 96.2% vs. 91.8%, P = 0.486), with consistent results in the PSM and IPTW analyses. In the overall non-pCR cohort, immunotherapy-based adjuvant treatment likewise did not confer significant survival benefits (3-year DFS: 71.9% vs. 58.1%, P = 0.120; 3-year OS: 83.3% vs. 75.3%, P = 0.155), and the adjusted analyses yielded similar findings. Exploratory subgroup analyses suggested a potential survival benefit among non-pCR patients with pathological downstaging (3-year DFS: 82.5% vs. 57.6%, P = 0.028; 3-year OS: 93.8% vs. 72.6%, P = 0.022). Further analysis showed no significant differences in 3-year DFS or OS between adjuvant immunotherapy alone and adjuvant immunochemotherapy among non-pCR patients with pathological downstaging (83.3% vs. 81.7%, P = 0.890; 91.7% vs. 94.7%, P = 0.988). Conclusions: Among patients with ESCC treated with NICT, immunotherapy-based adjuvant treatment did not improve survival in those who achieved pCR or in the overall non-pCR population. A potential benefit was observed in non-pCR patients with pathological downstaging. In this subgroup, adjuvant immunotherapy alone and adjuvant immunochemotherapy showed comparable efficacy.

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