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. 2025 Sep 24.
doi: 10.1097/JS9.0000000000003546. Online ahead of print.

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

Chunji Chen  1 , Ziqiang Tian  2 , Jiangbo Lin  3   4   5 , Xuefeng Leng  6 , Jianfei Shen  7   8 , Jinbo Zhao  9 , Huilai Lv  2 , Changchun Wang  10 , Xinyu Mei  11   12 , Yongtao Han  6 , Qifeng Wang  13 , Jiahua Lv  13 , Hainan Chen  13 , Xiaolong Yan  9 , Zhichao Liu  1 , Zhengyang Zhang  3   4   5 , Qihong Zhong  3   4   5 , Youhua Jiang  10 , Liwei Xu  10 , Xiaoyang Li  12   14 , Dong Qian  12   14 , Dehua Ma  7   15 , Minhua Ye  7 , Chunguo Wang  7 , Zimin Wang  7 , Zhigang Li  1 , Xufeng Guo  1
Affiliations

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

Chunji Chen et al. Int J Surg. .

Abstract

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.

Keywords: adjuvant immunotherapy; esophageal squamous cell carcinoma; multicenter real-world study; neoadjuvant chemoimmunotherapy.

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