Association of immune-related adverse events with survival outcomes in esophageal squamous cell carcinoma following neoadjuvant chemoimmunotherapy: a national multicenter retrospective cohort study in China

Although immune-related adverse events (irAEs) are increasingly recognized as biomarkers of response to immunotherapy in advanced cancers, their prognostic role in the neoadjuvant setting for esophageal squamous cell carcinoma (ESCC) remains unclear. This retrospective multicenter cohort study aimed to evaluate the associations between irAEs, pathological response, and 2-year survival outcomes in patients with locally advanced ESCC treated with neoadjuvant chemoimmunotherapy (NCIT) followed by esophagectomy. A total of 1076 patients with cT1bN1-3 M0 or cT2-4aN0-3 M0 ESCC who received NCIT and surgery between January 2019 and March 2023 across 26 tertiary centers in China were included. IrAEs, defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, were observed in 181 patients (16.8%), with rash/pruritus being the most common. Patients who developed irAEs completed fewer NCIT cycles and had longer treatment-to-surgery intervals, both of which were independently associated with worse disease-free survival (DFS). Although the occurrence of irAEs correlated with inferior overall survival (OS)-particularly pneumonitis and rash/pruritus-multivariable analysis revealed that irAEs were not independent predictors of either OS or DFS. The strongest independent predictors of survival were pathological nodal status (ypN3) and poor tumor regression (TRG4). In conclusion, despite being linked to prolonged treatment-to-surgery intervals, irAEs were not significantly associated with pathological response or long-term survival outcomes in this cohort of ESCC patients treated with NCIT and surgery, underscoring the importance of effective management of irAEs during neoadjuvant therapy.

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Publication Details

Journal
Diseases of the Esophagus
Published
2026-01-04
DOI
https://doi.org/10.1093/dote/doaf137
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
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article

Association of immune-related adverse events with survival outcomes in esophageal squamous cell carcinoma following neoadjuvant chemoimmunotherapy: a national multicenter retrospective cohort study in China

Y L Chen, Chunji Chen, W. Wang, C. Chen et al.
Diseases of the Esophagus
Cancer Immunotherapy and Biomarkers
article

Association of immune-related adverse events with survival outcomes in esophageal squamous cell carcinoma following neoadjuvant chemoimmunotherapy: a national multicenter retrospective cohort study in China

Y L Chen, Chunji Chen, W. Wang, C. Chen, X. B. Li, S. Liu, Junhui Fu, Yegang Ma, Jun Yi, Tao Jiang, Ziqiang Tian, L. Chen, Zhigang Li, Y. Han, Jianhong Lian, Bentong Yu, Yousheng Mao, Jianqun Ma, Chang Yuan, Yin Li, Weidong Hu, Qixun Chen, Guangjian Zhang, Lijie Tan, Xinyu Mei, Li Wei, Keneng Chen, Hui Tian
article en

Abstract

Although immune-related adverse events (irAEs) are increasingly recognized as biomarkers of response to immunotherapy in advanced cancers, their prognostic role in the neoadjuvant setting for esophageal squamous cell carcinoma (ESCC) remains unclear. This retrospective multicenter cohort study aimed to evaluate the associations between irAEs, pathological response, and 2-year survival outcomes in patients with locally advanced ESCC treated with neoadjuvant chemoimmunotherapy (NCIT) followed by esophagectomy. A total of 1076 patients with cT1bN1-3 M0 or cT2-4aN0-3 M0 ESCC who received NCIT and surgery between January 2019 and March 2023 across 26 tertiary centers in China were included. IrAEs, defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, were observed in 181 patients (16.8%), with rash/pruritus being the most common. Patients who developed irAEs completed fewer NCIT cycles and had longer treatment-to-surgery intervals, both of which were independently associated with worse disease-free survival (DFS). Although the occurrence of irAEs correlated with inferior overall survival (OS)-particularly pneumonitis and rash/pruritus-multivariable analysis revealed that irAEs were not independent predictors of either OS or DFS. The strongest independent predictors of survival were pathological nodal status (ypN3) and poor tumor regression (TRG4). In conclusion, despite being linked to prolonged treatment-to-surgery intervals, irAEs were not significantly associated with pathological response or long-term survival outcomes in this cohort of ESCC patients treated with NCIT and surgery, underscoring the importance of effective management of irAEs during neoadjuvant therapy.

Diseases of the EsophagusVol. 39(1)
Hebei Medical University (CN), University of Science and Technology of China (CN), Fujian Medical University (CN), Nanchang University (CN), Harbin Medical University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Sichuan University (CN), Shanghai Chest Hospital (CN), Shantou University (CN), Wuhan University (CN), Zhengzhou University (CN), Thoracic Surgery Foundation (US), National Cancer Center (US), West China Hospital of Sichuan University (CN), Huaian First People’s Hospital (CN), Zhejiang Cancer Hospital (CN), Shanxi Provincial Cancer Hospital (CN), Third Affiliated Hospital of Harbin Medical University (CN), Fourth Hospital of Hebei Medical University (CN), Wuhan No.1 Hospital (CN), Hunan Cancer Hospital (CN), Sichuan Cancer Hospital (CN), Zhongnan Hospital of Wuhan University (CN), First Affiliated Hospital of Xi'an Jiaotong University (CN), Zhongshan Hospital (CN), Henan Provincial People's Hospital (CN), Second Affiliated Hospital of Nanjing Medical University (CN), Shantou Central Hospital (CN), Anyang Institute of Technology (CN), Fujian Provincial Cancer Hospital (CN), Union Hospital (US), Tang Du Hospital (CN), First Affiliated Hospital of Zhengzhou University (CN), Liaoning Cancer Hospital & Institute (CN), Qilu Hospital of Shandong University (CN), Beijing Haidian Hospital (CN), Anyang Tumor Hospital (CN), Union Hospital (CN), First Affiliated Hospital of Nanchang University (CN), Nanjing Medical University (CN), China Medical University (CN)
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Cancer Immunotherapy and Biomarkers
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