ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Gastric and Esophageal Cancers
A Pathological Classification for Predicting Recurrence and Guiding Adjuvant Therapy in Esophageal Squamous Cell Carcinoma following Neoadjuvant Immunochemotherapy: a Two-Center Cohort Study
Provisionally accepted
- 1Jinan University, Guangzhou, China
- 2Jieyang People's Hospital, Jieyang, China
- 3Shenzhen People's Hospital, Jinan University, Shenzhen, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Neoadjuvant immunochemotherapy (nICT) has emerged as a promising treatment modality for locally advanced esophageal squamous cell carcinoma (ESCC). However, optimal post-nICT adjuvant strategies remain undefined, and a classification system that integrates both prognosis and recurrence patterns to guide treatment decisions is currently lacking. Methods: This retrospective study enrolled 283 patients with locally advanced ESCC who underwent nICT with R0 resection between January 2019 and December 2023 at two participating institutions. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included recurrence patterns, overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). Survival curves were generated using the Kaplan-Meier method. Propensity score matching was employed for group comparisons and a Cox proportional hazards model was used to identify prognostic factors. Results: The pathological complete response (pCR) and major pathological response (MPR) rates were 22.6% and 52.3%, respectively. Multivariate analysis identified the tumor regression grade (TRG) and ypN stage as independent predictors of RFS. Both ypN status and TRG were key determinants of recurrence patterns. Based on this, patients were stratified into four subgroups: Group 1 (TRG0-1 ypN0), Group 2 (TRG0-1 ypN+), Group 3 (TRG2-3 ypN0), and Group 4 (TRG2-3 ypN+). This classification demonstrated significant prognostic stratification, with Group 1 having the best prognosis and Group 4 having the worst prognosis. In the entire matched cohort, adjuvant therapy did not significantly improve survival. However, subgroup analyses revealed that adjuvant therapy was associated with a significant improvement in RFS in Group 2 (TRG0-1 ypN+)(HR = 0.16, 95% CI 0.06–0.42, P＜0.001). Conclusion: The proposed classification system based on TRG and ypN status effectively stratified the prognosis of patients with ESCC after nICT. This classification enabled the identification of a specific subgroup (TRG0-1 ypN+) that may benefit from postoperative adjuvant treatment. Keywords: Esophageal squamous cell carcinoma, neoadjuvant immunotherapy, chemotherapy, adjuvant therapy, recurrence pattern, pathological response
Keywords: adjuvant therapy, chemotherapy, esophageal squamous cell carcinoma, neoadjuvant immunotherapy, Pathological response, Recurrence pattern
Received: 31 Dec 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Huang, Xie, Zeng, Yao, Zhang, Zhang and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qijun Zheng
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.