ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
The Neoadjuvant Esophageal (NAE) Score: A Prognostic Tool for Predicting Survival and Postoperative Complications in Esophageal Squamous Cell Carcinoma
Provisionally accepted
Hao Chen1Xuan Huang2Cheng Huang1
Qichang Xie1Chun Chen1
Bin Zheng1Yuxing Lin2
Renjie Huang3Li Cheng4Chi Xu1*
Zhang Yang1,5*- 1Fujian Medical University Union Hospital, Fuzhou, China
- 2Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
- 3Fuzhou Pulmonary Hospital of Fujian, Fuzhou, China
- 4The Second Hospital of Zhangzhou, Zhangzhou, China
- 5Physical Examination Center, Fujian Medical University Union Hospital, Fuzhou, China
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Background: Esophageal squamous cell carcinoma (ESCC) remains a major global health challenge, and reliable prognostic markers. We developed and validated the Neoadjuvant Esophageal (NAE) score, derived from treatment response, to predict overall survival (OS) and postoperative complications in locally advanced ESCC. Methods: We retrospectively analyzed 411 patients with ESCC from four hospitals who underwent esophagectomy following neoadjuvant therapy between July 2013 and November 2020. Patients were stratified into low-, intermediate-, and high-score groups. OS was assessed using Kaplan–Meier and Cox regression analyses, and predictive models were constructed with nomograms. Model performance was evaluated using concordance index (C-index), ROC curves, calibration plots, and decision curve analysis. Results: The NAE score effectively stratified survival outcomes (5-year OS, p<0.001), with higher scores indicating worse prognosis. Adjuvant therapy provided a significant OS benefit only in the high-NAE group (p=0.044), but not in the low-or intermediate-score groups. Multivariable Cox analysis confirmed the NAE score, perineural invasion, lymphovascular invasion, and neutrophil count as independent prognostic factors. A survival nomogram incorporating these variables demonstrated strong discrimination (C-index=0.742) and superior predictive accuracy compared with TNM staging (AUC 0.673–0.835 vs. 0.618–0.725). In addition, a complication-prediction nomogram integrating NAE score, surgical approach, and alcohol consumption reliably predicted major postoperative complications (C-index=0.789). Conclusion: The NAE score is a robust prognostic tool for patients with locally advanced ESCC, capable of predicting survival, guiding adjuvant therapy, and estimating risk of severe postoperative complications. Its integration into clinical practice could refine risk stratification and support personalized treatment strategies, with prospective validation warranted.
Keywords: esophageal squamous cell carcinoma, Neoadjuvant Therapy, Prognostic score, overall survival, Postoperative Complications
Received: 16 Sep 2025; Accepted: 01 Dec 2025.
Copyright: © 2025 Chen, Huang, Huang, Xie, Chen, Zheng, Lin, Huang, Cheng, Xu and Yang. 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:
Chi Xu
Zhang Yang
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