Prognostic significance of lymph node staging in esophageal squamous cell carcinoma after neoadjuvant chemoimmunotherapy
- 1Medical School of Chinese PLA
- 2Department of Thoracic Surgery, The First Medical Centre, Chinese PLA General Hospital
- 3School of Medicine, Nankai University
Abstract
Background: Neoadjuvant chemoimmunotherapy (nCIT) has emerged as a standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the independent prognostic value of postoperative pathological N stage (ypN) and to assess whether pre-treatment clinical N stage (cN) provides additional prognostic information in patients achieving ypN0.
Methods: We retrospectively analyzed 194 ESCC patients who received nCIT followed by radical esophagectomy between January 2019 and December 2024. Patients were stratified into three groups: cN0/ypN0 (n=104), cN+/ypN0 (n=32), and ypN+ (n=58). Kaplan-Meier analysis and Cox proportional hazards models were used for survival analysis. Multivariable models were constructed using a clinically informed variable-selection strategy constrained by the number of events. For the three pairwise comparisons, unadjusted P values were compared against a Bonferroni-adjusted significance threshold of alpha=0.017 (0.05/3).
Results: A total of 194 patients were enrolled, with 31 deaths and 37 recurrences during a median follow-up of 34.0 months (reverse Kaplan–Meier). ypN+ patients had significantly worse overall survival (OS) and recurrence-free survival (RFS) than ypN- patients (both Log-rank P<0.001). In the primary multivariable model, ypN+ was an independent adverse prognostic factor for OS (HR = 3.204, 95%CI: 1.563-6.568, P = 0.001) and RFS (HR = 3.780, 95%CI: 1.943-7.356, P<0.001), and remained robust across extended, cycle-adjusted, and landmark sensitivity analyses. Among the three groups, ypN+ showed significantly shorter OS compared with both ypN0 groups (P = 0.002 vs cN0/ypN0; P = 0.008 vs cN+/ypN0; both below the Bonferroni threshold) and shorter RFS compared with cN0/ypN0 (P<0.001). No significant difference was observed between cN0/ypN0 and cN+/ypN0 groups for OS (P = 0.259); the RFS comparison was nominally significant but did not survive Bonferroni correction (HR = 2.799, 95%CI: 1.048-7.479, unadjusted P = 0.040).
Conclusion: Postoperative ypN stage is the core prognostic determinant in ESCC after nCIT. In patients achieving ypN0, pre-treatment cN did not demonstrate statistically significant additional prognostic discrimination in this cohort, although estimates were imprecise due to the small cN+/ypN0 subgroup and limited events. Postoperative risk assessment should be based primarily on ypN status; these findings require validation in larger, preferably multicenter, cohorts.
Related
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BibTeX
@article{han2026prognostic,
title = {{Prognostic significance of lymph node staging in esophageal squamous cell carcinoma after neoadjuvant chemoimmunotherapy}},
author = {Herui Han and Xiaobin Hou and Yiming Liu and Wenhan Cai and Jiamei Jin and Xiangming Qiu and Zirui Zhu and Kai Zhao and Mingchuan Hu and Zhiqiang Xue},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1931817},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1931817/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Prognostic significance of lymph node staging in esophageal squamous cell carcinoma after neoadjuvant chemoimmunotherapy
AU - Herui Han
AU - Xiaobin Hou
AU - Yiming Liu
AU - Wenhan Cai
AU - Jiamei Jin
AU - Xiangming Qiu
AU - Zirui Zhu
AU - Kai Zhao
AU - Mingchuan Hu
AU - Zhiqiang Xue
PY - 2026
DA - 2026/10/23
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1931817
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1931817/full
AB - Background: Neoadjuvant chemoimmunotherapy (nCIT) has emerged as a standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the independent prognostic value of postoperative pathological N stage (ypN) and to assess whether pre-treatment clinical N stage (cN) provides additional prognostic information in patients achieving ypN0. Methods: We retrospectively analyzed 194 ESCC patients who received nCIT followed by radical esophagectomy between January 2019 and December 2024. Patients were stratified into three groups: cN0/ypN0 (n=104), cN+/ypN0 (n=32), and ypN+ (n=58). Kaplan-Meier analysis and Cox proportional hazards models were used for survival analysis. Multivariable models were constructed using a clinically informed variable-selection strategy constrained by the number of events. For the three pairwise comparisons, unadjusted P values were compared against a Bonferroni-adjusted significance threshold of alpha=0.017 (0.05/3). Results: A total of 194 patients were enrolled, with 31 deaths and 37 recurrences during a median follow-up of 34.0 months (reverse Kaplan–Meier). ypN+ patients had significantly worse overall survival (OS) and recurrence-free survival (RFS) than ypN- patients (both Log-rank P<0.001). In the primary multivariable model, ypN+ was an independent adverse prognostic factor for OS (HR = 3.204, 95%CI: 1.563-6.568, P = 0.001) and RFS (HR = 3.780, 95%CI: 1.943-7.356, P<0.001), and remained robust across extended, cycle-adjusted, and landmark sensitivity analyses. Among the three groups, ypN+ showed significantly shorter OS compared with both ypN0 groups (P = 0.002 vs cN0/ypN0; P = 0.008 vs cN+/ypN0; both below the Bonferroni threshold) and shorter RFS compared with cN0/ypN0 (P<0.001). No significant difference was observed between cN0/ypN0 and cN+/ypN0 groups for OS (P = 0.259); the RFS comparison was nominally significant but did not survive Bonferroni correction (HR = 2.799, 95%CI: 1.048-7.479, unadjusted P = 0.040). Conclusion: Postoperative ypN stage is the core prognostic determinant in ESCC after nCIT. In patients achieving ypN0, pre-treatment cN did not demonstrate statistically significant additional prognostic discrimination in this cohort, although estimates were imprecise due to the small cN+/ypN0 subgroup and limited events. Postoperative risk assessment should be based primarily on ypN status; these findings require validation in larger, preferably multicenter, cohorts.
SN - 2234-943X
ER -