Work

Prognostic significance of lymph node staging in esophageal squamous cell carcinoma after neoadjuvant chemoimmunotherapy

Year: 2026

Type: article

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.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1931817