Work

Discordant Primary Tumor and Nodal Response After Neoadjuvant Chemoimmunotherapy Identifies an Adverse Postoperative Subgroup in Esophageal Squamous Cell Carcinoma

Year: 2026

Type: article

Abstract: BACKGROUND: Primary-tumor major pathological response (MPR) and postoperative nodal status are both used to assess response after neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC), but discordant response after neoadjuvant chemoimmunotherapy is poorly characterized. We evaluated a combined primary tumor-lymph node (PT-LN) framework for risk stratification. METHODS: This retrospective single-center cohort included patients treated with two cycles of paclitaxel, cisplatin, and camrelizumab followed by curative-intent surgery between January 2019 and December 2024. Among 414 screened patients, 367 were included. MPR was defined as 10% or less residual viable tumor cells in the primary tumor. Patients were classified as PT-MPR/ypN0, PT-MPR/ypN+, PT-non-MPR/ypN0, or PT-non-MPR/ypN+. Disease-free survival (DFS), overall survival (OS), first documented recurrence, and pathological model performance were evaluated. RESULTS: Sixty-nine patients (18.8%) had PT-MPR/ypN+ disease. DFS and OS differed across groups (both overall log-rank p < 0.001). Compared with PT-MPR/ypN0, PT-MPR/ypN+ was associated with worse DFS (baseline-adjusted hazard ratio [HR], 5.85; 95% confidence interval [CI], 2.82-12.14) and OS (HR, 18.06; 95% CI, 5.53-59.06; both p < 0.001), with similar conclusions after additional pathological adjustment. Regional lymph node recurrence occurred in 44.9% of PT-MPR/ypN+ patients versus 3.6%, 6.7%, and 16.7% in the other groups (global p < 0.001). The combined PT-LN framework had 3-year DFS and OS AUCs of 0.798 and 0.818, with modest gains over LN-only classification. CONCLUSIONS: Residual nodal disease despite primary-tumor MPR identifies an adverse phenotype with predominantly regional nodal recurrence. The combined framework is an interpretable stratification approach requiring external validation; surveillance and treatment implications remain hypothesis-generating.

Source: Cancer Medicine

DOI: 10.1002/cam4.72463