BACKGROUND: The optimal extent of lymphadenectomy following neoadjuvant chemoimmunotherapy (nCIT) for esophageal squamous cell carcinoma (ESCC) remains unclear. Current recommendations are largely derived from neoadjuvant chemoradiotherapy cohorts, and their applicability in the era of immunotherapy is unclear. This study evaluated the association between lymph node dissection (LND) yield and disease-free survival (DFS) in patients with ESCC treated with nCIT. METHODS: This retrospective multicenter cohort study included 465 patients with ESCC who underwent nCIT followed by radical esophagectomy at six hospitals in China between January 2019 and December 2023. The median follow-up was 40.7 months. The total number of dissected lymph nodes was analyzed in relation to DFS. The restricted mean survival time at 5 years was estimated by using random survival Forest-based models, with subgroup analyses by posttherapy pathological stage (ypT/ypN). RESULTS: A higher lymph node yield was associated with improved DFS, although the relationship was nonlinear and varied by pathological subgroup. In patients with ypT0-2N0 disease, DFS improved with increasing LND up to approximately 20-30 lymph nodes, after which the benefit plateaued. In patients with residual nodal disease (ypN1-3), higher lymph node yields were associated with longer DFS, with greater yields observed in more advanced disease stages. Across all subgroups, lower lymph node yields were consistently associated with inferior DFS. CONCLUSIONS: In this multicenter cohort of patients with ESCC treated with nCIT, lymph node yield was associated with DFS in a stage-dependent manner, suggesting its potential role as a postoperative quality indicator for surgical lymphadenectomy after nCIT.
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