Association of clinical response and lymph node yield with prognosis after neoadjuvant therapy for esophageal...

The optimal extent of lymphadenectomy after neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC) remains uncertain. We hypothesized that preoperative clinical response modifies the prognostic value of lymph node (LN) yield.

We conducted a two-center retrospective cohort study of consecutive patients with locally advanced ESCC treated at two high-volume esophageal cancer centers in China between January 2018 and August 2023. A total of 729 patients who received neoadjuvant therapy followed by R0 McKeown esophagectomy and systematic lymphadenectomy were included. Clinical response was assessed preoperatively using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and patients were stratified as responders or non-responders. LN yield was modeled primarily as a continuous exposure (per 10 additional nodes) using Cox models with multivariable adjustment and stabilized inverse probability of treatment weighting (sIPTW). Nonlinearity was assessed using spline models. Secondary analyses evaluated incremental nodal yield and postoperative complications.

Among 729 patients, 456 were responders and 273 were non-responders. Median follow-up was 41 months. The association between LN yield and survival differed significantly by clinical response. In non-responders, higher LN yield was associated with improved overall survival (OS) and recurrence-free survival (RFS) (both adjusted hazard ratio (HR) per 10 nodes, 0.66), whereas no clear survival association was observed in responders (OS: 1.07; RFS: 1.10); interaction was significant for both endpoints. Incremental nodal detection was greatest at lower LN-yield ranges and diminished thereafter. Higher LN yield was also associated with increased risks of severe postoperative complications, pleural effusion, and recurrent laryngeal nerve palsy.

The prognostic value and clinical trade-offs of lymphadenectomy after neoadjuvant therapy may differ by preoperative clinical response. These findings support prospective validation of response-adapted surgical strategies in ESCC.