Lymph node dissection in neoadjuvant chemoimmunotherapy for locally advanced esophageal squamous cell carcinoma: A multicenter real-world study.

Abstract

The optimal extent of lymph node dissection (LND) following neoadjuvant chemoimmunotherapy (NCIT) for esophageal squamous cell carcinoma (ESCC) remains unclear, with concerns regarding postoperative immunosuppression and survival benefit. A multicenter retrospective cohort study was conducted across 8 high-volume centers, including 724 patients with locally advanced ESCC who underwent NCIT followed by esophagectomy between January 2019 and March 2023. The number of total LNDs was modeled as a continuous variable using restricted cubic splines, and the optimal LND threshold for overall survival (OS) was determined using maximally selected rank statistics ("maxstat" package in R), identifying 19 nodes as the cut-off. Patients were grouped into LND ≤19 and LND >19. The primary endpoint was 2-year OS; secondary endpoints included 2-year disease-free survival (DFS), postoperative complications, recurrence, and distant metastasis. Multivariable Cox regression adjusted for clinicopathologic variables. The median patient age was 61.0 years (interquartile range, 56.0-67.0 years); 79.8% were male. Patients with LND >19 had significantly better 2-year OS compared with those with LND ≤19 (83.6% vs 77.8%; hazard ratio [HR], 1.56, 95% confidence interval [CI], 1.13-2.15; P < .001). There was no significant difference in 2-year DFS (76.2% vs 73.5%; HR, 1.09; 95% CI, 0.80-1.50; P = .187). Rates of locoregional recurrence (13.3% vs 18.0%; P = .083) and distant metastasis (13.5% vs 13.8%; P = .922) were similar. Overall complication rates did not differ significantly (56.5% vs 48.7%; P = .073), although higher incidences of pneumonia (P < .001), anastomotic leak (P = .012), and recurrent laryngeal nerve palsy (P = .018) were observed in the LND >19 group. Dissection of >19 lymph nodes after NCIT is associated with improved 2-year OS without increasing overall morbidity, supporting systematic LND in modern ESCC management.