Extended Lymphadenectomy Improves Survival After Induction Chemoradiation for Esophageal Cancer: A Propensity-Matched Analysis of the National Cancer Database

Objectives: The aim of this study was to explore the potential value of extended nodal-dissection following neoadjuvant chemoradiation (CRT), by analyzing data from the National Cancer Database (NCDB). Background: A CROSS-trial post-hoc analysis showed that the number of dissected lymph nodes was associated with improved survival in patients undergoing upfront surgery but not in those treated with neoadjuvant CRT. Methods: The NCDB was queried (2004-2014) for patients who underwent esophagectomy following induction CRT. Predictors of overall survival (OS) were assessed. The optimal number of dissected LNs associated with highest survival benefit was determined by multiple regression analyses and receiveroperating characteristic curve analysis. The whole cohort was divided into 2 groups based on the predefined cutoff number. The two groups were propensity-matched (PMs). Results: Esophagectomy following induction-CRT was performed in 14,503 patients. The number of resected nodes was associated with improved OS in the multivariable analysis (hazard ratio for every 10 nodes: 0.95 (95% confidence interval: 0.93-0.98). The cutoff number of resected LNs that was associated with the highest survival benefit was 20 nodes. In the PM groups, patients in the ≥20 LNs" group had a 14% relative-increase in OS (P= 0.002), despite having more advanced pathological stages (stage II-IV: 76% vs 72%, P <0.001), and higher number of positive nodes (0-2 vs 0-1, P < 0.001). Conclusions: The total number of resected nodes is a significant determinant of improved survival following induction CRT in patients with either node negative or node positive disease. In the matched groups, patients with higher number of resected lymph nodes had higher OS rate, despite having more advanced pathological disease and higher number of resected positive lymph nodes.