Extent of Lymphadenectomy Is Associated With Improved Overall Survival After Esophagectomy With or Without Induction Therapy

Abstract

National Comprehensive Cancer Network (NCCN) guidelines recommend sampling 15 or more lymph nodes during esophagectomy. The proportion of patients meeting this guideline is unknown, as is its influence on overall survival (OS). Univariate analysis and logistic regression were performed to identify variables associated with sampling 15 or more lymph nodes among patients undergoing esophagectomy in the National Cancer Data Base (NCDB). The NCCN guideline was evaluated in Cox proportional hazards modeling, along with alternative lymph node thresholds. Positive to examined node (PEN) ratios were calculated, and OS was compared using Kaplan-Meier analysis. From 2006 to 2012, only 6,961 of 18,777 (37.1%) patients undergoing esophagectomy had sampling of 15 or more lymph nodes. Variables associated with sampling 15 or more lymph nodes included income greater than or equal to $38,000, procedure performed in an academic facility, and increasing clinical T and N stages. Induction therapy was associated with a decreased likelihood of 15 or more lymph nodes being sampled. The largest decrease in mortality hazard in patients undergoing upfront esophagectomy was detected when 25 lymph nodes or more were sampled (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.67-0.89; p < 0.001), whereas for patients undergoing induction therapy, sampling of 10 or 15 or more lymph nodes was associated with optimal survival benefit (HR, 0.81; 95% CI, 0.74-0.90; p < 0.001). PEN ratios of 0 to 0.10 were associated with maximum survival benefit among all patients undergoing esophagectomy. For patients with a PEN ratio of 0, increases in OS were detected with higher lymph node sampling (85.3 months for sampling of 20 or more lymph nodes versus 52.0 months for sampling 1-9 lymph nodes; p < 0.001). For patients undergoing upfront esophagectomy, there may be an increased survival benefit for examining 20 to 25 lymph nodes, which is higher than current recommendations. However, only a minority of patients are meeting current guidelines.