The roles of neoadjuvant radiotherapy and lymphadenectomy in the treatment of esophageal adenocarcinoma

Objective: Using a population-based registry, we evaluated the impact of neoadjuvant radiotherapy and lymphadenectomy on survival of patients undergoing curative-intent surgery for esophageal adenocarcinoma (EAC). Methods: Surveillance, Epidemiology, and End Results (SEER) data for patients with esophageal adenocarcinoma from 1988 to 2005 were queried. Patients undergoing curative operations were included. Treatment was stratified between no radiotherapy, neoadjuvant versus adjuvant radiotherapy, and adequate (≥18 lymph nodes) versus inadequate (<18 lymph nodes) lymphadenectomy. Univariate and multivariate analysis were performed to determine median survival (MST) and cause-specific survival (CSS). Results: Overall, 4,224 patients underwent surgical extirpation with curative intent for EAC in the study period. MST and CSS for the entire cohort were 25 and 31 months, respectively. Multivariate analysis showed age <65 years, well-differentiated tumor, local disease, negative lymph node status, adequate lymphadenectomy, and neoadjuvant radiotherapy to be independent predictors of improved survival. In node-positive patients, the greatest survival benefit was seen in patients who received both neoadjuvant radiotherapy and adequate lymphadenectomy (MST = 32 months, CSS = 34 months). The lymph node ratio (LNR) for adequately dissected patients treated with neoadjuvant radiotherapy was 0.17, which is <0.2, the established LNR cutoff that is an independent predictor of improved survival. The survival benefit of neoadjuvant treatment is additive to that of adequate lymphadenectomy. Conclusion: There is a cooperative survival benefit for neoadjuvant radiation and adequate lymphadenectomy in patients with node-positive EAC. Both are independent predictors of improved survival. Patients who have clinically node-positive disease should undergo both neoadjuvant radiation and adequate lymphadenectomy to ensure optimal outcome.