The Prognostic Impact of Lymph Node Yield Upon Survival in Esophageal Cancer Broken Down by Neoadjuvant Strategy: A Multicenter European Cohort Study

Objective: To establish a lymph node yield (LNY) change-point associated with improvements in overall survival (OS) and disease-free survival (DFS) in patients undergoing esophagectomy following neoadjuvant treatment for esophageal adenocarcinoma. Secondary endpoints include recurrence patterns and survival based on pathological staging. Summary background data: LNY has been associated with improved outcomes in esophageal cancer. The extent of lymphadenectomy following neoadjuvant treatment remains unclear. Methods: This multicenter European study included patients undergoing chemotherapy (CT) or chemoradiotherapy (CRT) followed by esophagectomy between 2018 and 2023. RA-CUSUM analysis identified change points between LNY and survival. Bootstrap resampling determined the optimal LNY, and multivariable Cox proportional hazards models analyzed LNY as continuous and categorical variables. A post hoc exploratory subgroup analysis was conducted in CT patients with optimal LNY compared with CRT irrespective of LNY. Recurrence patterns were assessed using the Fisher exact test. Results: A total of 2069 patients were included: 957 CT versus 1112 CRT. Median LNY was 32. CT data set: an optimal threshold of 25 nodes was identified (95% CI: 20-39). Categorical analysis using ≥25 nodes demonstrated 29% mortality reduction (HR: 0.714, P=0.0017). CRT data set: no significant LNY association across any endpoint. Continuous LNY showed a null effect (P=0.633), and categorical analysis showed no benefit (P=0.66). CT with ≥25 LNY had ∼44% lower mortality compared with CRT after adjustment for potential confounding variables (HR=0.563, P<0.001). Each positive LN increased the hazard for death by 7.3% in CT and 11.2% in CRT. Disease recurrence occurred in 32.7% of CT versus 38.3% of CRT (P=0.001). Conclusion: On the basis of this data, there is a clear survival and recurrence benefit to performing a radical lymphadenectomy with a lymph node harvest of at least 25 nodes in patients who have received CT.