Nadia Guidozzi, Wing K. Chou, Lorenzo Giorgi, Riadh Salem, Stijn Vanstraelen, Helena Gielen, Johnny Moons, Philippe Nafteux, Femke E. Lammes, Jelle P. Ruurda, Richard van Hillegersberg, Alban Todesco, Xavier B. D’Journo, Alice Collizzolli, Barbara Ajazi, Simone Giacopuzzi, Maria Bencivenga, Sam Alhayo, Ella Seabourne, Ewen A. Griffiths, Aram Abu Hejleh, Lars M. Schiffmann, Christiane J. Bruns, Giovanni M. Garbarino, Andrea Pansa, Silvia Basato, Ophélie Bacoeur-Ouzillou, Caroline Gronnier, Sofie P. G. Henckens, Suzanne S. Gisbertz, Rakesh Ahmed, Nithiesh Loganathan, Jessie A. Elliott, Kirsty Cole, Youssef Ibrahim, Chanakya Anand, Philip H. Pucher, Martin Skogar, Jakob Hedberg, Eloise Bonnin, Julie Veziant, Guillaume Piessen, Agnese Carresi, Silvia Battaglia, Francesco Puccetti, Riccardo Rosati, Fahad Murad, Fredrik Klevebro, Magnus Nilsson, Grard A.P. Nieuwenhuijzen, Lars van de Sanden, Misha D.P. Luyer, Rita Alfieri, Carlo Castoro, Mark I. van Berge Henegouwen, Sheraz R. Markar
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.