Does the lymph node yield affect survival in patients with esophageal cancer receiving neoadjuvant therapy plus esophagectomy? A systematic review and updated meta-analysis

BACKGROUND: Conflicting data have been reported on the prognostic impact of the extent of lymphadenectomy during esophagectomy for esophageal cancer (EC) after neoadjuvant therapy, especially after neoadjuvant chemoradiotherapy (nCRT). METHODS: A comprehensive online search was performed to explore the association between increased lymph node yield (LNY) and survival of patients with EC, in which the overall survival (OS) was set as the primary outcome. In addition to analysis of the entire cohort, subgroup analyses of different induction therapy and different populations were also performed. FINDINGS: A total of 19528 patients from twelve studies were included in our study. The pooled data revealed that more lymph node harvested was associated with better OS (HR = 0·87; 95% CI: 0·79–0·95, p < 0·001). Notably, a higher LNY was associated with better OS if the threshold was less than 18. However, more thorough lymphadenectomy might not bring additional survival benefits when it came to a cutoff value more than 18. The subgroup analysis further revealed that a higher LNY after nCRT was associated favorable survival. In terms of subset analysis of different populations, increased LNY was associated with longer OS in Western populations but not in Eastern. INTERPRETATION: Increased LNY during esophagectomy after neoadjuvant therapy, especially after nCRT, might be associated with improved OS. More studies are warranted to assess the survival benefits of a higher LNY receiving neoadjuvant therapy plus esophagectomy, especially in Eastern populations. FUNDING: Supported by the projects from Suzhou Key Laboratory of Thoracic Oncology (SZS201907), Suzhou Key Discipline for Medicine (SZXK201803), the Science and Technology Research Foundation of Suzhou Municipality (SYS2018063, SYS2018064), Municipal Program of People's Livelihood Science and Technology in Suzhou (SS2019061) and Major Project for Social Development, Jiangsu Provincial Department of Science and Technology (SBE2020750085).