Three-field vs two-field lymphadenectomy in thoracic ESCC patients: a multicenter randomized study (NST 1503).

3-field lymph node dissection (3FL) frequently lead to much more perioperative complications than 2-field lymph node dissection (2FL). This study was designed as a non-inferiority trial to evaluate whether 3FL could be omitted without compromising overall survival (OS) and disease-free survival (DFS) in the patients with resectable thoracic esophageal squamous cell cancer (ESCC) and negative right recurrent laryngeal nerve lymph nodes (RRLN-LNs). cT1b-3N0-1M0 thoracic ESCC patients were managed in 3 arms during open or minimally invasive McKeown esophagectomy according to the results of frozen section examination for RRLN-LNs: if positive, direct 3FL (RRLN[+]-3FL); if negative, 2FL (RRLN[-]-2FL) or 3FL (RRLN[-]-3FL) by randomization. Based on frozen section, of the 829 finally recruited patients, 121 (13.6 %) had positive RRLN-LNs and direct 3FL (RRLN[+]-3FL); 766 had negative RRLN-LNs and were randomized into the RRLN [-]-2FL (386 cases) or RRLN[-]-3FL (380 cases) group. The cervical LN metastasis rate in the RRLN[+]-3FL group (28.9 %) was significantly higher than that in the RRLN[-]-3FL group (8.3 %) (P<0.001). The 5-year OS and DFS were 72.2 % and 65.1 % in the RRLN[-]-3FL group and 68.8 % and 62.8 % in the RRLN[-]-2FL group (OS, P = 0.163; DFS, P = 0.378), versus 50.3 % and 41.2 % in the RRLN[+]-3FL group (both P<0.001), respectively. Additional cervical lymphadenectomy can be avoided in the patients with middle or lower thoracic ESCC and negative RRLN-LNs by frozen section treated by upfront surgery.Trial Registration: ClinicalTrials.gov Identifier NCT02448953.