Robot-assisted oesophagectomy shows non-inferior survival in oesophageal squamous cell carcinoma

BACKGROUND: Robot-assisted minimally invasive oesophagectomy is used increasingly worldwide. However, no large-scale, multicentre, randomised controlled trial has compared long-term survival as the primary endpoint between robot-assisted oesophagectomy and conventional thoracoscopic oesophagectomy. We aimed to confirm the non-inferiority in overall survival of robot-assisted oesophagectomy over thoracoscopic oesophagectomy in patients with resectable oesophageal squamous cell carcinoma. METHODS: This multicentre, open-label, randomised, controlled, phase 3, non-inferiority trial (RAMIE) was conducted at six hospitals in China. Patients aged 18-75 years, with biopsy-proven squamous cell carcinoma, Eastern Cooperative Oncology Group scores of 0-2, and with tumour and nodal classifications of cT1-4a, N0-2, M0, or M1 (supraclavicular lymph nodes metastasis) were eligible. Patients were randomly assigned (1:1) using a computer-generated randomisation list and stratified by neoadjuvant therapy to robot-assisted oesophagectomy or thoracoscopic oesophagectomy, both with at least two-field lymphadenectomy. The primary endpoint was overall survival, analysed in the intention-to-treat population. The non-inferiority margin was 9% for 5-year overall survival (the upper limit of 95% CI of the hazard ratio [HR] was 1·33). Harms were assessed in the per-protocol population, defined as all eligible participants undergoing resection. This trial was registered with ClinicalTrials.gov, number NCT03094351 and is completed. FINDINGS: Between Aug 2, 2017, and Dec 23, 2019, 362 patients were randomly assigned (183 to robot-assisted oesophagectomy and 179 to thoracoscopic oesophagectomy. 309 (85%) of 362 patients were men and 53 (15%) were women. Two patients in each group did not undergo resection and were excluded from the per-protocol population. Median follow-up of the planned final analysis was 71·5 months (IQR 63·9-81·8). At 5 years, overall survival was 69·4% (95% CI 62·1-75·6) with robot-assisted oesophagectomy versus 56·2% (48·5-63·2) with thoracoscopic oesophagectomy (HR 0·71, 95% CI 0·51-0·97), confirming non-inferiority (one-sided p=0·0001; exploratory analysis of p=0·032 for superiority). Intraoperative conversions to open surgery were similar between study groups (seven [4%] of 181 patients in the robot-assisted group vs six [3%] of 177 in the thoracoscopic group). Postoperative grade 3 or higher complications were comparable (22 [12%] of 181 patients in the robot-assisted group vs 18 [10%] of 177 in the thoracoscopic group). One treatment-related death occurred in each group. INTERPRETATION: In patients with resectable oesophageal squamous cell carcinoma, robot-assisted oesophagectomy was non-inferior, and seemed superior, to thoracoscopic oesophagectomy in terms of 5-year overall survival. FUNDING: National Clinical Key Specialty Construction Project, Shanghai Hospital Development Center, and the Program of Shanghai Academic/Technology Research Leader. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.