Robot-assisted Minimally Invasive Thoraco-laparoscopic Esophagectomy Versus Minimally Invasive Esophagectomy for Resectable Esophageal Cancer, a Randomized Controlled Trial (ROBOT-2 Trial).

Aim of the study This is a randomized controlled parallel-group, superiority trial comparing RAMIE to MIE with intrathoracic anastomosis (Ivor-Lewis) in patients with resectable esophageal adenocarcinoma or adenocarcinoma of the gastroesophageal junction in the Western World.

Methods Objectives Patients with resectable esophageal adenocarcinoma or adenocarcinoma of the gastroesophageal junction are randomized at the outpatient department to either (a) robot-assisted minimally invasive esophagectomy (RAMIE) or (b) conventional minimally invasive esophagectomy (MIE). The objective is to evaluate the extent of lymph node dissection, efficacy, risks, survival and cost-effectiveness of RAMIE as an alternative to MIE as treatment for esophageal adenocarcinoma or adenocarcinoma of the gastroesophageal junction. We hypothesize that RAMIE leads to an improved lymph node dissection compared to MIE.

Study design This is a multicenter investigator-initiated and investigator-driven randomized controlled parallel-group, superiority trial comparing RAMIE to MIE. This study is conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice Guidelines. The independent ethics committee of the University Medical Center of the Johannes Gutenberg University, Mainz, Germany has approved the study. Written informed consent will be obtained from all participating patients. All centers participating in the ROBOT-2 trial have extensive experience in minimally invasive esophageal surgery and have an experience with at least 50 MIE an 50 RAMIE procedures performed.

Clinical trial monitoring will be conducted by an independent data monitor from the Johannes Gutenberg University, Mainz, Germany. A Data safety monitoring board (DSMB) will evaluate safety for patients included within this trial. All outcomes will be evaluated by a (blinded) external independent data committee board for the Upper GI International Robotic association (UGIRA).

Study protocol Patients are informed about the trial by one of our surgeons at the outpatient department. After receiving the information, all patients get one week time to consider their consent. After obtaining informed consent, randomization, with concealment of allocation, is done centrally by an online randomization program. There is no blinding for the patient, surgeon and coordinating researcher because this is difficult in daily practice. However the UGIRA committee and DSMB are blinded to the allocated intervention. This study is funded by Intuitive surgical Inc., Sunnyvale, CA, USA. Neoadjuvant (radio)chemotherapy will be administered according to current international policy. Multiple esophageal cancer biopsies for pathological analysis will be obtained through esophagogastroscopy of which 4 biopsies will be snap frozen and stored for translational research. All resection specimens will be preserved and stored (biobank) for translational research. The study will start on April 1st 2020. Inclusion will take approximately 2 years. Follow up for each patient will be 5 years. Total duration of the study will be 7 years.