Background: Minimally invasive surgery (MIS) is associated with improved perioperative safety outcomes, but, in 2018, the Laparoscopic Approach to Cervical Cancer (LACC) trial, a non-inferiority study comparing laparoscopic versus open radical hysterectomy for early stage cervical cancer, reported significantly worse disease-specific (DSS) and overall survival (OS) in the MIS group. Criticisms of the LACC trial include lack of proper preoperative imaging and assessment, use of transcervical uterine manipulators, and lack of proper tumor containment leading to peritoneal contamination. Subsequent retrospective studies have reported conflicting results. Given the potential benefit of MIS, the ROCC trial seeks to address the limitations of the LACC trial. Methods: ROCC is a multi-center, prospective, randomized, non-inferiority trial. The primary objective is to determine whether robotic-assisted (RBT) radical hysterectomy is not inferior to abdominal (OPEN) approach with respect to 3-year disease-free survival (DFS). Secondary objectives include DSS, OS, patterns of recurrence, peri- and postoperative complications, long-term morbidity, impact on patient-reported outcome (PRO) measures and development of lower extremity lymphedema (LEL). Key inclusion criteria include patients with histologically confirmed adenocarcinoma, squamous cell, and adenosquamous cell carcinoma of FIGO 2018 stage IA2-IB2. All patients must have a preoperative pelvic MRI confirming that the cervical tumor is < 4 cm in size, no obvious evidence of extracervical extension and no nodal or other regional metastasis. Intraoperatively, the use of transcervical uterine manipulators is not allowed and specific detailed surgical techniques for proper tumor containment is required. Photographic evidence of specimen with tumor contained is mandated. We estimate the 3-year DFS to be 92% in the control (OPEN) arm. If the DFS does not differ by more than 7% and the one-sided 95% CI does not cross the non-inferiority boundary, then the RBT arm will be deemed non-inferior. 840 patients will be enrolled (420 per arm, 89 events total), which provides 90% power to exclude an absolute decrease in DFS by 7% (HR < = 1.375) with a log-rank test for non-inferiority with a one-sided alpha of 0.05. The primary analysis will be conducted in all randomized patients (ITT). Given the LACC findings of worse oncologic outcomes with MIS, a formal DSMC will conduct periodic reviews of safety including two planned formal interim analyses for futility (harm) after accrual of 370 and 640 patients using an aggressive Lan-DeMets beta-spending function similar to a Pocock boundary. Results of this trial may be practice changing and will either support or refute the findings of the LACC trial. The study is currently activating sites for enrollment. Clinical trial information: NCT04831580.