ROCC/GOG-3043: A randomized non-inferiority trial of robotic versus open radical hysterectomy for early-stage cervical cancer.

Abstract

TPS5605 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.

Trends in Early-Stage Cervical Cancer Management in the US: A National Cancer Database Analysis

“…Since the publication of the LACC trial, debate has ensued regarding the mechanism of the shortened survival associated with and the potential safe utilization of MIS for appropriate candidates [2,4,10]. The choice of surgical modality is also influenced by resource availability and various socioeconomic factors.…”

Clinical practice guidelines for cervical cancer: the Korean Society of Gynecologic Oncology guidelines

“…The most significant reason for the decreased survival rate in minimally invasive radical hysterectomy compared to open radical hysterectomy is believed to be tumor cell spillage caused by the uterine manipulator or CO 2 gas used during the minimally invasive surgical procedure [ 11 12 ]. Various efforts have been made to prevent tumor cell spillage during MIS, such as vaginal cuff closure and uterine extraction using a retrieval bag, uterine extraction through vaginal colpotomy [ 11 ], vaginal cuff resection using a laparoscopic stapler [ 13 ], and the no-look-no-touch technique [ 14 ] with several comparative clinical studies based on these efforts [ 15 16 17 18 ]. Additionally, in the LACC trial, there was no difference in survival rates between the MIS and open surgery groups when conization was performed before radical hysterectomy (HR=1.27; 95% CI=0.39–4.17; p=0.69) and similar results have been reported in several retrospective studies [ 19 20 ].…”

Challenges in the Diagnosis and Individualized Treatment of Cervical Cancer

“…Studies aimed at reproving the safety of minimally invasive surgery for cervical cancer have been initiated and are currently in progress. Among the leading points of criticism of the LACC trial are the use of transcervical uterine manipulators, the lack of proper tumor containment at the time of colpectomy leading to peritoneal contamination, non-comparable operators/expertise, a low prevalence of robotic-assisted radical hysterectomy and the lack of proper preoperative imaging and assessment [ 23 , 24 , 25 , 26 ].…”

“…The results of this study are eagerly awaited [ 34 ]. Likewise, the ongoing Robotic versus Open Radical Hysterectomy for Cervical Cancer (ROCC) trial will provide more detailed insights into this currently critical issue [ 23 ].…”