Safety and efficacy study of laparoscopic or robotic radical surgery using an endoscopic stapler for inhibiting tumour spillage of cervical malignant neoplasms evaluating survival (SOLUTION): a multi-centre, open-label, single-arm, phase II trial protocol

Abstract

Background The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer. Methods This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%. Discussion We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery. Trial registration ClinicalTrials.gov; NCT04370496; registration date, May 2020.

Radical Hysterectomy for Early Stage Cervical Cancer

“…The pattern of recurrence is another proof of concept of the possible tumor dissemination at the time of colpotomy [ 32 ]. Patients undergoing laparoscopic radical hysterectomy are more likely to experience intrapelvic recurrence and develop peritoneal carcinomatosis in comparison with patients undergoing open surgery [ 32 , 33 ].…”

Effect of modified radical laparoscopic hysterectomy versus open radical hysterectomy on short-term clinical outcomes in early-stage cervical cancer: a single-center, prospective, randomized controlled trial

“…(3) The complete resection (tumor-free) principle was strictly implemented in this trial. Previous studies have identified an association between positive vaginal excision margins and an increased risk of early-stage cervical cancer recurrence along residual vaginal tissue [ 11 , 28 , 29 ]. To further ensure the safety of vaginal resection margins in the experiment, the additional resected vaginal margins with staples were sent for secondary pathological examination.…”

“…The sample size was calculated according to the method specified in the previous study [ 11 ]. The 4.5-year DFS rate of patients undergoing radical hysterectomy for abdominal cervical cancer is estimated to be 90%.…”

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 ].…”