PATIENTS UNDERGOING minimally invasive radical hysterectomy for early cervical cancer had higher rates of disease recurrence and worse disease-free, progression-free, and overall survival than did women who had the open approach, according to results from the phase III LACC trial, presented by Pedro T. Ramirez, MD, of The University of Texas MD Anderson Cancer Center in Houston, at the 2018 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in New Orleans.1
“Disease-free survival at 4.5 years for minimally invasive radical hysterectomy was inferior compared with the open approach,” said Dr. Ramirez. “The results of this trial should be discussed with patients scheduled to undergo radical hysterectomy.”
“Disease-free survival at 4.5 years for minimally invasive radical hysterectomy was inferior compared with the open approach. The results of this trial should be discussed with patients scheduled to undergo radical hysterectomy.”— Pedro T. Ramirez, MD
Tweet this quote
In more than 600 patients, the number of disease recurrences after laparoscopic or robotic-assisted procedures was nearly 4 times higher than that of recurrences after abdominal surgery—27 vs 7—and significantly more patients who had minimally invasive surgery died during a median follow-up of 2.5 years—19 vs 3 with open surgery.
Thirty-three centers around the world participated in the LACC trial, designed to test for noninferiority of total laparoscopic or robotic radical hysterectomy compared with standard-of-care total abdominal radical hysterectomy for early-stage cervical cancer. It is the largest prospective randomized trial comparing these two modalities for radical hysterectomy.
Conflicting Data
The data from the trial starkly contrast with what’s in the literature, Dr. Ramirez noted. For instance, in a trial of 1,539 patients, laparoscopic radical hysterectomy was associated with a reduction in blood loss, postoperative complications, and hospital stays compared with the open approach, with no significant differences in 5-year disease-free and overall survival.2
Similarly, an analysis of more than 4,000 cases showed that robotic radical hysterectomy was associated with less blood loss, lower transfusion rates, lower wound-related complications, and shorter hospital stays than open radical hysterectomy.3
Key Findings in LACC Trial
The LACC trial had a primary endpoint of disease-free survival at 4.5 years. Participating centers were required to submit 10 minimally invasive surgery cases—either laparoscopic or robotic-assisted procedures—to a trial management committee in advance of the trial, as well as 2 unedited videos of minimally invasive procedures to demonstrate surgical proficiency.
SURGICAL APPROACHES TO EARLY CERVICAL CANCER
- Unexpected results of a phase III trial revealed worse overall survival and higher rates of recurrence with minimally invasive vs open radical hysterectomy for early cervical cancer.
- The intention-to-treat analysis showed a 4.5-year disease-free survival rate of 96.5% in the open-surgery group and 86% in the minimally invasive arm.
- According to the investigators, the results of this trial should be discussed with patients scheduled to undergo radical hysterectomy.
Eligible patients had stage IA1 to IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix. The trial opened in June 2008 and accrued 631 patients, and it closed to new patient accrual in June 2017, when the data and safety monitoring committee performed an interim analysis and on subsequent data analysis performed in September 2017, it recommended unblinding the study because of higher rates of recurrence and mortality in the minimally invasive treatment arm. The data for the primary outcome were about 60% complete at the time of the analysis, and the data for overall survival were 54% complete.
A total of 312 patients underwent total abdominal radical hysterectomy, and 319 patients had the minimally invasive procedure. There were no significant differences in postoperative histopathology between the two cohorts, except in the depth of invasion, with a higher rate of superficially invasive tumors in the minimally invasive group. There was also a slight difference in terms of the median number of lymph nodes between the two groups, but no difference in the rate of positive lymph nodes was observed.
Disease-free survival was significantly worse for patients who underwent minimally invasive surgery, Dr. Ramirez reported. The intention-to-treat analysis showed a 4.5-year disease-free survival rate of 96.5% in the open-surgery group and 86% in the minimally invasive arm. A per-protocol analysis showed 4.5-year disease-free survival rates of 97.6% and 87.1%, respectively. ■
DISCLOSURE: Dr. Ramirez reported no conflicts of interest.
REFERENCES
1. Ramirez PT, Frumovitz M, Pareja R, et al: Phase III randomized trial of laparoscopic or robotic versus abdominal radical hysterectomy in patients with early-stage cervical cancer: LACC trial. 2018 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer. LBA1. Presented March 26, 2018.
2. Wang YZ, Deng L, Xu HC, et al: Laparoscopy versus laparotomy for the management of early stage cervical cancer. BMC Cancer 15:928, 2015.
3. Shazly SA, Murad MH, Dowdy SC, et al: Robotic radical hysterectomy in early stage cervical cancer: A systematic review and meta-analysis. Gynecol Oncol 138:457-471, 2015.
