New data confirm that an open surgical approach is preferable to minimally invasive surgery for the treatment of early-stage cervical cancer and should be considered the standard of care.
The current standard surgical approach for cervical cancer stages IA2 to IB2 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 is open radical hysterectomy and lymph node staging.
Pedro Ramirez, MD, of Houston Methodist Hospital, and colleagues reported the final results of the prospective, non-inferiority randomized laparoscopic trial of open versus minimally invasive radical hysterectomy for the treatment of cervical cancer (LACC). “Given the higher recurrence rate and poorer overall survival with minimally invasive surgery, an open approach should be the standard of care,” the team concluded in the Journal of Clinical Oncology.
In the following interview, Ramirez, head of the Department of Obstetrics and Gynecology, discusses the results.
What contribution does this article make to the literature?
Ramirez: The LACC trial was an international, open-label, randomized non-inferiority trial that tested the hypothesis that minimally invasive radical hysterectomy is non-inferior to open radical hysterectomy in terms of disease-free survival (DFS) in patients with squamous cell carcinoma (FIGO 2009, stage IA1, with lymphovascular invasion) to IB1 (with squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix).
In particular, the aim of the study was to test the hypothesis that DFS after 4.5 years would be at most 7.2 percentage points worse in women who underwent minimally invasive radical hysterectomy than in women who underwent open surgery.
The study opened in 2008 with the aim of enrolling 740 patients and recruited patients from 33 centers in 24 countries. The LACC study was published in 2018 and was the first prospective, randomized trial to compare oncological outcomes between open and minimally invasive surgery in patients with early-stage cervical cancer who underwent radical hysterectomy.
The study showed that minimally invasive radical hysterectomy was associated with a four-fold worse DFS compared to the open procedure.
What are the highlights of the study?
Ramirez: A total of 631 patients were included in the study: 319 patients underwent minimally invasive surgery and 312 underwent open surgery. Of these, 289 patients (90.6%) underwent minimally invasive surgery and 274 (87.8%) underwent open surgery.
At 4.5 years, DFS was 85% in the minimally invasive group and 96% in the open group. Minimally invasive surgery was associated with a lower DFS rate than open surgery. The overall survival (OS) rate at 4.5 years was 90.6% versus 96.2% for the minimally invasive and open surgery groups, respectively.
Given the higher recurrence rate and poorer overall survival with minimally invasive surgery, an open approach is recommended as the standard of care. The LACC trial not only showed a lower survival rate in women who underwent minimally invasive surgery, but also found that the approach was not associated with a reduction in intra- or postoperative adverse events.
In addition, we conducted a prospective quality of life assessment for the first time, which showed that postoperative quality of life was similar in both treatment groups.
How do the results compare with other reports in the literature?
Ramirez: The results of this study differ significantly from those of previous literature. Up until the time of publication of the LACC study, the retrospective literature had shown that minimally invasive radical hysterectomy was associated with lower intraoperative blood loss rates, fewer postoperative complications, shorter hospital stay, and a faster return to normal daily activities.
Of particular note here is the fact that the majority of retrospective data focused on perioperative outcomes rather than oncological outcomes, and therefore not much emphasis was placed on investigating whether the minimally invasive approach was associated with worse oncological outcomes than the traditional open approach.
Many of the retrospective studies had major methodological limitations, including small sample size, use of historical controls, and lack of adjustment for confounders. These methodological deficiencies contributed to a biased assessment of the oncologic efficacy of minimally invasive surgery.
For which patients with early-stage cervical cancer would minimally invasive surgery be suitable?
Ramirez: This is currently one of the most discussed topics of discussion in the field of gynecological oncology. We are still debating the reason for our unexpected results. The most likely reason for the worse outcomes with minimally invasive radical hysterectomy is contamination of the abdominal and pelvic cavity by gross disease when using a uterine manipulator.
In addition, pneumoperitoneum can also play a role in the implantation of cancer cells throughout the peritoneum, as the tumor is manipulated during surgery.
Retrospective data have shown that by performing a vaginal protection maneuver (and thus avoiding tumor exit), it may be possible to achieve similar results to an open procedure while still retaining the advantages of minimally invasive surgery.
Based on current data, there appears to be a patient population considered low-risk who may benefit from minimally invasive surgery. This generally applies to patients with microscopic disease that has been resected and who have confirmed negative surgical margins. However, there are no prospective, randomized trials demonstrating that minimally invasive surgery is safe in this setting.
What is your most important message to practicing oncologists?
Ramirez: The most important message is to follow the recommendations of the National Comprehensive Cancer Network (NCCN) guidelines, which support the use of open surgery when performing radical hysterectomy for early-stage cervical cancer.
Patients in the early stages of the disease should only undergo minimally invasive surgery in clinical trials.
Read the study here and the expert commentary here.
Ramirez reported no disclosures.
