Patients with early-stage cervical cancer who undergo open radical hysterectomy have significantly better outcomes than patients who undergo minimally invasive radical hysterectomy, according to a five-year study led by Houston Methodist Hospital researchers and published recently in the Journal of Clinical Oncology.

The study provides longer-term, more detailed evidence validating the landmark Laparoscopic Approaches to Cervical Cancer (LACC) trial, which resulted in the National Comprehensive Cancer Network changing its guidelines to recommend open surgery over laparoscopic radical hysterectomy. The paper on the trial was published in the New England Journal of Medicine in 2018.

"Minimally invasive procedures have great benefits when it comes to reducing perioperative complications and getting people back home and on their feet faster, but it's really important, especially when you're dealing with cancer, to confirm that the new version of the procedure has long-term outcomes that are at least as good if not better than the older version of the procedure it replaced," said Dr. Pedro T. Ramirez, first author on the research and chair of the Department of Obstetrics and Gynecology at Houston Methodist. "In the case of early-stage cervical cancer, the outcomes clearly aren't as good with minimally invasive surgery."

Dr. Ramirez added that the new study should reinforce the takeaway from the 2018 trial, whose transformative results he called difficult to overstate. Since the LACC study was published, he said he's "pretty much had to talk about it nonstop because no one — including those of us who designed and led the study — had any idea that the minimally invasive outcomes would be inferior, much less that they would be this inferior to the open approach."

Cervical cancer, most frequently diagnosed in women ages 35 to 44, is the fourth most common cancer in women globally. In the United States annually, about 11,500 new cases of invasive cervical cancer are diagnosed and about 4,000 women die of the disease, according to the CDC.

The new study follows all eligible trial participants to the prescribed four-and-a-half-year endpoint and analyzes disease-free survival, overall survival, tumor size and prior treatments in more detail.

It confirms the randomized controlled trial's initial findings that open surgery is the better standard of care, with higher overall survival and disease-free survival rates than minimally invasive surgery (MIS).

Upon final analysis, of the 631 patients enrolled (319 MIS; 312 open), overall survival was 96.2% for open surgery, compared to 90.6% for MIS. Disease-free survival was 96% for the open approach and 85% for MIS.

Enrolled participants were four times more likely to relapse and three times more likely to die following laparoscopic or robot-assisted minimally invasive techniques versus open radical hysterectomy.

Prior to the publication of the LACC trial, nearly 75 percent of all cervical cancer-associated radical hysterectomies were performed minimally invasively. Studies looking at minimally invasive versus open simple hysterectomy in endometrial cancer had shown that laparoscopic procedures were associated with lower rates of perioperative complications and equivalent oncologic outcomes at the five-year mark.

"We aren't entirely sure why minimally invasive surgery results are worse specifically for cervical cancer, but we have some good working theories," Dr. Ramirez said.

For one thing, endometrial cancer usually manifests as a very small tumor completely encased within the confines of the uterus, whereas cervical cancer is typically a larger exophytic tumor on the surface of the cervix, with potential exposure to the surgical field.

"It may have something to do with the gas used to expand the abdomen, the manipulators that allow for better exposure during minimally invasive surgery or the fact that you have to drag the cervix through the vaginal cavity for removal — all of these could increase the potential for tumor spillage and metastasis," Dr. Ramirez explained. "Multiple studies are underway to determine the precise cause and to see if there are better ways to perform minimally invasive procedures without these risks."

For now, however, best practice dictates that cervical cancer patients shouldn't undergo minimally invasive radical hysterectomies unless they are participating in an IRB-monitored clinical trial.

"It is important to continue to get the word out about the LACC trial's results, because there are still some providers who think the risks don't apply to them or their patients," Dr. Ramirez emphasized. "Unfortunately, I'm still seeing patients five years after the recommendations were changed who were told that minimally invasive surgery was the better choice, and now something that was curable has metastasized and all we can do is try to extend their survival."

The LACC trials were partially supported by Medtronic and philanthropic donations. Dr. Ramirez' collaborators include Kristy P. Robledo, Michael Frumovitz, Rene Pareja, Reitan Ribeiro, Aldo Lopez, Xiaojian Yan, David Isla, Renato Moretti, Marcus Bernardini, Val Gebski, Rebecca Asher, Vanessa Behan, Robert L. Coleman and Andreas Obermair.