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VIDEO: Cervical cancer laparotomy outperforms minimally invasive surgery

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Further research needs to explain the findings

The findings from these studies appear valid and should be discussed with patients.

The findings raise a major question: Why has minimally invasive surgery (MIS) led to worse survival rates than laparotomy? Several possible explanations can be hypothesized: The uterine manipulator used in MIS led to local spread of cancer cells; MIS involves a learning curve and initial attempts at MIS did not remove enough of the tumor; and MIS led to increased exposure of the peritoneal cavity to the cancer. The findings also raise another question: Why has MIS for cervical cancer performed less well than MIS for cancers from other organs, such as endometrial and prostate?

Mitchel L. Zoler/MDedge News

Dr. Shitanshu Uppal

We also need to place these findings in context. Radical hysterectomy using MIS has shown clear advantages over laparotomy in terms of complications and blood loss. I analyzed data from the U.S. National Inpatient Sample for 2015, and I calculated that, for every 1,000 patients treated for early-stage cervical cancer by MIS radical hysterectomy, compared with laparotomy, the MIS approach would produce 70 fewer blood transfusions, 55 fewer medical complications, 35 fewer infectious complications, six fewer surgical complications, and two fewer deaths during the same hospitalization.

The overall survival results from the LACC trial calculate out to 4.75 added deaths per year for every 1,000 patients treated with MIS, compared with laparoscopy. But the National Inpatient Sample data suggest that MIS cuts mortality by about two deaths per year per 1,000 patients, compared with laparotomy, and mortality data from a different analysis (Gynecol Oncol. 2012 Oct;127[1]:11-7) suggest that MIS might prevent six deaths annually for every 1,000 patients, compared with laparotomy. Overall, these three sets of findings suggest roughly comparable mortality outcomes from MIS and laparotomy, but with MIS having the bonus of fewer complications and less need for transfusions.

The cautions and concerns raised by the LACC trial and Dr. Rauh-Hain’s analysis of observational data cannot be easily dismissed. We need to figure out why the results from both studies show worse survival and recurrence rates with MIS, and we need to identify whether subgroups of patients exist who might clearly benefit from either the MIS or open-surgery approach.

Shitanshu Uppal, MD , is a gynecologic oncologist at the University of Michigan in Ann Arbor. He made these comments as designated discussant for the two studies. He had no disclosures.


 

REPORTING FROM SGO 2018

– Use of minimally invasive radical hysterectomy to treat early-stage cervical cancer has grown over the past decade, and in current U.S. practice, roughly half of these cases are done with a minimally-invasive approach, with the rest done by conventional laparotomy. But the first data ever reported from a large, prospective trial that compared the efficacy of both methods for cervical cancer had the unexpected finding that disease-free survival following minimally invasive procedures significantly lagged behind radical hysterectomies done by open laparotomy, Pedro T. Ramirez, MD, said at the annual meeting of the Society of Gynecologic Oncology.

Just after this report came results from a second study that used propensity score–adjusted observational data from the National Cancer Database and found significantly worse overall survival following minimally invasive radical hysterectomy for early-stage cervical cancer, compared with laparotomy, said J. Alejandro Rauh-Hain, MD, a gynecologic oncologist at the University of Texas MD Anderson Cancer Center in Houston.


Both findings were “very surprising,” said Dr. Rauh-Hain in a video interview. “I was pretty sure we’d see no difference” in outcomes between minimally invasive radical hysterectomies and the same surgery either done by laparoscope or robotically assisted.

Prior prospective comparisons of minimally invasive and open surgical methods for other cancer types, including endometrial, gastric, and ovarian, showed no differences in cancer recurrences and survival, which led to widening use of minimally invasive surgery (MIS) for cervical cancer despite no direct evidence supporting equivalence, Dr. Rauh-Hain noted. “We adopted it with no data. It made sense that cervical cancer would be the same as endometrial cancer,” he explained.

The Laparoscopic Approach to Cervical Cancer (LACC) trial ran at 33 centers in 12 countries, including six U.S. centers. The study randomized women during 2008-2017 who had stage 1A1, 1A2, or 1B1 cervical cancer to either MIS or open surgery for a radical hysterectomy. Each participating center had to submit to a trial review committee full case records for 10 patients and unedited surgical videos of two patients who had previously undergone a minimally invasive radical hysterectomy at the center to document local prowess with MIS.

Dr. Ramirez and his colleagues designed LACC to prove the noninferiority of MIS and calculated an expected enrollment of 740 patients based on statistical expectations, but the study stopped early after enrolling 631 patients because of the adverse outcomes identified in the MIS patients, with a median follow-up of 2.5 years instead of the planned follow-up of 4.5 years. The study reached the 4.5-year follow-up in about 39% of patients. Of the 312 patients randomized to undergo laparotomy, 88% actually underwent the surgery; of the 319 patients randomized to MIS, 91% received this surgery, with 16% of the MIS procedures done using robotic assistance.

The study’s primary endpoint was disease-free survival at 4.5 years, which occurred in 86% of the MIS patients and in 96.5% of the laparotomy patients, a difference that failed to meet the study’s prespecified definition of noninferiority for MIS, reported Dr. Ramirez, a professor of gynecologic oncology and director of Minimally Invasive Surgery Research and Education at the MD Anderson Cancer Center. In addition, several secondary analyses of the data all showed starkly superior outcomes in the laparotomy subgroup.

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