Better Survival After MIS for Advanced Ovarian Cancer

Debulking surgery is generally the next step after neoadjuvant chemotherapy for patients with advanced epithelial ovarian cancer, but there has been controversy as to whether women should undergo a minimally invasive laparoscopic/robotic procedure or open surgery.

A large review that used propensity score matching to account for confounders has weighed in the issue. The researchers found that patients who underwent minimally invasive surgery (MIS) had fewer complications and better survival in comparison with those who underwent open surgery.

The study was published in the May issue of Gynecologic Oncology.

“In the present large national database study examining surgical approach after NACT [neoadjuvant chemotherapy], MIS was not associated with worse overall survival compared with laparotomy. This finding was robust to potential unmeasured confounders and remained significant in sensitivity analyses after excluding those requiring surgical conversions from MIS to laparotomy, and those with clear cell, mucinous, or other histologies,” say investigators led by Kirsten Jorgensen, MD, an obstetrics/gynecology fellow at MD Anderson Cancer Center, Houston.

MIS is becoming more common for interval debulking surgery after NACT, but the trend is based mostly on case reports and small series, say the authors. The new findings help build the case for MIS and should give clinicians and patients “reasons to be optimistic,” they conclude.

Critics of the approach are concerned that abdominal exploration without the tactile feedback available with open surgery may result in some tumor being left behind. Although that may be a possibility, it “did not result in survival gains” in the laparotomy arm of the study, they say.

Promising Data

The study involved data on 7897 women who had stage IIIC or IV epithelial ovarian cancer that was diagnosed from 2013–2018. One quarter of these patients (n = 2021; 25.6%) underwent MIS after NACT; the rest underwent open surgery laparotomy.

During the 5 years of the study period, the use of MIS increased from 20.3% of all cases in 2013 to 29% in 2018.

Data were culled from the nationwide National Cancer Database.

Each MIS patient was matched with a patient who underwent open laparotomy. Patients were matched on the basis of age, year of diagnosis, race, facility type, comorbidity score, insurance, region, cancer stage, histology, household income, and other factors. Matching on year of diagnosis minimized confounding by advances in therapy that occurred during the study, such as the introduction of bevacizumab.

After propensity score matching, median overall survival was 46.7 months in the MIS group, vs 41 months in the laparotomy arm. The 5-year survival rate was 38.3% with MIS, vs 34.8% with laparotomy.

For the women who underwent MIS, hospital stays were shorter (median, 3 days vs 5 days), and they underwent fewer additional debulking procedures (59.3% vs 70.8%). In addition, they were less likely to have residual disease at the end of their procedure (23.9% vs 26.7%), which is possibly related to the loss of tactile feel with a closed procedure, the investigators say.

Among the women who underwent MIS, 30-day and 90-day mortality rates were better (0.3% and 1.4%, respectively) than the mortality rates for women who underwent laparotomy (0.7% and 2.5%, respectively).

All the findings were statistically significant.

Approached for comment, Kristina Butler, MD, a gynecologic oncologist at the Mayo Clinic in Phoenix, Arizona, said that the results are promising.

“Minimally invasive surgery at interval debulking shows opportunity in ovarian cancer treatment whereby women may have improved recovery, reduced morbidity, and improved quality of life while safely ensuring lengthy long-term survival,” she said.

However, the possibility that with MIS there is greater likelihood of leaving tumor behind is concerning. “Prospective study is needed to confirm” the outcomes with MIS, “given the lengthy history of standard-of-care surgery using laparotomy and clear correlation with survival and maximal tumor resection,” she said.

The gynecologic oncology community might not have to wait long for such data. The multicenter randomized LANCE Trial is pitting MIS against laparotomy for advanced ovarian cancer as well as other cancer types. The estimated completion date is May 2023.

The trial is being led by MD Anderson gynecologic oncologist Jose Alejandro Rauh-Hain, MD, who is also the senior author of the current study.

The Elephant in the Room

A key reason why prospective data are needed is that, as the investigators fully acknowledge, the women who underwent open procedures might have done so because they were sicker and had worse disease.

“In past studies, researchers may have selected the most favorable patients for MIS, such as those with better responses to chemotherapy based on pre-operative findings, those with better performance statuses, or those with fewer comorbidities, than patients who underwent laparotomy,” they say.

One of the limits of the study is that the reason why surgeons chose one approach over the other is unknown, as is the response to chemotherapy and even what regimens women were receiving.

However, with the rigorous propensity score matching, “the MIS group did not appear to be definitively more healthy and thus better surgical candidates than the laparotomy group based on available information, as the surgical approach did not differ based on disease stage, and older patients were more likely to undergo MIS than younger ones,” the investigators say.

Like Butler, the authors note that “the data presented here [are] promising”, but they also acknowledge that there are “additional limits of their study…[that] may limit interpretation.” For instance, the National Cancer Database does not capture progression-free survival, cancer-specific mortality, or long-term outcomes, they point out.

Results from the LANCE trial “may mitigate many of the limitations of this and prior retrospective studies,” they comment.

The study was funded by the National Institutes of Health and others. Jorgensen has disclosed no relevant financial relationships. Rauh-Hain has received consulting fees from the Schlesinger Group and Guidepoint. Another investigator is a former AstraZeneca advisor, and one served as an advisor to Avenge and Bio. Butler has disclosed no relevant financial relationships.

Gynecol Oncol. 2023 May;172:130-137. Abstract

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]

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