Analyses Emphasize Caution in Use of MIS for Gyn Cancers

Minimally invasive surgery (MIS) for gynecologic cancers led to an increased risk of disease recurrence and death, according to two meta-analyses.

Review of 9,500 women who underwent radical hysterectomy for early-stage cervical cancer showed a 71% increase in the risk of recurrence and a 56% increase in the mortality hazard with MIS versus open surgery. A study of almost 9,000 women with early-stage ovarian cancer showed a statistically significant increase in the frequency of capsule rupture and adverse effect on survival that paralleled increased use of MIS over a 5-year period.

The hysterectomy findings supported those of a recent randomized trial that “unexpectedly” showed an increased risk of recurrence and mortality after MIS for hysterectomy. Collectively, the data amount to a “call to action” to explain the counterintuitive results, according to authors of an editorial that accompanied the two studies published in JAMA Oncology.

“We owe it to patients to study any surgical or medical intervention adhering to the highest standards for clinical investigation,” said Amer Karam, MD, and Oliver Dorigo, MD, PhD, of Stanford University in California. “The short-term advantages of MIS for gynecologic cancers should be weighed against the risks of potentially worse long-term outcomes.”

Early-stage cervical cancer treated with radical hysterectomy has a 5-year disease-free survival exceeding 90%. Until the early 1990s radical hysterectomy was performed almost exclusively by open laparotomy. Over the past 25 years, laparoscopic and robot-assisted minimally invasive hysterectomy gained widespread acceptance as standard of care for early stage cervical cancer, Alexander Melamed, MD, of Columbia University in New York City, and coauthors noted in the introduction to their study.

Randomized trials of minimally invasive versus open surgery for colon and endometrial cancer showed fewer complications and shorter recovery times for laparoscopic surgery with no difference in survival. The studies provided reassurance about the safety and efficacy of minimally invasive oncologic surgery. Until recently, no randomized trials had compared laparoscopic and open hysterectomy. Investigators in the Laparoscopic Approach to Cervical Cancer (LACC) trial sought to demonstrate the equivalence of laparoscopic and open hysterectomy but instead showed lower rates of disease-free and overall survival (DFS, OS) with minimally invasive approaches.

Two prior meta-analyses showed no difference in OS or DFS between minimally invasive and open hysterectomy. However, neither included several recent studies and both included studies that “are unquestionably biased” because of failure to control for confounders, Melamed and coauthors wrote.

To revisit the survival comparison between minimally invasive and open hysterectomy, investigators performed a systematic review and meta-analysis of relevant studies conducted through March 26, 2020. The analysis was limited to studies that controlled for confounding by tumor size or stage. Data analysis encompassed 15 observational studies and 9,499 patients, 49% of whom had minimally invasive procedures (robot-assisted in 57% of cases).

The pooled hazard ratio for disease recurrence or death was 71% higher among patients who had minimally invasive procedures (95% CI 1.36-2.15, P<0.001). A separate analysis of mortality produced a hazard ratio of 1.56 for minimally invasive versus open hysterectomy (95% CI 1.16-2.11, P=0.004). Use of robotics did not significantly affect the association between minimally invasive surgery and the hazard for recurrence or death.

The authors acknowledged that the analysis could not exclude the possibility of bias from residual confounding in the 15 studies, but they said such bias would likely lead to underestimation of the harms associated with minimally invasive hysterectomy.

“These results provide real-world evidence that may aid patients and clinicians engaged in shared decision making about surgery for early stage cervical cancer,” they concluded.

Derived from data in the National Cancer Database, the ovarian cancer study included women who underwent surgery for stage I epithelial ovarian cancer from 2010 to 2015. Investigators identified 8,850 patients, 2,600 (29.4%) of whom had minimally invasive procedures. The proportion of minimally invasive procedures increased from 19.8% in 2010 to 34.9% in 2015, almost an 80% increase (P<0.001).

Overall, capsule rupture occurred in 1,994 (22.5%) cases. The rate increased from 20.2% in 2010 to 23.9% in 2015, an 18.3% relative increase (P=0.02) during the period when use of MIS was increasing, Jason D. Wright, MD, also of Columbia University, and coauthors reported. By multivariable analysis, use of MIS was independently associated with capsule rupture (odds ratio 1.17, 95% CI 1.06-1.29).

Larger tumor size also was associated with an increased risk of capsule rupture. Women with capsule rupture were more likely to receive chemotherapy, regardless of whether they had unilateral or bilateral tumors (P<0.001)

Median follow-up for all patients was 39.4 months. The 4-year OS decreased from 2010 (91.0%) to 2015 (86.0%). Significantly fewer patients (P<0.001) remained alive at 4 years after capsule rupture whether they had open surgery (86.8% vs 90.5%) or MIS (88.9% vs 91.5%).

Wright and colleagues pointed out that the National Comprehensive Cancer Network recommends that MIS for early-stage ovarian cancer be limited to selected patients and experienced surgeons.

“Until more data become available, careful preoperative patient selection and intraoperative assessment prior to endoscopic oophorectomy should be performed to minimize the risk of tumor disruption and spillage,” they concluded.