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More Bad News for MIS in Cervical Cancer

CHICAGO — Minimally invasive hysterectomy conferred a significantly higher risk of cervical cancer recurrence compared with abdominal procedures, data from eight high-volume centers showed.

An unadjusted analysis showed the hazard for 5-year recurrence-free survival (RFS) more than doubled with minimally invasive surgery (MIS). Two different adjusted analyses showed even larger disparities, yielding hazard ratios (HRs) of 4.16 and 3.71, according to Shitanshu Uppal, MD, of the University of Michigan in Ann Arbor.

A propensity-matched analysis showed almost a three-fold increased risk of recurrence with MIS, he reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The report continued a run of bad news for MIS hysterectomy that began in 2018 at the Society of Gynecologic Oncology (SGO) meeting, when one study showed an increased risk of recurrence with MIS, and another showed an increased mortality risk. Just last month, an analysis by the British public health service showed a fourfold spike in the survival hazard for patients who underwent MIS hysterectomy from 2013 to 2016.

“Is this a fight worth fighting?” Uppal asked. “Whether minimally invasive hysterectomy should continue or not is up for debate. If we do so, there will be some big questions on cervical cancer volume. Are we ready for centralization of care?”

“Another issue is that patients who have open surgery, and then enhanced recovery protocols, have minimal morbidity. The benefit derived from minimally invasive techniques might not be worth the risk involved,” he stated.

‘Belief Bias?’

The sudden influx of negative reports might have triggered a “belief bias” reaction among supporters of MIS hysterectomy, suggested ASCO invited discussant Patricia Eifel, MD, of the MD Anderson Cancer Center in Houston. She noted that MIS for cervical cancer had rapid adoption and uptake as a worldwide standard, supported by a number of positive, albeit retrospective, reviews of data.

For example, an analysis of 23 studies involving 4,205 patients showed advantages for MIS related to operative time, blood loss, hospital stay, return of normal bowel activity, transfusions, and bladder catheterization. The benefits led the authors to conclude that laparoscopic radical hysterectomy outweighs abdominal radical hysterectomy “in most essential aspects.”

“[The spate of negative studies] was a shock to many surgeons. Many, many editorials were published. Efforts to explain this away and to find ways to rationalize how it might not be a knock-out punch for minimally invasive surgery,” said Eifel.

“I guess [Uppal’s report] is just an additional bit of evidence for belief bias: The drive to accept believable conclusions in the face of inconclusive results is very strong,” she added. “Even well-substantiated conclusions may be difficult to accept if they counter belief. I think we need to look very closely at data that follows our preconceived notions to determine whether we really are accepting it because of the validity and the quality of the data, or because we want it to be true.”

As the invited discussant for the SGO presentations, Uppal expressed surprise at the negative data regarding MIS. He reported findings at ASCO from an analysis that attempted to address some of the perceived shortcomings of the negative studies. Though retrospective, the data came from eight, high-volume academic centers with reputations and recognition for quality care.

Key Findings

The analysis involved 731 patients who underwent radical hysterectomy for cervical cancer from Jan. 1, 2010 through Dec. 31, 2017. Patients with preoperatively identified metastatic disease were excluded. MIS was performed in 72.1% of the cases, and 91% of the MIS cases involved robotic assistance. Eight of the 204 open abdominal procedures were converted from MIS.

Baseline characteristics had several imbalances: Fewer black patients and more Hispanic patients had open surgery; missing data on preoperative tumor size for 15.6% of the MIS group versus none of the open-surgery group; missing data on tumor grade for 13.7% of the MIS group versus 4.9% of the open group; the open-surgery patients had larger tumors at final analysis (2 vs 1.3 cm); median follow-up of 45 months for the open-surgery group versus 30.5 months for the MIS group; and missing data on lymphovascular space invasion (LVSI) for 4.2% of MIS patients versus 0.5% of the open-surgery group.

The primary outcome of the study was a 5-year recurrence rate, which was 6.9% with open surgery and 9.3% with MIS. An unadjusted analysis of RFS yielded an HR of 2.06 for the MIS group (95% CI 1.06-4.00). Investigators performed two adjusted analyses. In both analyses they controlled for comorbidities, race, body mass index, pathology grade, histology, surgical approach, adjuvant therapy, and LVSI. One analysis controlled for preoperative tumor size and the other for final tumor size.

The two analyses yielded HRs of 4.16 with inclusion of preoperative tumor size and 3.71 when tumor size on final pathology was incorporated.

From the total study population, Uppal and colleagues formed propensity-matched cohorts involving 132 patients who had abdominal surgery and 125 who had MIS. The 5-year recurrence rate was more than two times higher in the MIS group (14.4% vs 6.1%, P=0.027), which translated into an HR of 2.93. Overall survival was not significantly different between groups.

One additional analysis suggested that use of a uterine manipulator might be a contributing factor to the higher recurrence rate seen in MIS cases, said Uppal. In 31 cases performed without a manipulator, none of the patients had disease recurrence. In contrast, recurrence rates of 8.2% and 11.7% were seen with the use of intrauterine and vaginal manipulators, respectively.

Uppal disclosed no relevant relationships with industry.


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