Unexpected outcome in hysterectomy study

Women undergoing radical hysterectomy for early cervical cancer had a significantly higher risk of disease recurrence and worse long-term survival with minimally invasive surgery (MIS), including robotic-assisted procedures, two separate studies showed.

The number of disease recurrences after laparoscopic or robotic-assisted procedures was almost four times higher than the number of recurrences after open surgery, although the absolute numbers were small: 27 recurrences versus seven in more than 600 patients. The difference translated into a hazard ratio for disease-free survival (DFS) of 3.74 (at 4.5 years) for MIS versus open surgery.

Significantly more patients who had conservative surgery died during a median follow-up of 2.5 years: 19 versus three with open surgery. Although the absolute numbers remained small, the difference meant that women who had MIS were six times as likely to die during the follow-up period, Pedro T. Ramirez, MD, of the University of Texas MD Anderson Cancer Center in Houston, reported here at the Society of Gynecologic Oncology annual meeting.

"Disease-free survival at 4.5 years for minimally invasive radical hysterectomy was inferior compared to the open approach," Ramirez said in conclusion. "Minimally invasive radical hysterectomy was associated with higher rates of locoregional recurrence. Results of [this] trial should be discussed with patients scheduled to undergo radical hysterectomy."

A second study reported at the meeting yielded a similarly unexpected result: almost a 50% higher risk of dying within 4 years of surgery with minimally invasive hysterectomy compared with open surgery. The retrospective analysis, based on two national databases, revealed a statistically significant trend toward declining survival as adoption of MIS increased, said J. Alejandro Rauh-Hain, MD, also of MD Anderson.

Cautious Assessment

Having had 2 weeks to review the two studies, the study's discussant, Shitanshu Uppal, MD, IHPI member of the University of Michigan in Ann Arbor, said he had already progressed through the "five stages of grief" in reaction to the unexpected results: "I've gone through denial and anger. I couldn't bargain, and depression wasn't an option, so I think I'm getting to the acceptance thing."

Uppal said he did not dispute the data and agreed with Martinez' conclusion that the results must be discussed with patients. However, he noted several limitations of the international phase III Laparoscopic Approach to Cervical Cancer (LACC) trial. Because of slow patient enrollment, the trial ended in a futility analysis of 631 patients, instead of the planned 740. A fair amount of key histopathologic data remained unknown, including tumor size in a third of cases. The minimally invasive arm tilted heavily toward traditional laparoscopic surgery as opposed to robotic-assisted (84% versus 16%).

With regard to the retrospective analysis, Uppal encouraged continued monitoring of survival data for the more recent years of the study period, looking for potential alternative explanations for the declining survival and to confirm the association with MIS.

He also presented data in response to his rhetorical question: "What will happen if we abandoned minimally invasive surgery?" Referring to the National Inpatient Sample for 2015, he noted that a return to open surgery for all patients would result in 85 additional complications, 70 transfusions, and approximately two deaths per 1,000 cases per year. Another recent analysis of uptake of minimally invasive hysterectomy suggested that an additional six lives per 1,000 cases per year would be saved by increased uptake versus open surgery.

Using the lower estimate for deaths would result in 2.60 lives saved per 1,000 cases with open surgery versus a net loss of 1.25 lives with the higher estimate, as LACC data suggested 4.75 lives would be saved per 1,000 cases if minimally invasive surgery were abandoned.