Minimally invasive surgery linked to increased recurrence and death in early-stage cervical cancer

Minimally invasive radical hysterectomy is associated with significantly higher risks of recurrence and death vs open surgery in early-stage cervical cancer, according to a recent meta-analysis that lends support to the findings of a controversial trial.

The meta-analysis included 15 high-quality observational studies with a total of 9,499 patients who underwent radical hysterectomy for early-stage (International Federation of Gynecology and Obstetrics 2009 stage IA1–IIA) cervical cancer. Results showed a 71 percent increase in the pooled hazard of recurrence or death (hazard ratio [HR], 1.71; 95 percent confidence interval [CI], 1.36 to 2.15; p<0.001) and a 56 percent increase in the risk of death (HR, 1.56; 95 percent CI, 1.16 to 2.11; p=0.004) among patients who underwent minimally invasive surgery (MIS) vs open surgery. [JAMA Oncol 2020, doi: 0.1001/jamaoncol.2020.1694]

According to the researchers, these findings, based on real-world data, were generally consistent with findings from the controversial LACC (Laparoscopic Approach to Cervical Cancer) trial, which showed an almost four-fold increased risk of recurrence and a 6.6-fold increased risk of death with minimally invasive vs open radical hysterectomy, leading to a decrease in the use of MIS for treatment of early-stage cervical cancer. [N Engl J Med 2018;379:1895-1904]

In the meta-analysis, 4,684 patients (49 percent) underwent MIS, and 2,675 of the MIS-treated patients (57 percent) received robot-assisted laparoscopy. MIS was predominantly performed by a robot-assisted approach (79–100 percent) in seven studies, while traditional laparoscopy predominated (85–100 percent) in the other eight studies.

No significant association was found between the prevalence of robot-assisted surgery and the magnitude of association between minimally invasive radical hysterectomy and risk of recurrence or death (2 percent increase in HR for each 10 percent increase in prevalence of robot-assisted surgery; 95 percent CI, -3.4 percent to 7.7 percent), or risk of all-cause mortality (3.7 percent increase in HR for each 10 percent increase in prevalence of robot-assisted surgery; 95 percent CI, -4.5 percent to 12.6 percent).

“Our results provide evidence to support the survival benefit associated with open radical hysterectomy for early-stage cervical cancer,” the researchers concluded. “Our finding of shorter overall and disease-free survival with MIS vs open surgery among women with early-stage cervical cancer provides real-world evidence that may aid patients and clinicians in shared decision-making.”

“The short-term advantages of MIS for gynaecologic cancers should be weighed against the risks of potentially worse long-term outcomes,” cautioned editorialists, citing the results of another recent study that showed an increased risk of capsule rupture with MIS for early-stage ovarian cancer. [JAMA Oncol 2020, doi: 10.1001/jamaoncol.2020.1617]

Over the 5-year study period (2010–2015), the rate of intraoperative malignant ovarian mass rupture increased from 20.2 percent to 23.9 percent, along with increased use of MIS (from 19.8 percent to 34.9 percent) documented during the same period. MIS with capsule rupture was independently associated with increased all-cause mortality vs MIS without capsule rupture (adjusted HR, 1.41; 95 percent CI, 1.01 to 1.97). [JAMA Oncol 2020, doi: 10.1001/jamaoncol.2020.1702]

“We have yet to identify factors that provide an explanation for the reported differences in oncological outcome between MIS and open radical hysterectomy in cervical cancer,” wrote the editorialists. “We owe it to patients to study any surgical or medical intervention adhering to the highest standards of clinical investigation. The two studies are another call to action.”