Previous research has shown that women with early-stage cervical cancer who undergo radical hysterectomy are usually cured, with some reports demonstrating 5-year disease-free survival rates that exceed 90%. “For years, radical hysterectomy was performed predominantly with an open abdominal approach,” explains Alexander Melamed, MD, MPH. “However, the advent of robot-assisted minimally invasive hysterectomy in the early 2000s led to widespread acceptance of these procedures as a standard treatment for early-stage cervical cancer.”

In 2018, the Laparoscopic Approach to Cervical Cancer (LACC) randomized control trial (RCT) unexpectedly found that minimally invasive hysterectomy was associated with a significantly higher risk of recurrence and death than open surgery. After the LACC study was published, the Society of Gynecologic Oncology encouraged surgeons to discuss these data with patients undergoing surgery for cervical cancer. The National Comprehensive Cancer Network also revised its guidelines to define open abdominal surgery as the standard recommended approach to radical hysterectomy.

“While RCTs like the LACC have unequaled internal validity and reduce biases, their generalizability may be limited by differences between the study participants and types of patients seen in routine clinical practice,” Dr. Melamed says. “Furthermore, minimally invasive hysterectomies are complex interventions and may differ between clinical trial and real-world settings.”

New Research

For a study published in JAMA Oncology, lead author Roni Nitecki, MD, Dr. Melamed, and colleagues conducted a systematic review and meta-analysis to appraise and synthesize high-quality real-world evidence comparing the risk of recurrence and death in patients with early-stage cervical cancer who underwent minimally invasive or open radical hysterectomy. “We conducted this study because prior meta-analyses found no differences in survival between these procedures but failed to include several more recent studies while also including results from analyses that were biased by not controlling for any confounders,” says Dr. Melamed, the senior author of the study.

The new meta-analysis included 15 observational studies from 2012 to 2020 that used survival analyses to compare outcomes after minimally invasive surgery and open radical hysterectomy in patients with early-stage cervical cancer. In total, the meta-analysis included 9,499 patients who underwent radical hysterectomy, with 4,684 undergoing minimally invasive surgery, 57% of which had robot-assisted laparoscopy.

In studies that reported confounder-adjusted survival analyses for disease-free survival, the pooled hazard of recurrence or death was 71% higher among patients who underwent minimally invasive radical hysterectomy than in those undergoing open surgery (Figure). The pooled hazard of all-cause mortality demonstrated that minimally invasive radical hysterectomy was associated with a 56% higher hazard of death compared with open surgery. “Based on our results, patients with early-stage cervical cancer fared worse with minimally invasive surgery than open radical hysterectomy,” Dr. Melamed says.

Assessing Implications

Findings from the new meta-analysis are important because they used high-quality, non-randomized cohort studies to compare minimally invasive surgery with open radical hysterectomy for early-stage cervical cancer. “These results provide real-world evidence that may help us in our efforts to engage patients in shared decision-making about surgery for early-stage cervical cancer,” says Dr. Melamed.

It has yet to be determined if minimally invasive radical hysterectomy might be appropriate for some patients with very small tumors. “There may be special circumstances where patients need a quicker recovery time, such as those who are caregivers for other people,” Dr. Melamed says. “The key is to have informed discussions on the risks and benefits with patients to ensure that a collaborative treatment decision is reached.”

Clinicians may benefit by reviewing results from the LACC trial because they were given a higher level of evidence than the current meta-analysis, according to Dr. Melamed. “Our study builds on what was seen in the LACC trial,” he says. “Our findings showed that the LACC trial data hold up in the real-world setting. Since there is potential harm associated with minimally invasive surgery for early-stage cervical cancer, it’s critically important for clinicians and patients to consider this factor when making treatment decisions.”

References

Nitecki R, Ramirez PT, Frumovitz M, et al. Survival after minimally invasive vs open radical hysterectomy for early-stage cervical cancer: a systematic review and meta-analysis. JAMA Oncol. 2020;6(7):1019-1027.Available at: https://jamanetwork.com/journals/jamaoncology/fullarticle/2766807.

Ramirez PT, Frumovitz M, Pareja R, et al. Minimally invasive versus abdominal radical hysterectomy for cervical cancer.  N Engl J Med. 2018;379(20):1895-1904.

Society of Gynecologic Oncology. Notice to SGO members: emerging data on the surgical approach for radical hysterectomy in the treatment of women with cervical cancer. Published November 13, 2018. Accessed September 30, 2020. Available at: https://www.sgo.org/clinical-practice/guidelines/notice-to-sgo-members-emerging-data-on-the-surgical-approach-for-radical-hysterectomy-in-the-treatment-of-women-with-cervical-cancer/.

National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: cervical cancer version 1. Accessed September 30, 2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cervical_blocks.pdf.