Women with early-stage cervical cancer who underwent minimally invasive radical hysterectomy had higher rates of recurrence and worse survival outcomes than women who had open surgery, according to results of two studies published in The New England Journal of Medicine.
“Minimally invasive surgery was adopted as an alternative to open radical hysterectomy before high-quality evidence regarding its impact on survival was available,” J. Alejandro Rauh-Hain, MD, assistant professor in the department of gynecologic oncology and reproductive medicine and assistant professor in the department of health services research at The University of Texas MD Anderson, said in a press release. “[We] were surprised to find that, in our respective studies, surgical approach negatively affected oncologic outcomes for women with early-stage cervical cancer.”
About 13,000 women are diagnosed with cervical cancer each year in the U.S. Radical hysterectomy with pelvic lymphadenectomy remains the standard recommendation for women with early-stage disease.
Rauh-Hain and colleagues conducted a retrospective cohort study that included data on 2,461 women who underwent radical hysterectomy for stage IA2 or IB1 cervical cancer between 2010 and 2013. About half of the women (n = 1,225; 49.8%) had minimally invasive surgery.
Median follow-up was 45 months.
Propensity score-weighted analyses showed the risk for death within 4 years was 9.1% among women who had minimally invasive surgery and 5.3% among those who underwent open surgery (HR = 1.65; 95% CI, 1.22-2.22).
Between 2000 and 2006, prior to adoption of minimally invasive radical hysterectomy, the 4-year relative survival rate for women who underwent radical hysterectomy for cervical cancer remained stable, with an annual percentage change of 0.3% (95% CI, –0.1 to 0.6).
The adoption of minimally invasive surgery coincided with a decline in the 4-year survival rate of 0.8% (95% CI, 0.3-1.4) per year after 2006 (P for trend = 0.01).
Rauh-Hain and colleagues did not investigate why minimally invasive hysterectomy might be associated with shorter OS. However, researchers theorized that uterine manipulators — used to retract and visualize the pelvic area during the procedure — may spread microscopic tumor cells.
They also theorized that surgeons who performed the minimally invasive hysterectomies may have been more experienced with open surgery.
“The overall prognosis for women with early cervical cancer after minimally invasive or open hysterectomy is excellent,” study author Jason D. Wright, MD, associate professor of obstetrics and gynecology at Columbia University Vagelos College of Physicians and Surgeons and chief of gynecologic oncology at NewYork-Presbyterian/Columbia University Irving Medical Center, said in the release. “In either case, they should get periodic checkups and — if they experience any symptoms, such as pain or changes in vaginal bleeding — they should consult their gynecologic oncologist.”
In the other study, Pedro Ramirez, MD, professor of gynecologic oncology and reproductive medicine at The University of Texas MD Anderson Cancer Center, and colleagues sought to determine whether minimally invasive radical hysterectomy was equivalent to the open approach in terms of DFS.
The multicenter phase 3 trial included 631 women (mean age, 46 years) with early-stage cervical cancer (stage IB1, 91.9%).
Researchers randomly assigned 319 of the women to minimally invasive surgery (84.4% laparoscopy, 15.6% robot-assisted). The other 312 women underwent open surgery.
Minimally invasive surgery appeared associated with poorer DFS rates than open surgery at 3 years (91.2% vs. 97.1%; HR = 3.74; 95% CI, 1.63-8.58) and at 4.5 years (86% vs. 96.5%). This trend persisted after adjustment for age, BMI, disease stage, lymph node involvement and lymphovascular invasion.
Women who underwent minimally invasive surgery also were less likely to achieve 3-year OS (93.8% vs. 99%; HR = 6; 95% CI, 1.77-20.3).
Researchers stopped the study in 2017 due to the noted safety signal.
The researchers acknowledged study limitations given it did not reach its final intended enrollment.
“Our study reinforces the need for more randomized clinical trials in the field of surgery,” Ramirez said in a press release. “Too often, success of a new intervention in surgery is measured by retrospective data. We always need to test and measure our procedures to determine what is best for our patients.”
Ramirez also emphasized the need for more research to evaluate the effects of minimally invasive surgery in other scenarios where the approach is commonly used. – by John DeRosier
R eference s :
Melamed A, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1804923
Ramirez P, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1806395
Disclosure s : The authors report grants or other support from American Association of Obstetricians and Gynecologists Foundation, Foundation for Women’s Cancer, Jean Donovan Estate, Medtronic, National Institute of Child Health and Human Development, NCI, Phebe Novakovic Fund and a departmental research fund at The University of Texas MD Anderson Cancer Center. Wright reports consultant fees from Clovis Oncology and Tesaro. Ramirez and Rauh-Hain report no relevant financial disclosures. Please see the studies for all other authors’ relevant financial disclosures.