Studies Find Open Surgery Safer For Early Cervical Cancer

Researchers at the University of Texas MD Anderson Cancer Center and colleagues find that women who undergo minimally invasive radical hysterectomy to treat early-stage cervical cancer have worse outcomes than women who undergo abdominal “open” radical hysterectomy. Two studies found that minimally invasive surgery is linked with higher cervical cancer recurrence rates and worse overall survival. Study authors say the findings have already changed care at MD Anderson and could change care at other hospitals as well. The studies were published October 31, 2018 in the New England Journal of Medicine.

Most women with early-stage cervical cancer undergo a radical hysterectomy, which removes the uterus, cervix, and nearby tissues, as part of their treatment. Open surgery is done through a large incision in the abdomen and usually requires several days’ recovery in the hospital. Minimally invasive surgery is done through several small incisions using a camera and long instruments, sometimes using robotic arms that hold the medical tools. This type of surgery became more and more common during the past decade. By 2013, nearly 60% of radical hysterectomies were minimally invasive. The recovery time for minimally invasive radical hysterectomy is shorter, and patients usually go home the same day or the day after surgery.

Study 1: a randomized-controlled phase III clinical trial

The first study randomly assigned 631 women in 33 cancer centers in 13 countries with stage 1A or 1B cervical cancer to undergo minimally invasive surgery or open surgery. The trial was designed to compare disease-free survival at 4.5 years after surgery. That is the length of time after treatment ends that the patient shows no more signs or symptoms of cancer. Researchers had originally planned to include 740 women, but they stopped the study early when they learned women who underwent minimally invasive surgery had higher rates of recurrence, worse progression-free survival, and worse overall survival.

• The rate of disease-free survival at 4.5 years was 86% with minimally invasive surgery and 96.5% with open surgery.
• The 3-year rate of overall survival was 93.8% with minimally invasive surgery and 99% with open surgery.

“Until now, data focused primarily on surgical outcomes and the immediate period after, such as the recovery of the patient, length of stay, transfusion needs, and overall return to functional daily activities,” said study leader Pedro Ramirez, MD. “Our research is the first to prospectively compare the two surgical approaches and evaluate oncologic outcomes, including disease-free and overall survival and recurrence rates.”

Study 2: a retrospective, epidemiologic study

The second study analyzed data from two large cancer databases to compare survival rates between women with early-stage cervical cancer who underwent either of the two surgery types. Researchers looked at the National Cancer Database, which includes about 70% of newly diagnosed cancer cases in more than 1,500 US hospitals, and the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database, which provides information on cancer statistics. The study included 1,236 women who underwent open surgery and 1,225 women who underwent minimally invasive surgery.

This analysis also found that minimally invasive surgery was associated with worse overall survival than open surgery among patients with early-stage cervical cancer.

• Over a 45-month median follow-up, the 4-year mortality was 9.1% among women who had minimally invasive surgery compared to 5.3% for open surgery.
• Adoption of minimally invasive surgery coincided with the beginning of a decline in 4 -year relative survival rates of 0.8% per year between 2006 and 2010 in this population.

"Our research also found that compared with open surgery, minimally invasive surgery increased the risk of death among women who underwent radical hysterectomy for early-stage cervical cancer," said study leader J. Alejandro Rauh-Hain, MD. "Given these two studies, we believe that we can no longer recommend minimally invasive radical hysterectomies for our patients with early-stage cervical cancer."

Rauh-Hain said the study did not explain why minimally invasive surgery was linked with worse survival. He said more studies are needed to understand the cause of the survival differences.

About the results

In an accompanying editorial Amanda N. Fader, MD, from Johns Hopkins School of Medicine suggests that until further details are known “...surgeons should proceed cautiously, counsel their patients regarding these collective study results, and assess each woman’s individual risks and benefits with respect to minimally invasive as compared with open radical hysterectomy.” Fader calls the results surprising and alarming. She writes,” A partial explanation of why these results are so striking is that previous studies have focused overwhelmingly on surgical, rather than clinical outcomes.”

However, Fader says some women may still benefit from minimally invasive surgery. She notes that no patients with stage IA2 disease and only one with stage IB1, grade 1 disease had a recurrence in the clinical trial. In addition, women with a tumor size of less than 2 cm did not have worse outcomes with minimally invasive surgery than open surgery in either study.