Two new studies revealed bad news about minimally invasive surgery for cervical cancer, a widely used procedure performed through small slits in the abdomen instead of a big incision.
Compared with the older, open abdominal operation, the minimally invasive approach was more likely to result in recurrence of the cancer and death, researchers found, in the first study that rigorously tested the two methods.
The results, published on Wednesday in The New England Journal of Medicine, had been circulating among cancer specialists in recent months and are already changing medical practices. Minimally invasive surgery for cervical cancer had been regarded as an advance that would help women: It lets patients recover faster, and since it had proved safe for other cancers, it was expected to be safe for cervical cancer, too.
“At M.D. Anderson, we have completely stopped performing minimally invasive surgery for cervical cancer,” said Dr. Pedro T. Ramirez, a leading expert in minimally invasive surgery for gynecologic cancers, and the lead author of one study. “Throughout the gynecologic oncology community, we’re seeing a transition back to the predominance of open surgery.”
But he also said that some surgeons, who had invested a lot of time, energy and money in learning the less invasive approach, did not want to give it up.
Dr. Ramirez and other researchers said the surprise findings show why it is essential to conduct clinical trials that test one treatment against another.
Surgery is not regulated the way drugs are. Although the Food and Drug Administration must approve new surgical devices, it does not control the way they are used. A tool approved for one purpose can be used for another. Surgeons can try new approaches, and innovations can catch on and spread, as long as hospitals allow it.
Some innovations have backfired. Morcellators, power tools that mince up tissue for extraction through small openings, were originally approved for orthopedic surgery and other procedures, but came into widespread use in operations to remove fibroids, a type of benign tumor, from the uterus.
But fibroids sometimes hide malignant tumors, and morcellation was found to spread cancer in some women, increasing their risk of death.
In that case, the F.D.A. did step in and recommend that the devices not be used “in the vast majority of women” undergoing fibroid surgery. Their use fell off sharply.
Morcellation is not used in surgery for cervical cancer. When minimally invasive surgery is performed, the uterus is removed intact through the vagina.
The study included 631 women and 33 hospitals in the United States, Colombia, Brazil, Peru, Italy, China, Australia and Mexico.
The results affect a relatively small number of women in the United States, where screening has reduced the incidence of cervical cancer to about 13,000 cases a year, with about 4,000 deaths. But worldwide, cervical cancer is the fourth most common malignancy and cause of cancer death in women, with 570,000 cases a year and 270,000 deaths.
The disease is caused in nearly all cases by the human papillomavirus, HPV, an extremely common, sexually transmitted virus. In most people, the immune system clears the virus and they never knew they were infected. But in some it persists, and can cause cervical cancer and other malignancies.
Dr. Ramirez said women with cervical cancer should discuss the types of surgery with their doctors, and should “question the approach of having minimally invasive surgery if that is what is suggested to them.”
Dr. Amanda N. Fader, director of the Kelly Gynecologic-Oncology Service at Johns Hopkins University, and the author of an editorial that accompanies the studies, said the results had “dealt a great blow” to the minimally invasive surgical method for cervical cancer. Johns Hopkins has also halted the procedure, reverting to open surgery “for the time being,” she said.
One question the findings raise is whether women who have already had minimally invasive surgery for cervical cancer have a higher risk of recurrence than previously thought. Dr. Ramirez said most recurrences happen within the first two years after surgery, so women who had the operation more than two years ago may have little to worry about.
For those who had the surgery more recently, doctors are still trying to determine whether extra follow-up is needed. In any case, doctors said, long-term survival rates after both types of surgery are still high.
Dr. Ginger Gardner, a gynecologic oncologist at Memorial Sloan Kettering Cancer Center in New York, said the studies were important, and her hospital was examining its own surgical results and discussing the findings with patients. She said decisions were being made on a case-by-case basis, and that the minimally invasive approach might still be appropriate for some women.
“This turns us on our heads a bit,” said Dr. Lee-may Chen, director of the gynecologic oncology division of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. “We thought laparoscopic surgery would be good for this patient population.”
She said that because of the findings, she now encourages most patients to have open surgery for cervical cancer. But she discusses the information with them, and would consider the minimally invasive approach for women who refuse open surgery, or for those who have a high risk of serious complications from open surgery.
Research had found that the minimally invasive approach, in use since around 2006, worked as well as open surgery to treat cancer of the uterus, which convinced many doctors that it would also be safe for cervical cancer.
But uterine cancer and cervical cancer are different diseases, and require different operations. Uterine cancer needs a simple hysterectomy, which means removing only the uterus.
Cervical cancer requires a radical hysterectomy, a more complex operation that takes out the uterus, part of the vagina and other surrounding tissues.
Dr. Ramirez and his team wanted to compare open and minimally invasive surgery, to find out if they were equally effective at eliminating cervical cancer. The research was paid for by M.D. Anderson and Medtronic, which makes instruments for minimally invasive surgery.
To ensure that all the surgeons were skilled in minimally invasive procedures, the team leaders required them to submit reports on at least 10 operations, and unedited videos of two.
Patients were recruited from June 2008 through June 2017, and were assigned at random to have either open or laparoscopic surgery, about half to each group. Their average age was 46, and all had early-stage cervical cancer (surgery is not used in advanced cases).
As the study progressed, it was monitored by an independent safety board that looked at the data to make sure patients were not being harmed. Partway through the project, the board saw too many deaths in the minimally invasive group. It recommended that the researchers temporarily stop adding new patients so the findings could be more closely examined.
A deeper analysis confirmed the higher death rate. The board said that no more patients should be enrolled, and that the hospitals should be told that minimally invasive surgery carried a higher risk of death. The original plan had been to include 740 patients, but the study stopped at 631.
After 4.5 years, 96.5 percent of the patients who had open surgery were free of cancer, as opposed to 86 percent in the minimally invasive group. At three years, 99 percent of the open-surgery patients were alive, compared with 93.8 percent of those who had minimally invasive operations.
With a median follow-up time of 2.5 years, 27 patients in the minimally invasive group had a cancer recurrence, compared with seven who had open surgery. There were 19 deaths in the minimally invasive group (14 from cancer), and three in the open group (two from cancer).
The researchers were stunned. Dr. Ramirez said they had expected to find that the two methods were equivalent.
Researchers do not know why there was a difference, but offer several theories. One is that an instrument passed through the cervix during some laparoscopic operations may inadvertently spread cancer cells. Another is that carbon dioxide, used to inflate the abdomen so that surgeons can see better during minimally invasive procedures, may help cancer cells invade tissue. Still another idea is that laparoscopic surgery may miss some cancerous tissue.
Dr. Fader said that if more research could explain the bad outcomes, it might become possible to identify patients for whom the minimally invasive approach would be safe.
A second study also found problems with minimally invasive surgery. It was not a clinical trial. Rather, it used information from databases to compare the results of the two surgical methods. It was paid for by the National Institutes of Health and charitable foundations.
In one analysis, 1,225 of 2,461 women had minimally invasive surgery, and the rest had open surgery. At four years, 9.1 percent in the minimally invasive group had died, compared with 5.3 percent who had open surgery.
Another analysis looked at the survival rate for cervical cancer surgery over time, and found that it began to decline when minimally invasive surgery was introduced, dropping by 0.8 percent a year after 2006.
“None of us expected this,” said, Dr. Jason D. Wright, an author of the study and the chief of gynecologic oncology at NewYork-Presbyterian/Columbia University Irving Medical Center. “We expected to find it was as safe.”
He said that because of the findings, most women at his hospital who need operations for cervical cancer are now having open surgery.
