publication date: Dec. 15, 2017
As FDA, AHRQ spar over incidence estimates for uterine sarcomas, FDA reiterates recommendation to restrict power morcellation
By Matthew Bin Han Ong
About one in 225 to one in 580 women who undergo surgery for fibroids may have hidden uterine cancers, FDA concluded in a recent review of medical studies published over the past four years.
The updated estimate is generally consistent with one contained in the agency’s 2014 review, FDA officials said in a statement Dec. 14. Three years ago, the agency estimated that one in 350 women undergoing such surgery may have a previously undiagnosed sarcoma.
“Since the FDA first issued warnings about the risk of spreading unsuspected uterine cancer from the use of laparoscopic power morcellators, we have continued to review new research to ensure our recommendations reflect the most current scientific evidence,” Jeff Shuren, director of the FDA’s Center for Devices and Radiological Health, said in a statement. “Our latest analysis found a similar incidence of these hidden cancers to our estimate three years ago.”
FDA also estimates the rate of unsuspected, or “occult,” leiomyosarcoma, a particularly aggressive type of sarcoma, to be approximately one in 495 to one in 1,100.
This estimate “is in general agreement with our previous assessment of one in 498,” agency officials said. “Ranges in incidence represent estimates based on differing statistical analyses of available study data.”
FDA’s announcement is the latest milestone in the four-year controversy over power morcellation, a procedure that was performed on an estimated 50,000 to 100,000 women every year in the United States. This continued until a physician couple, Hooman Noorchashm and Amy Reed, turned the obscure “minimally invasive” procedure into a national public health debate (The Cancer Letter, July 4, 2014).
According to FDA, recent literature continues to suggest that women with occult cancers who received laparoscopic power morcellation have higher rates of cancer recurrence and worse outcomes, compared to women whose cancer was treated with manual morcellation or without any morcellation.
FDA said it acknowledges other organizations have different estimates, which are based on differing study methodologies and research questions.
“We recognize that some health organizations have reported a lower estimate of risk and that some groups continue to request that we scale back our recommendations,” Shuren said. “However, after looking at all the relevant data, we believe our estimates remain accurate, and our recommendation against the use of this device to remove fibroids in the vast majority of women is appropriate and critical to better protecting these women. We are committed to continuing to review new relevant data to assure patient safety.”
In 2014, the agency issued a guidance document that severely restricted the use of power morcellation. The document stated that morcellators should no longer be used for hysterectomies or fibroid removal in the vast majority of women getting these procedures.
The latest FDA announcement is a response to pressure from industry groups that are lobbying the agency to reverse its position on power morcellators, said Noorchashm, a cardiac surgeon and immunologist who, with his late wife Reed, led an aggressive campaign against the use of power morcellators.
“I suppose it’s a good thing that the agency did not cave in to the lobbying and that there are still elements left inside that agency capable of seeing the science and ethics of the issue with some degree of scientific and ethical clarity,” Noorchashm said to The Cancer Letter.
Reed, who was an anesthesiologist at Beth Israel Deaconess Medical Center when she underwent power morcellation at Brigham & Women’s Hospital in late 2013, died May 24 from complications stemming from disseminated leiomyosarcoma (The Cancer Letter, May 26).
The Cancer Letter’s four-year investigative series on the controversy surrounding power morcellation, “How Medical Devices Do Harm,” is posted here.
A separate review of data by the Agency for Healthcare Research and Quality—published on the same day as the FDA report—said the risk of unexpected leiomyosarcoma ranged from less than 1 to 13 of 10,000 surgeries.
This number, based on AHRQ’s review of 160 studies, skews closer to estimates commonly cited before power morcellation became a flashpoint in a polarizing debate on women’s health.
All medical procedures carry risk, and that risk can never be completely eliminated, said Hal Lawrence, executive vice president and CEO of the American College of Obstetricians and Gynecologists.
“With the recent release of two new reports from [FDA and AHRQ] on the management of uterine fibroids, ACOG is currently evaluating these evidence reviews to determine the need to update ACOG guidance on the medical and surgical management of leiomyomas,” Lawrence said to The Cancer Letter.
“As the leading organization representing health care providers for women, ACOG recognizes that minimally invasive surgery is an important option for some women undergoing surgery for uterine fibroids. Morcellation is a minimally invasive technique that spares women from increased morbidity and mortality associated with abdominal surgery.
“ACOG recommends that ob-gyns conduct a thorough patient evaluation, engage in shared decision making, and follow the informed consent process with each patient. Going forward, ACOG will continue to assess its position on the safe and effective use of power morcellation based on the latest scientific evidence and as more meaningful data is introduced.”
The continued attempts by the leadership of ACOG and the American Association of Gynecologic Laparoscopists to reverse FDA’s 2014 guidance on power morcellators is “despicable,” said Noorchashm, who was a cardiothoracic surgeon at Brigham & Women’s Hospital when Reed underwent the procedure.
“You can imagine why I’m furious; I held Amy in my arms until I couldn’t feel her pulse anymore,” Noorchashm said. “The fact that these so-called doctors are using as a defense of their despicable position, the notion that ‘cancer is a bad disease anyway’ and that these women are doomed anyway, is bankrupt and disgusting.
“There is only one explanation to the behavior exhibited by the leaderships of ACOG and AAGL: these are businessmen trying to retain and resurrect a technology that is central to their business model. This is not about saving lives or being safe. It’s about a lucrative and engineered business practice.
“Let me be clear, ACOG and AAGL leaders disgust me with their continued statements, lobbying and protectionism towards an avoidable technique that killed my wife—and many other unsuspecting women.”
Hooman Noorchashm and children at the grave of Amy Reed, his wife, whose leiomyosarcoma was upstaged by power morcellation. Reed died on May 24.
FDA chalked up the difference between its estimates and AHRQ’s estimates to methodology.
“In terms of the difference between AHRQ’s estimate and ours, as with any review of available scientific literature, the studies chosen to be included in an analysis can impact the results,” FDA officials said in a statement to The Cancer Letter. “In its analysis, the FDA chose to include only those studies that had the following characteristics:
“Had as a stated goal or research objective, evaluation for the presence of sarcoma. This can be an important issue as studies with other goals may have excluded women at higher risk for the disease (e.g. post-menopausal women) or fibroids of certain sizes; and,
“Included only women who had been diagnosed with presumed benign fibroid disease and not those with mixtures of patients including women without fibroids.
“The FDA and AHRQ used different methodologies, and this likely explains the differences in the estimated rates of occult or hidden uterine cancers. While the two agencies included many of the same studies, not all overlapped.”
The major difference between the FDA and AHRQ reports on uterine fibroid treatment is the set of included studies, AHRQ officials said.
“AHRQ included any study of hysterectomy or myomectomy for uterine fibroids that included histopathological, or study of tissue, analysis of samples,” AHRQ officials said in a statement to The Cancer Letter. “This led to a larger number of included studies, in particular studies with more premenopausal younger women.
“As both reports note, there is evidence that the prevalence of leiomyosarcoma increases with age, but not enough information is given in the studies to do a comprehensive analysis of the risk by age. The range of risk estimated by AHRQ and FDA overlap. AHRQ’s range is <1 to 13 out of 10,000. FDA’s range is 1 in 495 to 1 in 1,100 or 9 to 20 out of 10,000. Better data to determine age-based risk are needed to help patients make decisions about treatments.”
The AHRQ report on the management of uterine fibroids is significantly flawed, said Michael Paasche-Orlow, a professor of medicine at Boston University School of Medicine.
“Part of the problem has to do with the fact that the evidence summary was framed too narrowly,” Paasche-Orlow said to The Cancer Letter. “They have focused their evaluation of the harms of morcellation on the unexpected presence of leiomyosarcoma. This is a good place to start, as LMS is an extremely bad kind of cancer, but this is a wildly inappropriate framing.
“If you spread any cancer or even precancerous cells in a woman’s body by chopping up what you inaccurately presumed was benign tissue—you have done her no favor! Indeed, you may have mortally harmed this person. The framing of this report is so narrow that it appears almost like a conscious effort to minimize the risks morcellation poses to women.
“Another major problem with this report is that they have used a method of data collection for their metanalysis that severely distorts the issue of the prevalence of LMS. A large portion of the data they have included in their prevalence estimates come from clinical trials in which the follow up observation period is severely limited.
“This systematically underestimates the spread of cancer in these women. Similarly, a lot of the studies they have included are for patients undergoing selective myomectomy. For several reasons, this will also yield a very distorted prevalence estimate with a very strong bias toward underestimating the problem. What would motivate them to do such a thing?”
In addition to its review of recent literature, FDA published a white paper that provides an update on medical device reports the FDA received through April 2017 related to the use of power morcellators and how hysterectomy and myomectomy procedure selection has changed since the FDA’s 2014 warning against the routine use of morcellators to treat suspected uterine fibroids.
This data demonstrates that overall, use of laparoscopic power morcellators has decreased since the FDA warned about it in 2014.
“Two reports showed a large decrease in the use of LPMs,” agency officials wrote in the white paper. “However, it also appears that minimally invasive surgical techniques remain a common procedure. Data from the Sentinel System also showed a reduction in the use of LPMs and suggest a ‘flattening’ of the rates for laparoscopic procedures (which had been increasing) and open procedures (which had been decreasing). Despite changes in routes of surgery, data on rates of complications also varied, with several noting no significant changes in perioperative complications.”
Percentage of Hysterectomy Procedures performed laparoscopically
The agency’s recommendations for patients and health care providers remain unchanged (The Cancer Letter, Dec. 5, 2014).
“The FDA continues to monitor and evaluate the risks and benefits of laparoscopic power morcellation,” officials said in a statement. “The FDA continues to believe the use of power morcellators to remove uterine fibroids should be limited to a small number of women, typically young women who wish to bear children and otherwise could not without use of a morcellator, and who choose this option after being informed of the risks.”