SILVER SPRING, Maryland — On the first day of a 2-day meeting, a US Food and Drug Administration (FDA) advisory panel yesterday struggled to make sense of "very weak" data informing the risk from laparoscopic power morcellation (LPM) performed in women undergoing hysterectomy or myomectomy.
The FDA is seeking input from the Obstetrics and Gynecology Devices Advisory Committee on how to address the concern that when LPM is used to remove presumably benign fibroids during minimally invasive procedures, the morcellation process could inadvertently disseminate unsuspected malignant tissue, resulting in the "upstaging" of the tumor and worsening of the patient's prognosis.
Although the FDA and the manufacturers had previously been aware of that theoretical possibility, the risk was thought to be extremely low. The first instance of dissemination/upstaging after LPM was not reported to the agency until December 2013, with several other patient reports quickly following. In April 2014, the FDA issued an unusual letter calling for a halt to the use of LPMs until the data could be better analyzed.
The panel will not be voting on either day but, rather, answering a series of questions aimed at helping the FDA determine the magnitude of this potential risk to include in the product's revised labeling and assessing potential ways of mitigating that risk, such as the use of specimen bags.
At the same time, the panel is charged with weighing the risk of LPM against its intended advantages of allowing for more minimally invasive procedures, which are associated with reduced pain, shorter hospital stay, faster recovery, and reduced infection risk.
In public testimony, Hal C. Lawrence, III, MD, executive vice president and chief executive officer of the American College of Obstetricians and Gynecologists, Washington, DC, reiterated his society's May 2014 response to the FDA letter, calling for allowing morcellation to remain as a treatment option for women with fibroids.
"What we can do is work together to improve use of those procedures in the future, as we make complex, important treatment choices with our patients. I urge the committee today to recognize the importance of treatment options for all physicians, including ob-gyns," he said.
What Is the Risk?
Christopher M. Jones, PharmD, senior advisor in the FDA's Office of Policy and Planning, presented the agency's meta-analysis of 18 studies conducted from 1980 to 2011, suggesting that the risk for an unsuspected uterine sarcoma among women who undergo hysterectomy or myomectomy for presumed fibroids is 1 in 352. For leiomyosarcoma in particular, the most common of these tumors, the FDA's estimate is 1 in 498.
In 3 small case series of women who had such unsuspected malignancies, peritoneal dissemination of the tissue occurred with morcellation in 28% to 64% of the patients.
During public testimony, Elizabeth A. Pritts, MD, from the Wisconsin Fertility Institute, Middleton, presented her group's data from a much broader meta-analysis of 130 studies from1960 through May 2014. From the 67 prospective trials included, they derived an estimated occult leiomyosarcoma prevalence of 1 in 7450 women undergoing fibroid surgeries.
Panel members debated how to resolve that discrepancy, and to what degree it actually matters.
Keith B. Isaacson, MD, medical director of the Newton-Wellesley Hospital Center for Minimally Invasive Gynecologic Surgery, Newton, Massachusetts, said, "I certainly respect Dr. Jones' analysis, but I also respect the analysis by Pritts et al.... We need to find out which is the closest to being correct. I'd like FDA to review [Pritts'] paper, assuming it's published, and see if they're going to revise their numbers."
Carol L. Brown, MD, director, Office of Diversity Programs in Clinical Care, Research, and Training at Memorial Sloan Kettering Cancer Center, New York City, called the overall data "very weak" and said the most important missing piece for providing informed consent is the risk for up-staging of the tumor. What is needed, she said, is "to do is get more information from the women who this has happened to and their families."
However, Craig D. Shriver, MD, colonel, Medical Corps, US Army, professor of surgery, Uniformed Services University of Health Sciences, and chief, General Surgery Service, Walter Reed National Military Medical Center, Bethesda, Maryland, said that as a cancer surgeon, his perspective is, "if you see a lump, assume the worst, and treat it as if it's going to be the worst. If we knew the patient had a sarcoma, we wouldn't stick a device in and morcellate it."
He added, "To me, [the incidence and prevalence] doesn't matter. It's too much.... There are alternatives to power morcellation."
Dr. Shriver's remarks prompted applause from the many patient activists in the audience, including Boston, Massachusetts, anesthesiologist Amy Reed, MD, PhD, and her husband, Hooman Noorchashm, MD, PhD, a lecturer in surgery at Harvard Medical School and a cardiothoracic surgeon at Brigham and Women's Hospital. Amy Reed's case of tumor up-staging after LPM of presumed benign fibroids was the first such report to be filed with the FDA, and the couple's antimorcellation activism prompted reporting by other patients.
During the meeting, Dr. Noorchashm's shouting triggered a 5-minute halt to the proceedings and a reprimand from the panel's designated federal officer. Dr. Noorchashm is slated to give public comment on Friday, when the panel will address mitigation strategies to reduce the intraoperative risk during LPM and possible labeling changes for the devices.
FDA panel members are vetted for conflicts of interest and waivers granted if necessary. No waivers were granted for participants of this hearing. However, the Wall Street Journal reported that 1 panel member had stepped down before the meeting after FDA determined that he had accepted fees from a device manufacturer. Dr. Pritts and Dr. Lawrence have disclosed no relevant financial relationships.
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Cite this: FDA Panel Grapples With 'Weak' Data on Morcellation Risk - Medscape - Jul 11, 2014.