publication date: Jul. 25, 2014

Families harmed by power morcellation pose on FDA’s White Oak campus July 11, following a two-day hearing on the controversial surgical procedure


There was no formal consensus on either an outright ban on power morcellators or issuance of a “black box” warning label.

“Multiple individuals mentioned the desire to avoid any kind of morcellation of tissues, and to remove the specimens intact,” said Michael Diamond, chair of the FDA Obstetrics and Gynecology Devices Advisory Committee, summarizing the panel members’ responses to one of the questions.

No vote was taken. The panel’s wide-ranging discussion and restrained wording of the consensus agreement give the agency considerable leeway to determine the next course of action.

A black box label is the FDA’s sternest warning, indicating that the device has serious possible risks.

Power morcellation is performed on an estimated 100,000 women in the U.S. a year with a minimally invasive device that pulverizes a patient’s uterus or fibroids into fragments, for easy removal through a small incision.

The problems occur when power morcellators disseminate cells from undetected cancers. The technique became the subject of public discussion over the past year, after a morcellator spread leiomyosarcoma during surgery performed on Amy Reed, a Harvard physician.

Reed’s husband, Hooman Noorchashm, a cardiothoracic surgeon at Brigham & Women’s Hospital, launched a national campaign against power morcellation, drawing together other patients who were similarly harmed (The Cancer Letter, July 3).

The FDA issued an advisory April 17 discouraging the use of power morcellation, stating that one in 350 women who undergo hysterectomy or myomectomy for fibroids have an unsuspected uterine sarcoma.

The publicity and pressure culminated in the advisory panel’s hearing July 10 and 11.

The agency’s effort to get advice didn’t go smoothly. Days before the hearing, The Wall Street Journal reported that three panel members had received consulting fees from Ethicon, the Johnson & Johnson subsidiary that manufactures laparoscopic power morcellators.

Andrew Brill, a San Francisco gynecologist, stepped down two days before the hearing after an FDA review found that he had received nearly $100,000 in consulting fees in 2013 from Ethicon. The other two panel members—Keith Isaacson, a Newton-Wellesley Hospital gynecologist, and panel chair Michael Diamond, remained on the panel.

The panel’s debate on power morcellators was extensive, ranging from dramatically disparate risk estimates, to cancer detection and mitigation strategies, and from alternative procedures to containment systems.

Several panel members discouraged the use of power morcellation, citing the lack of reliable uterine cancer detection methods, and advocated a return to making larger incisions and other treatment options.

Colleen Gallagher, a bioethicist and associate professor at MD Anderson Cancer Center, said that power morcellators can cause real—but avoidable—harm.

“We rarely hear about the principle of non-maleficence being so important,” said Gallagher, a panel member and chief and executive director of the MD Anderson Section of Integrated Ethics in Cancer Care. “And non-maleficence is the principle out of which the ‘do no harm’ comes from. I think for this particular question, that principle of non-maleficence, meaning we want to avoid harm to the very best of our ability—it’s really not necessarily avoidable all the time, it’s not a zero sum—combined with the principle of justice, specifically that of what the society owes to one, is why the FDA is doing what it is doing.

“As an ethicist, I don’t believe at this moment that morcellation—for the purposes that we’re talking about today, not for other things, but for this particular thing—is something that I would support.”

 


“Shame on You…”

At the public hearing session, Noorchashm and other patient advocates called for an outright banning of the device.

“Shame on you,” Noorchashm said at the hearing, aiming his comments at those who were defending power morcellation. “Ban this now. People’s lives are in your hands.”

Representatives of gynecologic professional societies disagreed. “Let us improve, but not abandon power morcellation,” Jubilee Brown, a spokesperson and member of the board of trustees of the American Association of Gynecologic Laparoscopists, said to the panel. “Our obligation is not only for patients with leiomyosarcoma. It is to all of our patients.”

Brown added that if power morcellation were to be eliminated, 17 more women could be expected to die per year because conventional surgery is more invasive. “We must not sacrifice our patients in an emotional response to a rare event,” Brown said.

Most panel members stopped short of recommending a ban. One exception was Craig Shriver, the founding director of the John P. Murtha Cancer Center at Walter Reed National Military Center.

“As a surgical oncologist trained in the core, basic Halstedian principles of cancer surgery, I’m always myself asking, and adhering to and teaching others to adhere to the tenet of treating all masses as cancer until proven otherwise, which is born out of the ancient Hippocratic principle of patient care and first, do no harm,” Shriver said at the hearing July 11.

“I’ve been perplexed over the last two decades, watching the introduction of a laparoscopic power morcellation technique that is totally anathema to these and my core principles as a cancer surgeon.

“After these two days of testimony and data, based on science, I have only more strongly reaffirmed my commitment and belief that there is, at present, no safe way to offer laparoscopic power morcellation as a part of any minimally invasive surgery.

“I conclude and state as a member of this advisory committee to the FDA that my position is that the device under consideration, the power morcellator, should have its Class II device status immediately withdrawn, and its use in any laparoscopic surgery banned.

“Going forward, I answer the FDA questions to the panel only in the context of what a future submission to the FDA for any new technology related to this approach under a submission as a Class III device with relevant preclinical testing, and in the context of properly constituted and informed patient clinical trials, prior to any future approach in this field.”


JAMA Paper Consistent with FDA Analysis

New research, published July 22 in the Journal of the American Medical Association, reinforces the FDA estimate. Doctors at Columbia University found that 1 in 368 women undergoing hysterectomies have an undetected uterine cancer that could be spread by a power morcellator’s spinning blades.

The study looked at 36,470 women who underwent power morcellation from 2006 to 2012 and found that 99 of those women had uterine cancer that was unidentified at the time of the procedure.

“Although morcellators have been in use since 1993, few studies have described the prevalence of unexpected pathology at the time of hysterectomy,” the authors wrote. “Prevalence information is the first step in determining the risk of spreading cancer with morcellation. Patients considering morcellation should be adequately counseled about the prevalence of cancerous and precancerous conditions prior to undergoing the procedure.”

At the FDA hearing, panel member Shriver said that there is no reliable method of detecting a uterine sarcoma.

“There are no tests that I’ve been shown on the data or the science that, either in isolation or together, are good enough—good enough at this time—or in the near-term future, that determine the presence of an unsuspected sarcoma in a woman with presumed uterine fibroids,” Shriver said. “Even in the best studies, the level of evidence of that uncontrolled—of those data—is uncontrolled longitudinal studies, which are low-level evidence.”

 


Containment Bags?

The safest way to perform a hysterectomy or myomectomy would be to remove the specimen intact, several panel members said.

“The vaginal route is the favorite route for many reasons because it is the least invasive, it is associated with the lowest risk of injury, less amount of pain, and you can remove a specimen—without morcellation—through the vagina,” said Cheryl Iglesia, section director of Female Pelvic Medicine and Reconstructive Surgery at MedStar Washington Hospital Center in Washington. “To the degree that it can be done vaginally without morcellation, which is my preferred route, and it is done in 25 percent of hysterectomies in the U.S., we need additional training to make sure that technique stays and that we have the special skills to use it. I have a very strong opinion about the route through the vagina.”

The vaginal route would also preclude the need for a containment system, said Carol Brown, director of the Office of Diversity Programs in Clinical Care, Research, and Training at Memorial Sloan Kettering Cancer Center.

“We have evidence from the specialty of gynecologic cancer and gynecologic oncology that you do not need to put a known cancer specimen in a bag,” Brown said. “The vast majority of known endometrial cancers including uterine carcinosarcomas, including known leiomyosarcoma, at my institution and my practice, if the patient meets the other criteria, we do choose minimally invasive because it is better for that patients in terms of significant outcomes, and we remove the specimen through the vagina. I do think that, again, the best thing to do is to not chop cancer up, no matter how you chop it up.

“We know that you can take uteruses out through the vagina without a bag even if they have cancer in them, as long as they are intact. But I would focus on a technique of, again, avoiding any type of morcellation when you’re doing a hysterectomy, or removing a fibroid, and the best potential orifice to get that out is going to be the vagina.”

Panel chair Diamond, professor and chair of the Department of Obstetrics and Gynecology and associate dean for research at Georgia Regents University, said in a summary of the consensus:

“First of all, there are some techniques such as vaginal surgery, when it’s possible, for the removal of an intact uterus—that would be a mitigation strategy that could be utilized. There is also concern with supracervical hysterectomy, and potentially cutting across a tumor. Multiple individuals mentioned the desire to avoid any kind of morcellation of tissues, and to remove the specimens intact.

“There was a lot of discussion about the use of bags, and while it was thought that, intuitively, that that may have advantages in reducing dissemination of an unrecognized malignancy, the data to support that appears to be totally lacking at this point in time.

“Therefore, the conclusion is that we don’t know, through the use of the bags, to what extent, if any, we’re able to reduce the risk at this point.”

 


Panel Members: A Black Box Warning Is Insufficient

Power morcellators should be labeled with a black box warning, should it continue to stay on the market, some panel members said, adding that additional cautionary measures need to be adopted to ensure patients are aware of the risk.

“I don’t think a black box alone would be sufficient; I have no confidence that that would actually get to the patient,” said Paula Hillard, professor of obstetrics and gynecology at the Stanford University Medical Center. “So I would completely agree that a black box warning [should be accompanied by] a document that the patient and the physician would sign as a special control.”

Some panel members expressed concern that the warning would not be heeded, even by hospitals and physicians. Robert Mattrey, vice chairman of research and professor of radiology at the UC San Diego School of Medicine assured that the warning would have impact:

“When there’s a black box warning, everybody knows about it, whether on the drug side or the device side,” he said. “It’s difficult to avoid. Whether it trickles down to the consumer, I don’t know, but I think the medical community is aware of every black box that relates to their work.”

The warning does not protect the patient, Shriver said.

“What the weakness of a box warning is, we think the physician is accepting the risk, but they’re not, it’s the patient who is accepting the risk,” he said. “Not using the device on the market is the solution.”

Even with a containment system, the risk that accompanies power morcellators—with these warnings in place—may well encourage patients to seek other treatment options, Iglesia said.

“I think that even if you do mention a bag, there is never a 100 percent guarantee to prevent tissue fragment dissemination with this generation of power morcellators,” she said. “To some degree, I really do respect industry who are going to be looking at and hopefully inventing safer devices that don’t disseminate.

“But I don’t think that we can really say anything on a label, and quite frankly, if you have that label and the patient and the physician are both signing it, I think it’s going to bring the discussion of, ‘What are the alternatives again, doctor?’”

Even if the FDA allows power morcellators to stay in use, the black box label could ultimately drive the devices off the market, said Mark Talamini, professor and M.J. Orloff Family chair of the department of surgery at UC San Diego Medical Center.

“An equally plausible scenario is that, if this remains on the market with these sorts of warnings, they may disappear entirely, because I doubt they’re a large margin item for most of these device companies,” Talamini said. “If this remains on the market with this set of warnings, it may be very hard to find a power morcellator.”

 


FDA: A High-Priority Issue

The severity of spreading an unsuspected cancer is great, said Ben Fisher, director of FDA’s Division of Reproductive, Gastro-Renal, and Urological Devices in the Office of Device Evaluation.

“If the issue that was on the table was just morcellation of a truly benign tissue, none of us would be here today,” Fisher said in his closing remarks. “I think one of the major challenges we are facing is identifying the uterine sarcoma prior to any procedure.

“Now, when you look at risk, we talk about rate and severity, and we’ve talked about a lot of different numbers over the past two days: one in 350, one in 7,000. Although we may not agree on the actual number, I think it’s very encouraging that there are a number of parties already working in this area.

“It’s been said we should really look at this further because this is an important part to helping to inform not only the patients, but also the physician. Regardless of the rate, when we talk about risk, we also have to talk about severity.

“We’ve talked about mitigation strategies. We’ve talked a little about trying to identify low-risk populations. One of the things we talked about was imaging—is this a possible modality that, in the future, will improve to a point where we’re actually able to discriminate or to tell a difference between a fibroid and an LMS?”

FDA is cautious about making statements that would jeopardize innovation, Fisher said.

“The one thing we don’t want to do: FDA does not want to put forward a front that’s going to discourage technical innovation,” he said. “So, hopefully I got my point across when we were talking about bags—I’d like to expand that to a containment device because I think we are open to innovation and we want to encourage that.”

Fisher thanked the patient advocates for bringing the issue to the agency:

“In this situation—we’re talking about the morcellation of uterine fibroids—I think we all agree that there is an increased awareness and acknowledgement that there is a real public health issue here.

“I hope that, based on the actions that FDA has taken thus far, that everybody realizes that FDA considers this to be a high-priority issue.”

The FDA will be taking public statements on the issue through Aug. 11.

Will Craft contributed to this story.

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GYN Group: Open Surgery Would Cost More Lives than Morcellation

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