FDA panel recommends informed consent, labeling changes to address morcellator risk

SILVER SPRING, MD.  – A requirement for informed consent outlining the risks of morcellation of unsuspected malignancies in women treated with laparoscopic power morcellators for presumably benign fibroids was among the recommendations made by a Food and Drug Administration advisory panel.

On July 11, the second day of a two-day meeting of the FDA’s Obstetrics and Gynecology Devices Advisory Committee, panelists also supported adding a boxed warning to the labels of laparoscopic power morcellators (LPMs). Other suggestions and recommendations included identifying characteristics of patients or fibroids, physical exam findings, and other features that could help determine patients who may have a sarcoma before treatment, as well as strategies to mitigate risks during treatment.

"There should be some labeling or special controls" to ensure that women who are being considered for treatment with this device and their physicians "get the message that we do believe there is an increased risk" and that the device is contraindicated in patients with a known or suspected malignancy, said Dr. Carol Brown, a gynecologic cancer surgeon at Memorial Sloan Kettering Cancer Center, New York.

The advisory panel did not vote on any issues and was not asked whether LPMs should be taken off the market or reclassified as class III medical devices, which require clinical data for approval.

During testimony from women and relatives of those who had been diagnosed with stage 4 LMS after treatment that included morcellation for what was thought to be uterine fibroids, "a recurring theme" was that they had not been told that morcellation could be part of their treatment, and if they had known, they may not have agreed to that treatment and chosen an alternative, she pointed out.

The FDA convened the meeting to discuss the benefits, risks, and clinical role of LPMs in the treatment of women with uterine fibroids. Panelists also were told to discuss strategies that could be used to reduce the risks of morcellation disseminating cancerous tissue into the pelvis and abdomen of women with an unsuspected uterine sarcoma or leiomyosarcoma (LMS).

Concerns about this risk have received widespread attention this year. An FDA safety advisory was issued in April recommending that the use of LPMs during a hysterectomy or myomectomy in women with uterine fibroids be discouraged. The case of Dr. Amy Reed, an anesthesiologist who was diagnosed with stage 4 LMS after undergoing a hysterectomy with morcellation at the age of 40 for what was thought to be benign fibroids, also garnered media attention. She and her husband, Dr. Hooman Noorchashm, a cardiothoracic surgeon, are leading a campaign highlighting these risks, calling for a ban on the use of LPMs. They -- along with women who have had similar experiences, and husbands and sisters of women who died of disseminated LMS after undergoing morcellation for what was thought to be benign fibroids -- also spoke at the meeting. These speakers emphasized that they are aware of at least 130 such cases, despite the small number of cases reported to the FDA (21 as of June 2014).

In April, the FDA recommended that physicians discuss alternative treatment options with women who have symptomatic uterine fibroids. If power morcellation is considered the best option, the agency advised, women should be informed that their fibroids may contain cancerous cells and, if so, morcellation could significantly worsen their prognosis. Among women who undergo a hysterectomy or myomectomy for a presumed fibroid, about one in 350 have a uterine sarcoma, and about one in 500 have a leiomyosarcoma (LMS), the FDA estimates.

The currently available LPMs that are "cleared" for gynecologic indications are regulated as moderate-risk class II devices, which require little or no clinical data. The agency is considering requiring that clinical data be provided for LPMs used for gynecologic indications.

Panelists said that features and tools that could help determine whether a patient could have a sarcoma include an older age, certain symptoms, and genetic susceptibility (a history of retinoblastoma), some imaging techniques, as well as a history of pelvic radiation.

Two panelists – a surgical oncologist and a bioethicist – said that LPMs should not be used for gynecologic indications until better data are available.

"I have not seen anything in isolation or together" that could help predict whether a woman with presumed uterine fibroids has a leiomyosarcoma, said Dr. Craig Shriver, professor of surgery and director of the John P. Murtha Cancer Center at Walter Reed National Navy Military Medical Center, Bethesda, Md.

Referring to the tenets of considering all masses as cancer until proven otherwise, he said, "I have been perplexed over the last two decades watching the introduction of laparoscopic power morcellation techniques that is totally anathema to these and my core principles as a cancer surgeon," he said. Two days of testimony have "only more strongly reaffirmed my commitment and belief that at present, there is no safe way to offer laparoscopic power morcellation as part of any minimally invasive surgery," he added. They should be withdrawn from the market, reclassified as class III devices and studied in clinical trials, he recommended.

But Dr. Brown said that while she agreed with those principles, since fibroids are so common, banning the use of morcellation could result in “hundreds of thousands” of hysterectomies.

Specimen collection bags were used when LPMs were first introduced for gynecologic indications, but dropped over time. Use has increased recently as a result of the increased attention to the risks, but there is no evidence that bags are effective in reducing the risk of disseminating malignant cells in the peritoneal cavity, in the case of an unsuspected malignancy.

“If you are going to morcellate, and it can be done safely in a bag, then that should be encouraged,” said panelist Dr. Keith Isaacson, medical director of the Center for Minimally Invasive Gynecologic Surgery at Newton (Mass.) Wellesley Hospital. More work is needed to evaluate bags and the techniques for their use, and to determine how easy it is train clinicians in how to use them safely, he added. “I still believe that intuitively – and that’s all we have is intuition here – that it more likely mitigates the risk of upstaging a tumor if you morcellate within a containment system, such as a bag.”

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts, although occasionally a panelist is given a waiver, but not at this meeting.

Adverse events related to LPMs or other medical devices should be reported to the FDA.

[email protected]

This article has been updated 7/14/2014.

SILVER SPRING, MD.  – A requirement for informed consent outlining the risks of morcellation of unsuspected malignancies in women treated with laparoscopic power morcellators for presumably benign fibroids was among the recommendations made by a Food and Drug Administration advisory panel.

On July 11, the second day of a two-day meeting of the FDA’s Obstetrics and Gynecology Devices Advisory Committee, panelists also supported adding a boxed warning to the labels of laparoscopic power morcellators (LPMs). Other suggestions and recommendations included identifying characteristics of patients or fibroids, physical exam findings, and other features that could help determine patients who may have a sarcoma before treatment, as well as strategies to mitigate risks during treatment.

"There should be some labeling or special controls" to ensure that women who are being considered for treatment with this device and their physicians "get the message that we do believe there is an increased risk" and that the device is contraindicated in patients with a known or suspected malignancy, said Dr. Carol Brown, a gynecologic cancer surgeon at Memorial Sloan Kettering Cancer Center, New York.

The advisory panel did not vote on any issues and was not asked whether LPMs should be taken off the market or reclassified as class III medical devices, which require clinical data for approval.

During testimony from women and relatives of those who had been diagnosed with stage 4 LMS after treatment that included morcellation for what was thought to be uterine fibroids, "a recurring theme" was that they had not been told that morcellation could be part of their treatment, and if they had known, they may not have agreed to that treatment and chosen an alternative, she pointed out.

The FDA convened the meeting to discuss the benefits, risks, and clinical role of LPMs in the treatment of women with uterine fibroids. Panelists also were told to discuss strategies that could be used to reduce the risks of morcellation disseminating cancerous tissue into the pelvis and abdomen of women with an unsuspected uterine sarcoma or leiomyosarcoma (LMS).

Concerns about this risk have received widespread attention this year. An FDA safety advisory was issued in April recommending that the use of LPMs during a hysterectomy or myomectomy in women with uterine fibroids be discouraged. The case of Dr. Amy Reed, an anesthesiologist who was diagnosed with stage 4 LMS after undergoing a hysterectomy with morcellation at the age of 40 for what was thought to be benign fibroids, also garnered media attention. She and her husband, Dr. Hooman Noorchashm, a cardiothoracic surgeon, are leading a campaign highlighting these risks, calling for a ban on the use of LPMs. They -- along with women who have had similar experiences, and husbands and sisters of women who died of disseminated LMS after undergoing morcellation for what was thought to be benign fibroids -- also spoke at the meeting. These speakers emphasized that they are aware of at least 130 such cases, despite the small number of cases reported to the FDA (21 as of June 2014).

In April, the FDA recommended that physicians discuss alternative treatment options with women who have symptomatic uterine fibroids. If power morcellation is considered the best option, the agency advised, women should be informed that their fibroids may contain cancerous cells and, if so, morcellation could significantly worsen their prognosis. Among women who undergo a hysterectomy or myomectomy for a presumed fibroid, about one in 350 have a uterine sarcoma, and about one in 500 have a leiomyosarcoma (LMS), the FDA estimates.

The currently available LPMs that are "cleared" for gynecologic indications are regulated as moderate-risk class II devices, which require little or no clinical data. The agency is considering requiring that clinical data be provided for LPMs used for gynecologic indications.

Panelists said that features and tools that could help determine whether a patient could have a sarcoma include an older age, certain symptoms, and genetic susceptibility (a history of retinoblastoma), some imaging techniques, as well as a history of pelvic radiation.

Two panelists – a surgical oncologist and a bioethicist – said that LPMs should not be used for gynecologic indications until better data are available.

"I have not seen anything in isolation or together" that could help predict whether a woman with presumed uterine fibroids has a leiomyosarcoma, said Dr. Craig Shriver, professor of surgery and director of the John P. Murtha Cancer Center at Walter Reed National Navy Military Medical Center, Bethesda, Md.

Referring to the tenets of considering all masses as cancer until proven otherwise, he said, "I have been perplexed over the last two decades watching the introduction of laparoscopic power morcellation techniques that is totally anathema to these and my core principles as a cancer surgeon," he said. Two days of testimony have "only more strongly reaffirmed my commitment and belief that at present, there is no safe way to offer laparoscopic power morcellation as part of any minimally invasive surgery," he added. They should be withdrawn from the market, reclassified as class III devices and studied in clinical trials, he recommended.

But Dr. Brown said that while she agreed with those principles, since fibroids are so common, banning the use of morcellation could result in “hundreds of thousands” of hysterectomies.

Specimen collection bags were used when LPMs were first introduced for gynecologic indications, but dropped over time. Use has increased recently as a result of the increased attention to the risks, but there is no evidence that bags are effective in reducing the risk of disseminating malignant cells in the peritoneal cavity, in the case of an unsuspected malignancy.

“If you are going to morcellate, and it can be done safely in a bag, then that should be encouraged,” said panelist Dr. Keith Isaacson, medical director of the Center for Minimally Invasive Gynecologic Surgery at Newton (Mass.) Wellesley Hospital. More work is needed to evaluate bags and the techniques for their use, and to determine how easy it is train clinicians in how to use them safely, he added. “I still believe that intuitively – and that’s all we have is intuition here – that it more likely mitigates the risk of upstaging a tumor if you morcellate within a containment system, such as a bag.”

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts, although occasionally a panelist is given a waiver, but not at this meeting.

Adverse events related to LPMs or other medical devices should be reported to the FDA.

[email protected]

This article has been updated 7/14/2014.

SILVER SPRING, MD.  – A requirement for informed consent outlining the risks of morcellation of unsuspected malignancies in women treated with laparoscopic power morcellators for presumably benign fibroids was among the recommendations made by a Food and Drug Administration advisory panel.

On July 11, the second day of a two-day meeting of the FDA’s Obstetrics and Gynecology Devices Advisory Committee, panelists also supported adding a boxed warning to the labels of laparoscopic power morcellators (LPMs). Other suggestions and recommendations included identifying characteristics of patients or fibroids, physical exam findings, and other features that could help determine patients who may have a sarcoma before treatment, as well as strategies to mitigate risks during treatment.

"There should be some labeling or special controls" to ensure that women who are being considered for treatment with this device and their physicians "get the message that we do believe there is an increased risk" and that the device is contraindicated in patients with a known or suspected malignancy, said Dr. Carol Brown, a gynecologic cancer surgeon at Memorial Sloan Kettering Cancer Center, New York.

The advisory panel did not vote on any issues and was not asked whether LPMs should be taken off the market or reclassified as class III medical devices, which require clinical data for approval.

During testimony from women and relatives of those who had been diagnosed with stage 4 LMS after treatment that included morcellation for what was thought to be uterine fibroids, "a recurring theme" was that they had not been told that morcellation could be part of their treatment, and if they had known, they may not have agreed to that treatment and chosen an alternative, she pointed out.

The FDA convened the meeting to discuss the benefits, risks, and clinical role of LPMs in the treatment of women with uterine fibroids. Panelists also were told to discuss strategies that could be used to reduce the risks of morcellation disseminating cancerous tissue into the pelvis and abdomen of women with an unsuspected uterine sarcoma or leiomyosarcoma (LMS).

Concerns about this risk have received widespread attention this year. An FDA safety advisory was issued in April recommending that the use of LPMs during a hysterectomy or myomectomy in women with uterine fibroids be discouraged. The case of Dr. Amy Reed, an anesthesiologist who was diagnosed with stage 4 LMS after undergoing a hysterectomy with morcellation at the age of 40 for what was thought to be benign fibroids, also garnered media attention. She and her husband, Dr. Hooman Noorchashm, a cardiothoracic surgeon, are leading a campaign highlighting these risks, calling for a ban on the use of LPMs. They -- along with women who have had similar experiences, and husbands and sisters of women who died of disseminated LMS after undergoing morcellation for what was thought to be benign fibroids -- also spoke at the meeting. These speakers emphasized that they are aware of at least 130 such cases, despite the small number of cases reported to the FDA (21 as of June 2014).

In April, the FDA recommended that physicians discuss alternative treatment options with women who have symptomatic uterine fibroids. If power morcellation is considered the best option, the agency advised, women should be informed that their fibroids may contain cancerous cells and, if so, morcellation could significantly worsen their prognosis. Among women who undergo a hysterectomy or myomectomy for a presumed fibroid, about one in 350 have a uterine sarcoma, and about one in 500 have a leiomyosarcoma (LMS), the FDA estimates.

The currently available LPMs that are "cleared" for gynecologic indications are regulated as moderate-risk class II devices, which require little or no clinical data. The agency is considering requiring that clinical data be provided for LPMs used for gynecologic indications.

Panelists said that features and tools that could help determine whether a patient could have a sarcoma include an older age, certain symptoms, and genetic susceptibility (a history of retinoblastoma), some imaging techniques, as well as a history of pelvic radiation.

Two panelists – a surgical oncologist and a bioethicist – said that LPMs should not be used for gynecologic indications until better data are available.

"I have not seen anything in isolation or together" that could help predict whether a woman with presumed uterine fibroids has a leiomyosarcoma, said Dr. Craig Shriver, professor of surgery and director of the John P. Murtha Cancer Center at Walter Reed National Navy Military Medical Center, Bethesda, Md.

Referring to the tenets of considering all masses as cancer until proven otherwise, he said, "I have been perplexed over the last two decades watching the introduction of laparoscopic power morcellation techniques that is totally anathema to these and my core principles as a cancer surgeon," he said. Two days of testimony have "only more strongly reaffirmed my commitment and belief that at present, there is no safe way to offer laparoscopic power morcellation as part of any minimally invasive surgery," he added. They should be withdrawn from the market, reclassified as class III devices and studied in clinical trials, he recommended.

But Dr. Brown said that while she agreed with those principles, since fibroids are so common, banning the use of morcellation could result in “hundreds of thousands” of hysterectomies.

Specimen collection bags were used when LPMs were first introduced for gynecologic indications, but dropped over time. Use has increased recently as a result of the increased attention to the risks, but there is no evidence that bags are effective in reducing the risk of disseminating malignant cells in the peritoneal cavity, in the case of an unsuspected malignancy.

“If you are going to morcellate, and it can be done safely in a bag, then that should be encouraged,” said panelist Dr. Keith Isaacson, medical director of the Center for Minimally Invasive Gynecologic Surgery at Newton (Mass.) Wellesley Hospital. More work is needed to evaluate bags and the techniques for their use, and to determine how easy it is train clinicians in how to use them safely, he added. “I still believe that intuitively – and that’s all we have is intuition here – that it more likely mitigates the risk of upstaging a tumor if you morcellate within a containment system, such as a bag.”

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts, although occasionally a panelist is given a waiver, but not at this meeting.

Adverse events related to LPMs or other medical devices should be reported to the FDA.

[email protected]

This article has been updated 7/14/2014.