Review group disputes FDA’s power morcellator warning

A November 2014 Food and Drug Administration warning against the use of laparoscopic power morcellators in most women undergoing minimally invasive treatment for uterine leiomyomas was based on a “misleading analysis,” according to a published commentary and a related open letter sent to the FDA.

The authors – the 46 members of the Leiomyoma Morcellation Review Group – are requesting that the FDA modify the current guidance to “empower each woman to consider the pertinent issues and have the freedom to undertake shared decision-making with her surgeon to select the procedure which is most appropriate for her.”

The FDA guidance “was prompted by concern that if a patient had an undiagnosed leiomyosarcoma the morcellator might inadvertently spread tumor cells within the peritoneal cavity. We disagree with the methodology the FDA used to determine the prevalence of leiomyosarcoma among women presumed to have benign leiomyomas and the subsequent restrictions placed on the use of the morcellator, which currently deny many women the benefits of minimally invasive surgery,” Dr. William H. Parker of the University of California, Los Angeles, and his colleagues wrote on behalf of the Review Group (Obstet Gynecol. 2016;127:18-22. doi: 10.1097/AOG.0000000000001157).

Based on a literature review, the FDA estimated that 1 of every 458 women having surgery for presumed leiomyomas would be found to have an occult leiomyosarcoma.

“We challenge the calculation,” the authors wrote, explaining that the FDA searched medical databases using the terms “uterine cancer” and “hysterectomy or myomectomy,” and that because the term “uterine cancer” was required, studies in which cancer was not found or discussed were not identified. The Review Group also noted that all but one of nine studies reviewed by the FDA were retrospective, one was a non–peer-reviewed letter to the editor, and one was an abstract from an unpublished study. In addition, three leiomyosarcoma cases identified by the FDA do not meet current pathologic criteria for cancer and would now be classified as benign atypical leiomyomas.

When the non–peer-reviewed data are excluded, the prevalence of leiomyosarcoma among 12,402 women having surgery for presumed leiomyomas is 1 in 1,550 (0.064%); other recently published data found prevalence rates of 0 to 0.051%, according to the review group’s analysis.

Further, a severe restriction of morcellation based on the FDA communication warning against the use of laparoscopic morcellators in most women undergoing myomectomy or hysterectomy for treatment of fibroids would limit women with symptomatic leiomyomas to one option: total abdominal hysterectomy, the group wrote.

A number of procedures, such as vaginal hysterectomy, mini-laparotomy, and laparoscopic myomectomy, to name just a few, would be eliminated for women with leiomyomas larger than a 10-week pregnancy size.

The concerns expressed in the commentary and the open letter have been brewing since before the FDA warning was issued, and it was felt that the voices of those opposed to the restrictions were not fully heard, Dr. Daniel Clarke-Pearson, one of the authors of the commentary, explained in an interview.

Leiomyosarcoma is bad no matter how it is treated; even when removed intact, survival is poor, he said, explaining that a decision analysis using hypothetical assumptions suggested that outcomes are worse when the complications of abdominal surgery for leiomyomas are considered.

“We’re asking for a balanced presentation and that the pros and cons and risks and benefits be considered by the FDA and explained to the public,” said Dr. Clarke-Pearson, professor and chair of clinical research for the Gynecologic Oncology Program at the University of North Carolina, Chapel Hill.

The review group does not contend that the prognosis is not worse in cases when a leiomyosarcoma is morcellated, he said, noting that the findings of decreased early survival in a study published in the same issue of Obstetrics and Gynecology are not surprising. That population-based cohort study of all uterine sarcomas from 2006 to 2013 in an integrated health care system showed a decrease in survival at 1 year among women who underwent morcellation compared with those who did not (adjusted risk ratio, 5.12), according to Dr. Tina Raine-Bennett of Kaiser Permanente Northern California, Oakland, and her colleagues (Obstet Gynecol. 2016;127:29-39. doi: 10.1097/AOG.0000000000001187).

Rather, the overall risks and benefits should be considered to allow for informed consent among women in the context of good clinical judgment on the part of the surgeon, based, for example, on the patient’s age and risk of leiomyosarcoma, Dr. Clarke-Pearson said.

Also, research should continue in an effort to improve the identification of sarcomas prior to surgery, and to better assess techniques, such as the use of containment bags during morcellation, to determine if they can reduce risk and improve outcomes, he said.

The review group asks that a number of clinical recommendations be considered. For example, the group suggests that caution be exercised prior to recommending morcellation procedures for postmenopausal women because of a higher risk of leiomyosarcoma in that population, and that careful inspection for tissue fragments be undertaken following morcellation, with “copious irrigation of the pelvic and abdominal cavities to minimize the risk of retained tissue.

“Respecting women who have leiomyosarcoma, we conclude that the FDA directive was based on a misleading analysis. Consequently, more accurate estimates regarding the prevalence of leiomyosarcoma among women having surgery for leiomyomas should be issued. Women have a right to self-determination,” they wrote in the commentary.

Dr. Charles E. Miller, a clinical associate professor at the University of Illinois, Chicago, and a past president of the AAGL, applauded the work by Dr. Parker and his colleagues in putting together the analysis, but noted that there have been some positive effects of the FDA warning, namely that it challenged physicians and industry to “think outside the box” in creating methods to reduce potential leiomyosarcoma spread.

“I strongly believe that risk can be further decreased at time of morcellation – electronic versus cold knife, via laparoscopy, minilaparotomy, or vaginal if the morcellation is performed in a contained system (i.e. bag),” Dr. Miller said in an interview.

The FDA will likely approve a containment system designed by Dr. Tony Shibley in cooperation with Olympus, according to Dr. Miller. Also, Dr. Miller recently received approval from the FDA to perform an Investigational Device Exemption study on a multiport containment system that his minimally invasive gynecologic surgery team developed in conjunction with Espiner Medical, Ltd.

“It is my opinion, along with many others, that not only can the risk of inadvertent spread of leiomyosarcoma be minimized with contained morcellation, but risk of leiomyomatosis and bowel injury be significantly reduced as well,” he said.

Dr. Hal C. Lawrence, executive vice president and chief executive officer of the American College of Obstetricians and Gynecologists, also weighed in on the morcellation controversy.

“The conclusions of the paper’s authors largely reflect positions that ACOG has reiterated during the ongoing discussion about potential safety concerns with morcellation as well as its value in facilitating minimally invasive gynecologic surgery,” he said in a statement. “Without question, morcellation of an undiagnosed sarcoma can disseminate malignant tissue. However, by allowing some women to avoid the higher morbidity and mortality associated with open abdominal surgery, morcellation can also save lives.”

As a result of the continuing conversation about morcellation, ob.gyns. are “better able to evaluate each individual woman’s risk of an undiagnosed sarcoma, and to counsel her to receive the right approach for her own unique medical needs,” he added.

In a statement, an FDA spokesperson said that the agency’s recommendations have not changed. “We continue to believe that inclusion of a boxed warning and contraindications to the use of power morcellation for uterine fibroid removal in the majority of women is both appropriate and necessary. We welcome the continued scientific dialogue concerning the available evidence about benefits and risks associated with power morcellation and will notify the public if our recommendations change.” 

The authors of the commentary and open letter to the FDA, and Dr. Raine-Bennett and her colleagues, all reported having no conflicts of interest.

*This story was updated 12/9/2015

sworcester@frontlinemedcom.com

A November 2014 Food and Drug Administration warning against the use of laparoscopic power morcellators in most women undergoing minimally invasive treatment for uterine leiomyomas was based on a “misleading analysis,” according to a published commentary and a related open letter sent to the FDA.

The authors – the 46 members of the Leiomyoma Morcellation Review Group – are requesting that the FDA modify the current guidance to “empower each woman to consider the pertinent issues and have the freedom to undertake shared decision-making with her surgeon to select the procedure which is most appropriate for her.”

The FDA guidance “was prompted by concern that if a patient had an undiagnosed leiomyosarcoma the morcellator might inadvertently spread tumor cells within the peritoneal cavity. We disagree with the methodology the FDA used to determine the prevalence of leiomyosarcoma among women presumed to have benign leiomyomas and the subsequent restrictions placed on the use of the morcellator, which currently deny many women the benefits of minimally invasive surgery,” Dr. William H. Parker of the University of California, Los Angeles, and his colleagues wrote on behalf of the Review Group (Obstet Gynecol. 2016;127:18-22. doi: 10.1097/AOG.0000000000001157).

Based on a literature review, the FDA estimated that 1 of every 458 women having surgery for presumed leiomyomas would be found to have an occult leiomyosarcoma.

“We challenge the calculation,” the authors wrote, explaining that the FDA searched medical databases using the terms “uterine cancer” and “hysterectomy or myomectomy,” and that because the term “uterine cancer” was required, studies in which cancer was not found or discussed were not identified. The Review Group also noted that all but one of nine studies reviewed by the FDA were retrospective, one was a non–peer-reviewed letter to the editor, and one was an abstract from an unpublished study. In addition, three leiomyosarcoma cases identified by the FDA do not meet current pathologic criteria for cancer and would now be classified as benign atypical leiomyomas.

When the non–peer-reviewed data are excluded, the prevalence of leiomyosarcoma among 12,402 women having surgery for presumed leiomyomas is 1 in 1,550 (0.064%); other recently published data found prevalence rates of 0 to 0.051%, according to the review group’s analysis.

Further, a severe restriction of morcellation based on the FDA communication warning against the use of laparoscopic morcellators in most women undergoing myomectomy or hysterectomy for treatment of fibroids would limit women with symptomatic leiomyomas to one option: total abdominal hysterectomy, the group wrote.

A number of procedures, such as vaginal hysterectomy, mini-laparotomy, and laparoscopic myomectomy, to name just a few, would be eliminated for women with leiomyomas larger than a 10-week pregnancy size.

The concerns expressed in the commentary and the open letter have been brewing since before the FDA warning was issued, and it was felt that the voices of those opposed to the restrictions were not fully heard, Dr. Daniel Clarke-Pearson, one of the authors of the commentary, explained in an interview.

Leiomyosarcoma is bad no matter how it is treated; even when removed intact, survival is poor, he said, explaining that a decision analysis using hypothetical assumptions suggested that outcomes are worse when the complications of abdominal surgery for leiomyomas are considered.

“We’re asking for a balanced presentation and that the pros and cons and risks and benefits be considered by the FDA and explained to the public,” said Dr. Clarke-Pearson, professor and chair of clinical research for the Gynecologic Oncology Program at the University of North Carolina, Chapel Hill.

The review group does not contend that the prognosis is not worse in cases when a leiomyosarcoma is morcellated, he said, noting that the findings of decreased early survival in a study published in the same issue of Obstetrics and Gynecology are not surprising. That population-based cohort study of all uterine sarcomas from 2006 to 2013 in an integrated health care system showed a decrease in survival at 1 year among women who underwent morcellation compared with those who did not (adjusted risk ratio, 5.12), according to Dr. Tina Raine-Bennett of Kaiser Permanente Northern California, Oakland, and her colleagues (Obstet Gynecol. 2016;127:29-39. doi: 10.1097/AOG.0000000000001187).

Rather, the overall risks and benefits should be considered to allow for informed consent among women in the context of good clinical judgment on the part of the surgeon, based, for example, on the patient’s age and risk of leiomyosarcoma, Dr. Clarke-Pearson said.

Also, research should continue in an effort to improve the identification of sarcomas prior to surgery, and to better assess techniques, such as the use of containment bags during morcellation, to determine if they can reduce risk and improve outcomes, he said.

The review group asks that a number of clinical recommendations be considered. For example, the group suggests that caution be exercised prior to recommending morcellation procedures for postmenopausal women because of a higher risk of leiomyosarcoma in that population, and that careful inspection for tissue fragments be undertaken following morcellation, with “copious irrigation of the pelvic and abdominal cavities to minimize the risk of retained tissue.

“Respecting women who have leiomyosarcoma, we conclude that the FDA directive was based on a misleading analysis. Consequently, more accurate estimates regarding the prevalence of leiomyosarcoma among women having surgery for leiomyomas should be issued. Women have a right to self-determination,” they wrote in the commentary.

Dr. Charles E. Miller, a clinical associate professor at the University of Illinois, Chicago, and a past president of the AAGL, applauded the work by Dr. Parker and his colleagues in putting together the analysis, but noted that there have been some positive effects of the FDA warning, namely that it challenged physicians and industry to “think outside the box” in creating methods to reduce potential leiomyosarcoma spread.

“I strongly believe that risk can be further decreased at time of morcellation – electronic versus cold knife, via laparoscopy, minilaparotomy, or vaginal if the morcellation is performed in a contained system (i.e. bag),” Dr. Miller said in an interview.

The FDA will likely approve a containment system designed by Dr. Tony Shibley in cooperation with Olympus, according to Dr. Miller. Also, Dr. Miller recently received approval from the FDA to perform an Investigational Device Exemption study on a multiport containment system that his minimally invasive gynecologic surgery team developed in conjunction with Espiner Medical, Ltd.

“It is my opinion, along with many others, that not only can the risk of inadvertent spread of leiomyosarcoma be minimized with contained morcellation, but risk of leiomyomatosis and bowel injury be significantly reduced as well,” he said.

Dr. Hal C. Lawrence, executive vice president and chief executive officer of the American College of Obstetricians and Gynecologists, also weighed in on the morcellation controversy.

“The conclusions of the paper’s authors largely reflect positions that ACOG has reiterated during the ongoing discussion about potential safety concerns with morcellation as well as its value in facilitating minimally invasive gynecologic surgery,” he said in a statement. “Without question, morcellation of an undiagnosed sarcoma can disseminate malignant tissue. However, by allowing some women to avoid the higher morbidity and mortality associated with open abdominal surgery, morcellation can also save lives.”

As a result of the continuing conversation about morcellation, ob.gyns. are “better able to evaluate each individual woman’s risk of an undiagnosed sarcoma, and to counsel her to receive the right approach for her own unique medical needs,” he added.

In a statement, an FDA spokesperson said that the agency’s recommendations have not changed. “We continue to believe that inclusion of a boxed warning and contraindications to the use of power morcellation for uterine fibroid removal in the majority of women is both appropriate and necessary. We welcome the continued scientific dialogue concerning the available evidence about benefits and risks associated with power morcellation and will notify the public if our recommendations change.” 

The authors of the commentary and open letter to the FDA, and Dr. Raine-Bennett and her colleagues, all reported having no conflicts of interest.

*This story was updated 12/9/2015

sworcester@frontlinemedcom.com

A November 2014 Food and Drug Administration warning against the use of laparoscopic power morcellators in most women undergoing minimally invasive treatment for uterine leiomyomas was based on a “misleading analysis,” according to a published commentary and a related open letter sent to the FDA.

The authors – the 46 members of the Leiomyoma Morcellation Review Group – are requesting that the FDA modify the current guidance to “empower each woman to consider the pertinent issues and have the freedom to undertake shared decision-making with her surgeon to select the procedure which is most appropriate for her.”

The FDA guidance “was prompted by concern that if a patient had an undiagnosed leiomyosarcoma the morcellator might inadvertently spread tumor cells within the peritoneal cavity. We disagree with the methodology the FDA used to determine the prevalence of leiomyosarcoma among women presumed to have benign leiomyomas and the subsequent restrictions placed on the use of the morcellator, which currently deny many women the benefits of minimally invasive surgery,” Dr. William H. Parker of the University of California, Los Angeles, and his colleagues wrote on behalf of the Review Group (Obstet Gynecol. 2016;127:18-22. doi: 10.1097/AOG.0000000000001157).

Based on a literature review, the FDA estimated that 1 of every 458 women having surgery for presumed leiomyomas would be found to have an occult leiomyosarcoma.

“We challenge the calculation,” the authors wrote, explaining that the FDA searched medical databases using the terms “uterine cancer” and “hysterectomy or myomectomy,” and that because the term “uterine cancer” was required, studies in which cancer was not found or discussed were not identified. The Review Group also noted that all but one of nine studies reviewed by the FDA were retrospective, one was a non–peer-reviewed letter to the editor, and one was an abstract from an unpublished study. In addition, three leiomyosarcoma cases identified by the FDA do not meet current pathologic criteria for cancer and would now be classified as benign atypical leiomyomas.

When the non–peer-reviewed data are excluded, the prevalence of leiomyosarcoma among 12,402 women having surgery for presumed leiomyomas is 1 in 1,550 (0.064%); other recently published data found prevalence rates of 0 to 0.051%, according to the review group’s analysis.

Further, a severe restriction of morcellation based on the FDA communication warning against the use of laparoscopic morcellators in most women undergoing myomectomy or hysterectomy for treatment of fibroids would limit women with symptomatic leiomyomas to one option: total abdominal hysterectomy, the group wrote.

A number of procedures, such as vaginal hysterectomy, mini-laparotomy, and laparoscopic myomectomy, to name just a few, would be eliminated for women with leiomyomas larger than a 10-week pregnancy size.

The concerns expressed in the commentary and the open letter have been brewing since before the FDA warning was issued, and it was felt that the voices of those opposed to the restrictions were not fully heard, Dr. Daniel Clarke-Pearson, one of the authors of the commentary, explained in an interview.

Leiomyosarcoma is bad no matter how it is treated; even when removed intact, survival is poor, he said, explaining that a decision analysis using hypothetical assumptions suggested that outcomes are worse when the complications of abdominal surgery for leiomyomas are considered.

“We’re asking for a balanced presentation and that the pros and cons and risks and benefits be considered by the FDA and explained to the public,” said Dr. Clarke-Pearson, professor and chair of clinical research for the Gynecologic Oncology Program at the University of North Carolina, Chapel Hill.

The review group does not contend that the prognosis is not worse in cases when a leiomyosarcoma is morcellated, he said, noting that the findings of decreased early survival in a study published in the same issue of Obstetrics and Gynecology are not surprising. That population-based cohort study of all uterine sarcomas from 2006 to 2013 in an integrated health care system showed a decrease in survival at 1 year among women who underwent morcellation compared with those who did not (adjusted risk ratio, 5.12), according to Dr. Tina Raine-Bennett of Kaiser Permanente Northern California, Oakland, and her colleagues (Obstet Gynecol. 2016;127:29-39. doi: 10.1097/AOG.0000000000001187).

Rather, the overall risks and benefits should be considered to allow for informed consent among women in the context of good clinical judgment on the part of the surgeon, based, for example, on the patient’s age and risk of leiomyosarcoma, Dr. Clarke-Pearson said.

Also, research should continue in an effort to improve the identification of sarcomas prior to surgery, and to better assess techniques, such as the use of containment bags during morcellation, to determine if they can reduce risk and improve outcomes, he said.

The review group asks that a number of clinical recommendations be considered. For example, the group suggests that caution be exercised prior to recommending morcellation procedures for postmenopausal women because of a higher risk of leiomyosarcoma in that population, and that careful inspection for tissue fragments be undertaken following morcellation, with “copious irrigation of the pelvic and abdominal cavities to minimize the risk of retained tissue.

“Respecting women who have leiomyosarcoma, we conclude that the FDA directive was based on a misleading analysis. Consequently, more accurate estimates regarding the prevalence of leiomyosarcoma among women having surgery for leiomyomas should be issued. Women have a right to self-determination,” they wrote in the commentary.

Dr. Charles E. Miller, a clinical associate professor at the University of Illinois, Chicago, and a past president of the AAGL, applauded the work by Dr. Parker and his colleagues in putting together the analysis, but noted that there have been some positive effects of the FDA warning, namely that it challenged physicians and industry to “think outside the box” in creating methods to reduce potential leiomyosarcoma spread.

“I strongly believe that risk can be further decreased at time of morcellation – electronic versus cold knife, via laparoscopy, minilaparotomy, or vaginal if the morcellation is performed in a contained system (i.e. bag),” Dr. Miller said in an interview.

The FDA will likely approve a containment system designed by Dr. Tony Shibley in cooperation with Olympus, according to Dr. Miller. Also, Dr. Miller recently received approval from the FDA to perform an Investigational Device Exemption study on a multiport containment system that his minimally invasive gynecologic surgery team developed in conjunction with Espiner Medical, Ltd.

“It is my opinion, along with many others, that not only can the risk of inadvertent spread of leiomyosarcoma be minimized with contained morcellation, but risk of leiomyomatosis and bowel injury be significantly reduced as well,” he said.

Dr. Hal C. Lawrence, executive vice president and chief executive officer of the American College of Obstetricians and Gynecologists, also weighed in on the morcellation controversy.

“The conclusions of the paper’s authors largely reflect positions that ACOG has reiterated during the ongoing discussion about potential safety concerns with morcellation as well as its value in facilitating minimally invasive gynecologic surgery,” he said in a statement. “Without question, morcellation of an undiagnosed sarcoma can disseminate malignant tissue. However, by allowing some women to avoid the higher morbidity and mortality associated with open abdominal surgery, morcellation can also save lives.”

As a result of the continuing conversation about morcellation, ob.gyns. are “better able to evaluate each individual woman’s risk of an undiagnosed sarcoma, and to counsel her to receive the right approach for her own unique medical needs,” he added.

In a statement, an FDA spokesperson said that the agency’s recommendations have not changed. “We continue to believe that inclusion of a boxed warning and contraindications to the use of power morcellation for uterine fibroid removal in the majority of women is both appropriate and necessary. We welcome the continued scientific dialogue concerning the available evidence about benefits and risks associated with power morcellation and will notify the public if our recommendations change.” 

The authors of the commentary and open letter to the FDA, and Dr. Raine-Bennett and her colleagues, all reported having no conflicts of interest.

*This story was updated 12/9/2015

sworcester@frontlinemedcom.com