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by the FDA were retrospective, one was a non–peer-reviewed letter to the editor, and one was an abstract from an unpublished study.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.