Leading Physicians Refute FDA Warning on Morcellation

Troy Brown, RN

December 08, 2015

A group of 49 physicians disagrees with recent restrictions placed by the US Food and Drug Administration (FDA) on the use of power morcellators during minimally invasive surgery in women with uterine leiomyomas.

"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," William H. Parker, MD, and colleagues for the Leiomyoma Morcellation Review Group write in a commentary published in the January issue of Obstetrics & Gynecology.

"This guidance was prompted by concern that if a patient had an undiagnosed leiomyosarcoma the morcellator might inadvertently spread tumor cells within the peritoneal cavity," the authors write.

"By focusing exclusively on the risk of leiomyosarcoma, the FDA failed to take into account other more common risks associated with surgery," they add. "Reduced mortality and fewer complications represent well-established benefits of laparoscopic surgery."

The FDA's restriction on morcellation, they say, unnecessarily put women at risk for these more common complications when other mechanisms, including preoperative assessments, could be used to reduce the real but small risk for leiomyosarcoma associated with morcellation.

The American Congress of Obstetricians and Gynecologists (ACOG) released a statement today coinciding with the publication by Dr Parker and colleagues. "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," said Hal C. Lawrence, MD, executive vice president and chief executive officer.

"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," he continued.

"As a result of the continuing conversation about morcellation, obstetrician-gynecologists 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."

A Faulty Analysis?

According to Dr Parker and colleagues, the FDA's warning was based on an analysis of nine studies that concluded that 1 in 458 women undergoing surgery for leiomyomas would have occult leiomyosarcoma. However, Dr Parker and colleagues note that the FDA's literature review included only published articles that referred to both "uterine cancer" and "hysterectomy," and thus selected studies that reported cancer findings and excluded those that did not.

The group also said that one report included in the agency's analysis was a non-peer-reviewed letter to an editor, which should not have been included, and that other cases in the analysis do not meet current pathological criteria for leiomyosarcoma. When Dr Parker and colleagues reanalyzed the data, excluding those questionable data, they estimated a rate of 1 (0.064%) in 1550 for occult leiomyosarcomas. Furthermore, a more recent meta-analysis of 133 studies found a prevalence of leiomyosarcoma of 1 (0.051%) in 1960, which is lower than the FDA's finding.

Dr Parker and colleagues acknowledge that there is a real, if small, risk for leiomyosarcoma and suggest that rather than doing away with morcellation altogether, clinical caution could be used to carefully select patients for laparoscopic surgeries. For example, they recommend exercising greater caution before recommending morcellation procedures for older postmenopausal women, in whom the risk for leiomyosarcoma is higher, and performing a preoperative endometrial biopsy on women aged 35 years and older who have irregular bleeding and presumed leiomyomas. Also, ultrasound and magnetic resonance imaging can be used to look for large irregular masses with areas of potential necrosis, which may suggest a leiomyosarcoma, and postoperative inspection of tissue fragments and irrigation of the pelvic and abdominal cavities after morcellation could be used to reduce the risk.

Not Everyone Is Convinced

Not everyone is convinced by the arguments of Dr Parker and colleagues, however. "The authors make a compelling case that the FDA overestimated the potential risk of leiomyosarcoma. However, despite the strength of the authors' arguments, there are also a number of important caveats to consider," Jason D. Wright, MD, from the Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, New York City, writes in an accompanying editorial.

The available studies have significant limitations, he notes. Most did not specifically study women who underwent morcellation. Studying the risk associated with apparent leiomyomas provides useful information, and that risk should not be judged equivalent to the risk associated with electric power morcellation specifically, Dr Wright writes.

"Second, a few of the studies were specifically designed for pathologic analysis of leiomyomas. This has the potential to result in undercapture of abnormalities if apparent leiomyomas are not thoroughly sampled and in the misclassification of smooth muscle tumors that are relatively uncommon in general," Dr Wright explains. "Finally, for those women who did undergo some type of morcellation, pathologic examination of morcellated specimens is difficult owing to fragmentation, again potentially undercapturing pathology."

Risk May Be Higher, New Study Suggests

In addition, a new study published alongside the article by Dr Parker and colleagues suggests the risk may not be as small as those authors estimate. Tina Raine-Bennett, MD, MPH, from the Division of Research, Kaiser Permanente Northern California, Oakland, and colleagues conducted a population-based cohort study in which they analyzed data from Kaiser Permanente's electronic health record and regional claims systems. They included northern California, southern California, and Colorado.

Between 2006 and 2013, 34,728 women underwent hysterectomies preformed for leiomyomas. During the same period, 321 women received a diagnosis of uterine sarcoma, 293 of whom were women who had had a hysterectomy. Among the women who underwent hysterectomy for leiomyomas, the incidence of occult uterine sarcoma was 1 of 278, or 3.60 (95% confidence interval [CI], 2.97 - 4.23) per 1000, hysterectomies, and the incidence of leiomyosarcoma was 1 of 429, or 2.33 (95% CI, 1.83 - 2.84) per 1000, hysterectomies.

After adjustment for race and ethnicity, the risk for occult uterine sarcoma and leiomyosarcoma in those patients aged 50 years and older was significantly higher compared with that in younger women. In addition, women aged 60 years and older had a significantly greater risk for occult low-grade and endometrial stromal sarcomas and high-grade endometrial sarcomas compared with women who were younger.

The unadjusted probability of 3-year disease-free survival for those with stage I leiomyosarcomas was 0.54 (95% CI, 0.42 - 0.64) with no morcellation, 0.19 (95% CI, 0.01 - 0.54) with power morcellation, and 0.51 (95% CI, 0.30 - 0.69) with nonpower morcellation.

"Although the plots suggest decreased probability of survival for power morcellation, there was no significant difference among all groups (P=.15) or between power morcellation and no morcellation (P=.29) or between nonpower morcellation and no morcellation (P=.88)," the researchers write.

The unadjusted probability of 3-year overall survival for those with stage I leiomyosarcoma was 0.64 (95% CI, 0.52 - 0.74) for no morcellation, 0.75 (95% CI, 0.31 - 0.93) for power morcellation, and 0.68 (95% CI, 0.46 - 0.83) for nonpower morcellation.

The researchers found no significant difference among all of the groups, between the power morcellation and no morcellation groups, or between the nonpower morcellation and no morcellation groups.

The authors have disclosed no relevant financial relationships.

Obstet Gynecol. 2016;127:7-9, 18-22, 29-29.

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