Responding to the FEMME trial: “UAE should be considered whenever myomectomy is proposed”

Responding to the results of the FEMME (Fibroids with embolization or myomectomy to measure the effect on quality of life) trial, James Spies suggests that uterine artery embolization (UAE) is a favourable treatment option over myomectomy in many patients, as they take into consideration the recovery times and weigh up the benefits of having a minimally invasive procedure versus undergoing an open, operative one. “The important takeaway from the study is that both these treatments are highly effective and they produce comparable outcomes in this population,” he writes.

With the recent publishing of the FEMME trial outcomes in the New England Journal of Medicine,¹ we gained additional insight into the outcomes of UAE, this time in a head-to-head comparison with myomectomy. Myomectomy has had growing acceptance in recent years as a first choice among surgical options for fibroids. Where myomectomy used to be limited to those who wished to have children in the future, there is a growing body of data suggesting that outcomes are similar to hysterectomy in women beyond their primary childbearing years,² and it has been promoted by some in the gynaecology community as a preferred uterine-sparing treatment. It is in this context that we evaluate the FEMME study.

At first glance, some might be disappointed that the primary outcome from this study, the change in the quality of life score from the UFS QOL, showed a modest advantage for myomectomy, about eight points on a scale of 0 to 100. Higher scores on this scale reflect better quality of life. This was the primary conclusion reported in the abstract. However, when one looks closer some important points become clear. First, an eight-point difference is a modest difference at best, not reflecting a clinically important difference. As the authors note, the confidence interval suggests a range from no difference to a moderate 15-point difference.

The second important point is that, despite randomisation, the myomectomy group had lower baseline quality of life scores. This is a statistical aberration but with a direct impact on the primary outcome, which was the change in quality of life score. The final quality of life score was 80 for UAE patients and 84 for myomectomy patients, a minimal difference, below the threshold of what constitutes a clinically-important difference for this questionnaire.

A final point is that the more important measure on this questionnaire is the symptom score, which also showed a small, not clinically-important difference at six months in favor of myomectomy and no statistically significant difference at 12 months and two years. These findings confirm an earlier study using the same questionnaire comparing the outcomes of UAE, myomectomy, and hysterectomy with normal controls,³ in which myomectomy and UAE had similar quality of life and symptom scores.

So, the final scores are comparable, as were the safety and the limited fertility outcomes. The important takeaway from the study is that both these treatments are highly effective and they produce comparable outcomes in this population. When women choose a treatment for fibroids, they take a range of factors into consideration, including the outcomes mentioned, but also the time for recovery and time away from normal activities. In most cases, they will be comparing open operative myomectomy to a minimally invasive procedure, and many women are likely to believe that UAE is a better choice for them.

Having said that, the FEMME trial was not powered to address reproductive outcomes and, despite comparability in the very limited data presented, we cannot conclude that the reproductive outcomes are the same. There has only been one randomised trial reporting on reproductive outcomes of UAE versus myomectomy,⁴ and it showed an advantage for myomectomy. However, the data were not strong, and this lead the most recent Cochrane Review in 2012 to conclude that there was weak evidence favoring myomectomy over UAE for those seeking to become pregnant—to quote: “There was some indication that UAE may be associated with less favourable fertility outcomes than myomectomy, but it was very low quality evidence from a subgroup of a single study and should be regarded with extreme caution (live birth: odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08–0.84; pregnancy: OR, 0.29; 95% CI, 0.10–0.85, one study, 66 women”.⁵

The FEMME trial investigators are to be congratulated on completing a randomised trial comparing these two therapies. The study has contributed significantly to our knowledge of these two therapies, demonstrating that the two procedures provide very similar outcomes and, while each patient’s circumstances are different, UAE should be considered whenever myomectomy is proposed.

James B Spies is an interventional radiologist at MedStar Georgetown University Hospital, Washington, DC, USA.

References:

1. Manyonda I, Belli AM, Lumsden MA, Moss J, McKinnon W, Middleton LJ, et al. Uterine-Artery Embolization or Myomectomy for Uterine Fibroids. N Engl J Med. 2020;383(5):440-51.
2. Wallace K, Zhang S, Thomas L, Stewart EA, Nicholson WK, Wegienka GR, et al. Comparative effectiveness of hysterectomy versus myomectomy on one-year health-related quality of life in women with uterine fibroids. Fertil Steril. 2020;113(3):618-26.
3. Spies J, Bradley L, Guido R, Maxwell GL, Levine BA, Coyne K. Outcomes for leiomyoma therapies: Comparison with normal controls. Obstet Gynecol. 2010;116:641-52.
4. Mara M, Maskova J, Fucikova Z, Kuzel D, Belsan T, Sosna O. Midterm clinical and first reproductive results of a randomized controlled trial comparing uterine fibroid embolization and myomectomy. Cardiovasc Intervent Radiol. 2008;31(1):73-85.
5. Gupta JK, Sinha A, Lumsden MA, Hickey M. Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database Syst Rev. 2012;5:CD005073.