Considering the Risk of Leiomyosarcoma and Other Malignancies

Evaluation for the presence of leiomyosarcoma and other malignancies is discussed elsewhere. While generally positioned as an issue related to extirpative surgery in general, and myomectomy in particular, it is a consideration for any type of expectant, medical, ablative, vascular, or surgical management. While very difficult to diagnose absent a tissue diagnosis, the risks must be put into their proper perspective. The US FDA guidance was based on a perceived risk of 1/498, that greatly overestimates the risk which is likely closer to the 1/8,300 surgeries reported by Pritts in 2018. In addition to this low overall risk, it should be understood that these patients are selected for surgery, and, typically, are in an older age group. As a result, for most women under the age of 40 the risk of leiomyosarcoma should generally not affect any decision making.

The other type of neoplasia to be considered is endometrial cancer, as well as its typical precursor, endometrial intraepithelial neoplasia (EIN) also called atypical endometrial hyperplasia. Not only are women with a higher risk of EIN and endometrial cancer more readily identified because of risk factors (long-term exposure to endogenous unopposed estrogen; genetic risk of endometrial cancer) but accurate detection using endometrial sampling is far more easily achieved.

Expectant management is likely the most appropriate approach for most women with leiomyomas, since, in the vast majority of cases, the leiomyomas are not juxtaposed to the endometrium or are too small to contribute to symptoms, including infertility and recurrent pregnancy loss.

For many women affected by leiomyomas, fertility is a major concern. For some,  pregnancy is not a current goal, but there is a strong desire to conceive in the future. Indeed, many may be undecided regarding future fertility but, nevertheless, wish to preserve that option. Others with leiomyomas present with infertility as a "symptom". For them, decisions regarding management of their leiomyomas are a current issue that may or may not be accompanied by other contributors to infertility including male factor, ovulatory disorders, adenomyosis, endometriosis, and known or suspected tubal disease. In all of these instances, the clinician must be aware of the patient's goals and conduct the evaluation and selection of therapeutic options in a fashion that optimally preserves or enhances fertility. 

There are no medical management approaches that have been shown to enhance fertility, and, when hormonal suppression is used, conception is not possible. None of the image-guided techniques designed to ablate or devascularize leiomyomas have been extensively or even adequately evaluated for their ability to improve outcomes in those with infertility thought to be caused or contributed to by leiomyomas. This leaves myomectomy, by whichever route is thought to be the most appropriate, as the prevailing "gold standard", even if it too hasn't been subjected to rigorous and robust evaluation for pregnancy and related outcomes.

Another issue that must be considered is the impact of the various targeted procedures, such as myomectomy, vascular occlusion, and energy-based ablation on pregnancy itself, should it occur. While there are a number of series describing pregnancy outcomes with the various targeted therapies, few have been done evaluating outcomes by treated disease phenotype. Consequently, it is difficult to provide differential guidance to an individual who has had a FIGO Type 2-5 leiomyoma treated by MR-guided focused ultrasound (MRg-FUS) to one who has undergone a similar technique but to a single FIGO Type 6 tumor. Hypothetically, at least, one could surmise that the risks of uterine rupture would be greater with the Type 2-5 tumor and there are some case reports that seem consistent with this concern. Another type of evidence gap is the  potential effect, or efficacy, of the different routs of myomectomy, particularly  when of removing multiple submucous leiomyomas are removed simultaneously. We now have at least some evidence  that simultaneous hysteroscopic removal of opposing leiomyomas is associated with a high frequency of intrauterine adhesions (Yang 2008, Takasaki 2023); such evidence is relatively lacking for laparoscopic techniques.  These are only a few of the longstanding evidence gaps that challenge the counseling of patients regarding anticipated outcomes following procedures designed to remove or ablate leiomyomas.

In each of the therapeutic sections we will discuss what is known, and, what we don't know about these issues in an attempt to provide guidance to the clinician charged with management of patients in this clinical situation. Many evidence gaps remain; we must remain cognizant of this circumstance both for clinical care and in the design of basic, translational, and clinical research.

Medical therapy for leiomyomas can be categorized in a number of ways; one is by the mechanism of action. Some agents act directly on the endometrium while others work centrally to alter or eliminate the production of estradiol and progesterone from the ovary. Direct interference with leiomyoma growth is the mechanism whereby progesterone receptor modulators reduce leiomyoma volume.  An important concept to understand that medical therapy for leiomyomas is ineffective for the treatment of infertility or recurrent pregnancy loss.

Selective removal of leiomyomas is called myomectomy, a process that can be achieved trasvaginally usually with hysteroscopy, or transabdominally by laparotomy, or in a less invasive fashion by laparoscopic direction performed either with or without the assistance of a device called a "robot". Myomectomy remains the technique that is likely best suited for those women with infertility or who wish to maintain the uterus in a fashion suitable for future fertility.

Hysterectomy is an option reserved for those women with leiomyoma symptoms who have failed or are inappropriate for medical therapy, or targeted  leiomyoma therapy with myomectomy or image guided procedures. Patients must understand that future fertility will not be possible although gestational surrogacy will be an option. Hysterectomy may be either total, or supracervical (also called "subtotal") and the procedure can be performed by either vaginal or abdominal routes with the latter either laparotomic (via laparotomy) or laparoscopic, where it is directed with an endoscope and performed with instruments passed through two to four additional small-diameter cannulas or ports.