Comparison of uterine artery embolization and myomectomy: A long-term analysis of 863 patients

INTRODUCTION

Leiomyomata or uterine fibroids are the most common tumor affecting women with a prevalence of more than 80% in African-American women and nearly 70% in Caucasian women by age 50.^[1] Management and treatment of uterine fibroids result in an annual economic burden of up to 34.4 billion dollars in the United States.^[2]

Historically, fibroids have solely been treated by hysterectomy with fibroids remaining the most common indication for hysterectomy in the United States today.^[3,4] However, hysterectomy is associated with 3% rate of severe operative complications and a mortality rate of 3.8/1000 women with a higher postoperative risk in patients treated for fibroids compared to those treated for other indications.^[5]

Alternative and less morbid treatments for fibroids were later developed including myomectomy.^[6] Myomectomy has advantages over hysterectomy including decreased intraoperative visceral injuries and febrile morbidity. However, it has similar rates of blood loss and blood transfusion.^[7] In addition, there is a high rate of recurrence of fibroids following myomectomy with studies reporting rates ranging from 21 to 51%.^[8,9]

Uterine artery embolization (UAE) was first described in 1995 by Ravina et al. as an alternative therapy to surgery for patients with symptomatic fibroids and high operative risk, however later in the study, healthy women were included as well. Eleven of 16 patients reported resolution in their symptoms following the procedure.^[10] A few randomized control trials, including the REST and EMMY trials, have since been performed supporting the use of UAE for the treatment of fibroids.^[11,12] Most recently, Manyonda et al. published their randomized control trial comparing UAE and myomectomy in the New England Journal of Medicine. This study included 254 patients and reported similar rates of fibroid-related quality of life at 2 years and no difference in post-procedural menstrual bleeding scores between the two groups.^[13]

Despite UAEs proven efficacy and benefits, it continues to be underselected as a treatment for patients with symptomatic leiomyomata. A study performed by Cardozo et al. published in 2012 found that approximately 200,000 hysterectomies and 30,000 myomectomies are performed annually for the treatment of fibroids in the United States. By comparison, just thousands of UAEs are performed in this time frame.^[2] Similarly, Bonine et al. looking at treatment patterns in women in the United States with symptomatic fibroids between 2009 and 2014 found that the most common procedure performed was abdominal hysterectomy.^[14]

Given this continued low proportion of patients receiving UAE in lieu of the more invasive surgical alternatives, the aim of this study was to contribute to the available objective evidence to help better guide physicians in their clinical decision-making. The purpose of this study was to compare UAE and myomectomy for the treatment of symptomatic fibroids with the primary endpoint of reintervention rate to better evaluate the durability of both procedures. A number of secondary endpoints were also evaluated including post-procedural complications, differences in mean hemoglobin levels following the procedures, symptomatic improvement, and subsequent pregnancy outcomes.

MATERIAL AND METHODS

RESULTS

Baseline characteristics are detailed in Table 1. The UAE group was significantly older than the myomectomy group, with a median age of 46 (interquartile range [IQR] 42.0, 48.0) and 38 years old (IQR 34.0, 42.0), respectively (P < 0.0001). The UAE group also had a significantly higher rate of women with multiple fibroids, comorbid adenomyosis, pre-procedure menorrhagia, and patients with both pre-procedure menorrhagia and bulk symptoms. The median largest fibroid diameter was not statistically significant between the two groups, 6.2 cm in the UAE group and 7.2 cm in the myomectomy group (P = 0.56). Table 2 includes the breakdown of myomectomy procedures by type.

Results are summarized in Table 3. The median follow-up for the UAE and myomectomy groups was 7 and 7.3 years, respectively (P = 0.014). Both groups had comparable rates of secondary intervention, 8.9% in the UAE group and 11.2% in the myomectomy group (P = 0.26). Kaplan–Meier analysis was performed and did not show a significant difference in time to secondary intervention between the two groups [Figure 1].

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Figure 1:

Kaplan–Meier estimates for the cumulative incidence rate of secondary intervention. MYO: Myomectomy, UAE: Uterine artery embolization.

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Multivariate Cox proportional hazard model showed the interaction of age groups and treatment groups were significant. Therefore, stratified Cox proportional hazard model by age groups was applied and the results are shown in Table 4. For age less than 40 years old group (n = 262), treatment group was a significant factor with a hazard ratio of 3.76 (P=0.0099), which indicates that the UAE group had a 3.76 times chance of undergoing a secondary procedure compared to the myomectomy group. In this age group, 14.6% of patients in the UAE group and 6.5% of patients in the myomectomy group required a secondary intervention (P = 0.080). For age between 40 and 44 years old (n = 209), age was a significant factor with hazard ratio of 0.65 (P = 0.030), which means every 1 year increase in age decreased the chance of getting secondary procedure by 35%. However, treatment group was not a significant factor and patients following UAE and myomectomy in this age group had similar rates of secondary procedures, 3.9% versus 2.0%, respectively (P = 0.47). For the 45–49 years old group (n = 219), there were are no factors detected to that were be associated with the rate of secondary procedures. Reintervention rates were similar between the two groups, 3.9% and 6.4% in the UAE and myomectomy groups, respectively (P = 0.43).

The myomectomy group had a 3-fold higher rate of blood transfusion during the post-operative period defined as the first 6 months following the procedure and excluding intraoperative transfusion, 2.9% versus 0.9% in the UAE group (P = 0.028). Rates of pelvic infection during the post-operative period were not statistically significant between the two groups, 1.1% in the UAE group and 0.2% in the myomectomy group (P = 0.22). Both groups also had similar rates of rehospitalization, 2.7% and 2.9%, respectively (P = 0.82).

Four hundred patients in the UAE group and 273 patients in the myomectomy group reported menorrhagia pre-procedurally. Of these patients, a significantly higher number in the UAE group reported improvement in their symptoms following the procedure, 75.4% (n = 340) versus 49.5% (n = 204) in the myomectomy group (P > 0.0001). Both groups reported similar rates of improvement in bulk symptoms, 46.1% and 43.2% (P = 1.0), respectively.

In patients with pre-procedural anemia defined as a hemoglobin <12 g/dl (n = 227 in the UAE group, n= 190 in the myomectomy group), both groups experienced a significant rise in mean hemoglobin at one year. The mean hemoglobin rose by a mean difference (SD) of 1.8 (2.1) in the UAE group and 1.8 (2.5) in the myomectomy group (P < 0.0001 for both groups). The difference between the two groups was not statistically significant.

Six patients in the UAE group became pregnant following the procedure. Of these patients, three terminated their pregnancy, two had cesarean deliveries, and one had a spontaneous abortion. Of the patients in the myomectomy group, 84 became pregnant and 81.2% (n = 69) of these patients had successful cesarean or vaginal deliveries.

In patients who had pre-procedure MRI examinations (n = 451 in the UAE group and n = 412 in the myomectomy group), patients who had comorbid adenomyosis were identified and subgroup analysis was performed. Twenty-seven patients in the UAE group and 8 patients in the myomectomy group had comorbid adenomyosis confirmed on MRI. Three patients in each of these groups underwent a secondary procedure for a rate of 11.1% in the UAE group and 37.5% in the myomectomy group (P = 0.12). The group of patients with comorbid adenomyosis who underwent UAE reported a significantly higher rate of improvement in menorrhagia, 85.3% versus 50% in the corresponding myomectomy group (P = 0.028). Both groups reported similar rates of improvement in bulk symptoms, 48.1% and 50% (P = 0.68), respectively.

DISCUSSION

This study demonstrated comparable rates of secondary interventions following UAE and myomectomy over a 7-year follow-up period. However, stratified analysis by age group demonstrated a higher rate of secondary intervention following UAE in women 30–39 years of age. Women 40–49 years of age had similar rates of secondary intervention. UAE was also shown to result in lower rates of blood transfusion in the post-operative period and may be more effective in the treatment of symptomatic menorrhagia.

The increased rate of secondary intervention following UAE in patients age 30–39 years old is something that should be discussed with patients in this age group during the treatment decision-making process and weighed with the other attributes of the two procedures. Counterintuitively, although UAE is associated with higher rates of secondary interventions in this age group, patients reported higher rates of improvement in menorrhagia and equivalent rates of improvement in bulk symptoms compared to the myomectomy group. The reasons for this phenomenon cannot be definitively elucidated on retrospective review, however, may be related to the less invasive nature of UAE resulting in increased willingness to undergo a second procedure. Women 30–39 years old in the myomectomy group may also still desire fertility making them more hesitant to undergo a second procedure. Women who receive UAE are screened to ensure they do not desire future fertility and therefore they may be more inclined to undergo repeat procedures if their symptoms persist. In patients 40 years of age and older, the two procedures are equivalent in rate of secondary procedures. The equilibration at later ages is likely attributable to closer temporal relationship to menopause which is associated with improvement in fibroid symptoms.

The rate of secondary interventions for the UAE group was lower than rates reported in the randomized EMMY and REST trials. Five-year results from the EMMY and REST trials reported secondary intervention rates of 28.5% and 32%, respectively.^[11,12] This may be related to improved techniques as those trials were performed in the early 2000s shortly after UAE became an accepted treatment for fibroids. The majority of physicians performing UAEs in the EMMY trial actually performed less than 10 UAEs before the trial. In addition, improved technology may be contributory as polyvinyl alcohol (PVA) particles were the primary embolic agent used in the EMMY and REST trials. All patients in this study received tris-acryl gelatin microspheres (Embosphere, Merit Medical Systems Inc., South Jordan, Utah), which have been shown to be more effective than PVA particles in fibroid infarction.^[15] During the EMMY trial, 4 French or 5 French catheters were used for embolization, whereas now and in the majority of cases in the study, microcatheters are primarily used which may also contribute to improved outcomes. More recent studies report lower reintervention rates similar to the results of this study including the study performed by Scheurig-Muenkler et al. published in 2013, which included 308 patients and reported a reintervention rate of 15% at 5 years.^[16] Manyonda et al. in their recent randomized control trial reported a similar rate of reintervention in their UAE group of 15% at 2 years.^[13]

The rate of secondary intervention for the myomectomy group was similar to those reported in the literature. In the REST trial, only five patients in the myomectomy group had 5-year follow-up and of these only one required a subsequent myomectomy for a rate of 20%.^[11] Additional studies looking at laparoscopic myomectomy reported reintervention rates at 5 years between 6 and 14%.^[9,17,18]

The rates found for improvement in menorrhagia and bulk symptoms differed from previously reported rates. However, the literature overall varies widely. Rates of improvement in menorrhagia following UAE range between 51.2% and 92%.^[12,19-21] Hamoda et al. reported 51.2% rate of improvement in menorrhagia at 9–14 years following UAE in a study published in 2016 with a total of 197 patients.^[19] The Emmy trial reported a rate of 76% at 2 years.^[12] These rates overall have a downward trend based on the length of the follow-up period. The median follow-up of patients in this study was 7 years and symptomatic improvement was gauged based on follow-up examinations during this time. This may help to explain why the rate of improvement in menorrhagia is at the lower end of this range.

In terms of rates of improvement in bulk symptoms following UAE, the reported rates range between 48.8% at 9–14 years by Hamoda et al. and 66.2% at 2 years in the EMMY trial.^[12,19] Again, a similar downward trend with time is noted and the results of this study are similar to the rates reported by Hamoda et al. at 9–14 years.

This study reported similar to slightly higher rates to those reported in the literature in terms of symptomatic improvement following myomectomy. Obed et al. reported an improvement in menorrhagia of 33% in patients following myomectomy.^[22] Kramer et al. in a randomized control trial reported improvement in symptoms in 24% of patients in their myomectomy group, which included bulk symptoms and menorrhagia.^[23]

The differences in rates between patients without symptomatic improvement and secondary interventions are multifactorial and based on patient preferences. Women without improvement in their symptoms who did not undergo a secondary procedure may have made that decision based on unwillingness to undergo a second invasive procedure, preference for medical therapy, and possible negative attitude toward the procedures given their lack of improvement. The improvement in menorrhagia following UAE in patients with comorbid adenomyosis was even higher than that of the overall group. The rate of improvement in menorrhagia in the patients following myomectomy was similar in patients with adenomyosis and the overall group. This suggests that UAE may be a preferable treatment for patients with fibroids and comorbid adenomyosis. The efficacy of UAE in the treatment of patients with adenomyosis has been described in the literature.^[24]

Patients in the UAE group were more likely to get a second UAE or hysterectomy, whereas the patients in the myomectomy group were more likely to have a second myomectomy or hysterectomy. This is likely due to the personal preferences and practice patterns of individual clinicians involved in the patients’ care. In the future, it will be important to look at tertiary outcomes to see if these clinical practices can be changed and procedures chosen based on objective standards.

Despite the large patient cohort, only six patients in the UAE arm became pregnant during the follow-up period. This is likely secondary to the older age of this group and because patients who receive UAE are prescreened for the desire to preserve fertility. There continues to be a paucity of data regarding pregnancy outcomes in patients following UAE. Research performed by Pisco et al. looking at partial and complete UAE in patients who were unable to conceive which included 359 women actually found that UAE may improve fertility with a successful spontaneous pregnancy rate of 36.7% at 2 years.^[25] Larger patient datasets still need to be collected to validate these outcomes and to evaluate whether UAE is a safe option to offer patients desiring to preserve fertility. Given UAEs benefits when compared to myomectomy, it would be a good alternative for those women if it does not compromise future pregnancies.

The main strengths of this study are the large patient cohort, 7-year follow-up period, and multicenter involvement. The largest limitation of this study is the significant age difference between the two groups, which was mitigated through stratified analyses, and the retrospective study design. The use of CPT and ICD codes to capture outcomes such as secondary intervention rate and complications may also lead to error due to cases of misclassification. This study also only involved hospitals in the South California region and all patients were insured which may limit external validity. Location of the fibroids (submucosal, intramural, or subserosal) was difficult to attain consistently from the imaging reports and was unable to be included in the analysis.

Most commonly, patients present for consultation for uterine fibroids with menorrhagia and bulk symptoms. Given the results of this study, UAE may be the natural choice for many patients. In this patient subset, UAE resulted in higher rates of reported improvement in menorrhagia on follow-up visits when compared to myomectomy and comparable rates of improvement in bulk symptoms. In addition, UAE resulted in a lower rate of blood transfusions. This data should be considered by all clinicians counseling women in the treatment of their symptomatic uterine fibroids.

CONCLUSION

Overall, UAE and myomectomy have comparable rates of secondary intervention during a median 7-year follow-up period. However, in women between 30 and 39 years of age, UAE resulted in higher rates of secondary intervention. UAE may be more effective in controlling patients’ menorrhagia and has lower rates of post-procedural blood transfusions.