Ahead of the publication of the Randomised Study of Embolisation and Surgical Treatment for Uterine Fibroids (REST) results - due out in March - there have been renewed calls for more randomised controlled trials to finally determine whether uterine artery embolisation (UAE) is a good alternative to hysterectomy in the treatment of uterine fibroids.
Preliminary results from the EMbolisation versus hysterectoMY (EMMY) trial, published in September 2005, were inconclusive in establishing the long-term efficacy of UAE. Principal investigator Professor Jim Reekers, Amsterdam, the Netherlands, concluded: " Our study cannot support the suggestion made by others that UAE has a lower complication rate than hysterectomy; again stressing the need for randomised studies." His calls were echoed by Dr James Spies, head of the Fibroid Registry for Outcomes Data (FIBROID) registry, which also released data recently. He said: "The next step in fibroid research is to design direct comparative studies between the various therapies to provide data as to which patients are best suited for each treatment."
It is interesting to note that there are no randomised clinical trials currently underway in the North America, which is peculiar considering the numbers of women undergoing UAE. There have been suggestions that this is because a significant number of gynaecologists who have a powerful influence on the US government sit on the boards that make these decisions. Gynaecologists have a substantial vested interest in keeping the status quo.
The EMMY trial
The EMMY trial is a multi-centre randomised controlled trial of UAE versus hysterectomy in the treatment of symptomatic uterine fibroids. It recruited 177 patients who were randomised to UAE (n=88) or hysterectomy (n=89) after being diagnosed with symptomatic fibroids and menorrhagia as documented by history, physical and ultrasound. Complications during UAE surgery included the need for procedure conversion, haematomas, emboli and nausea, while for the hysterectomy group they were one anaesthetic allergic reaction and a torn rectus muscle. One patient in each group developed a pulmonary emboli post procedure. After discharge the UAE group experienced the most cases of readmission for nausea, fever, pneumonia caused by asthmatic disease, incomplete fibroid expulsion, and one case of septicaemia. One surgical repair of a vesicovaginal fistula was required in the hysterectomy group.
Discussing the results, Reekers concluded, "Overall, major and minor complication rates in both groups were comparable, but minor complications in the period between discharge and the first six-week visit were significantly higher in the UAE group."
Reekers comments were supported by Dr Woulter Hehenkamp, gynaecology department, Amsterdam Academic Medical Center, who commented, "We could not find any differences in major complication rates between UAE and hysterectomy. Unsuccessful UAE procedures, however, seem to occur more often than previously reported. Hospital stay is significantly shorter for UAE. The higher minor complication rate after discharge in the UAE group, as well as the readmission rate and unscheduled visits, emphasise the need for careful follow-up and clear instructions to the patient. Although the study results provide support for UAE, the question as to whether UAE is a good alternative to hysterectomy depends on the balance of efficacy, costs and quality of life, and still remains to be answered."
And there are still questions to be answered. According to the US Hysterectomy Educational Resources and Services (HERS) Foundation, twice as many women in their 20s and 30s as women in their 50s and 60s have hysterectomies. HERS also believes a lot of hysterectomies are being carried out unnecessarily. The Foundation sometimes refers cases to board-certified gynaecologists - and so far 98% of women referred have been told that they did not need a hysterectomy.
The rate of hysterectomies in the US is high compared to other industrialised countries. American women are twice as likely to have a hysterectomy as women in England and four times as likely to have one as women in Sweden. Doctors in France almost never perform a hysterectomy for fibroids, which account for one-third of the hysterectomies done in the US.
Despite the lack of results from a randomised controlled trials, results from the various studies in the US have shown that UAE is safe and effective and is a valid treatment option for those women wishing to avoid a hysterectomy.
The FIBROID registry
FIBROID, headed by Spies, professor and chief of service, Department of Radiology, Georgetown University Hospital (GUH) and vice-chair of the Society of Interventional Radiology Foundation, is the largest, multi-centre, prospective voluntary registry on any procedure for benign uterine fibroids. The registry is a collaborative effort of the Society of Interventional Radiology Foundation, the Duke Clinical Research Institute, the FDA, and corporate supporters.
The registry is designed to follow the real world outcomes for UAE as it becomes a mainstream treatment widely available across the US, including collecting data on symptom relief, quality of life, subsequent care, satisfaction with outcome and menstrual status of 1,701 women (from the 3,166 who initially registered) who underwent UAE. The results show that more than 85% of women have had significant improvement in symptoms, including 82% who were satisfied with their level of improvement. In addition, the outcomes highlighted that women's quality of life scores improved significantly, and only 2.9% of patients required a hysterectomy within a year of having UAE.
The women showed a significant improvement in symptoms. Compared with baseline scores, 90% showed an improvement of greater than 10% on symptom scores on the health-related quality of life (HRQL) scale at both six months and one year. After one year, the mean HRQL score was 86.5, and the mean symptom score on the uterine fibroid symptom quality of life scale was 19.2; both represented significant improvements from baseline and were in the range for normal subjects.
Spies said that as well as marked improvement in both symptom and quality of life scores, there were relatively few complications and hospitalisations, and in general most patients were satisfied with the outcome. After one year, approximately 80% of the women said they would recommend UAE to others. In addition, most women reported a dramatic improvement in sexual function, although some reported no significant change, and 6-7% reported a decrease.
"The registry is important not only because of its size, but also because of the diversity of sites that participated. These results demonstrate that UAE can be safe and very effective beyond the academic or specialised centres. It shows a high rate of efficacy, even when performed in a wide variety of practice settings by interventional radiologists with differing levels of experience in performing the procedure," said Spies. "The registry is also important as it is one of the few efforts ever undertaken to study the efficacy of a procedure as it disseminates into broad practice, and this is the first such effort for a fibroid therapy".
Other independent trials
Separately, a five-year study conducted at the GUH, designed to determine the long-term outcome of patients receiving UAE for the relief of symptoms from fibroid tumours, has reported that 73% of patients have continued relief at five years with these patients needing no other major therapies.
From the initial cohort of 200 women, 95% completed follow-up at one year, 80% at two years, 91% at three years, 89% at four years, and 91% at five years. Three patients died during the five-year follow-up: two from unrelated cancer and one from heart disease. A total of 20% of 182 patients who completed five-year follow-up had failed treatment or fibroid recurrence. In this group, 25 had hysterectomies, six had myomectomies (surgical fibroid removal), and three had repeat embolisations. None of the hysterectomies were performed as a result of the complications of embolisation and at least four were due to a condition other than recurrent fibroids.
"This is a major step for the field," said Spies, principal investigator of the study. "What this study says is that the minimally-invasive UAE is an effective treatment longterm, with a recurrence rate of 20% similar to myomectomy, which has recurrence rates of 20-40% at five years. Many patients and gynaecologists have been interested in knowing how well UAE will perform in the long run and this study provides the first data to begin to answer that question.
"By five years, some of the women developed new fibroids in the uterus and began having symptoms again," commented Spies. "Some of our patients decided to have a hysterectomy and others were treated again with UAE. This is the case with any of the uterine-sparing treatments. Growth of new fibroids is possible and we saw this occurring in some patients during the later part of follow-up in this study. Given the durability of UAE demonstrated in this study, it will allow most women to avoid hysterectomy, which remains the most common therapy offered (in the US) today. Only 13.5% of patients in this study underwent hysterectomy during the course of follow-up. The women most likely to go on to subsequent intervention were those with single, very large fibroids. On the other hand, women with large numbers of smaller fibroids were less likely to fail."
Spies and his associates presented data on the five-year follow-up in a poster presentation at the International Congress on Uterine Leiomyoma Research, sponsored by the National Institutes of Health.
Separately, a literature review based on three previous studies covering 297 women, featured in the January 2006 issue of The Cochrane Library, has revealed that compared to traditional surgery, UAE results in a shorter hospital stay and a quicker return to everyday activities.
The review, led by Dr Janesh Gupta of the University of Birmingham, Birmingham Women's Hospital, UK, looked at two studies comparing UAE to hysterectomy. The third study compared UAE with myomectomy in women wishing to preserve their fertility. The Cochrane Review showed that up to 40% of women aged 40 and older have fibroids, with the incidence dropping after menopause. UAE of fibroid tumours is successful for about 85% of the women who choose this treatment. Most women can return to normal activities after one week, compared to six weeks or more after hysterectomy. Clinical success is measured by improvement in fibroid-related symptoms such as heavy bleeding and fibroid volume, which UAE decreased by 30-46% in two trials.
However, UAE was associated with a higher rate of minor complications following the procedure, such as vaginal discharge, bruising at the puncture site, pain, fever, nausea and vomiting. Women who underwent UAE had more unscheduled clinical visits and higher hospital readmission rates after leaving hospital compared with hysterectomy. But there were no statistically significant differences in rates of major complications between the two groups.
MRI and patient selection
Finally, according to the results of a study featured in the November edition of the Journal of Vascular and Interventional Radiology (2005; 16: 1465-1471) and conducted at Northwestern University Medical School, Chicago, Illinois, magnetic resonance imaging (MRI) improves the selection process for who should receive UAE.
Interventional radiologist and study author, Dr Howard B Chrisman, said that MRI allowed the investigators to clearly outline the location of each fibroid, determine if it is viable for treatment non-surgically, rule out misdiagnosis, identify which treatments are best suited for each patient and avoid ineffective treatments.
Women typically undergo an ultrasound at their gynaecologist's office as part of the evaluation process to determine the presence of uterine fibroids. However, Chrisman commented that this rudimentary imaging tool for fibroids is limited, as it does not show other underlying diseases or all the existing fibroids. The study was undertaken to assess the incidence of non-viable leiomyomas in patients referred for UAE with use of contrast material-enhanced pelvic MRI and to determine the effect of this information on interventional radiologists' decision to perform UAE or consider other treatment options.
The researchers recruited 100 women all of whom had previously completed both a gynaecologic and clinical exam. Researchers recorded the leiomyoma locations (ie, submucosal, intramural, subserosal), volume (length, width, height), and percent non-enhancement, and the measurements were divided into four categories (0-25%, 25-50%, 50-75%, 75-100%).
A total of 94 women underwent MRI examinations that revealed 381 leiomyomas that exceeded 3cm in each dimension. Twenty-one patients (22%) did not receive embolisation based on the findings of preprocedural MRI. In six patients (6%), there were nine non-viable dominant tumours with an average size of 7.8cm. These cases were not treated with UAE. Another 15 patients (16%) did not undergo UAE based on other MRI findings (including uterine size, presence of isolated adenomyosis and endometrial lesions). Sixty-eight patients (72%) had UAE.
Chrisman added that MRIs are excellent education tools for patients because the fibroids are even visible to an untrained eye, so women can see exactly what is happening inside their uterus. "By working with a patient's gynaecologist, interventional radiologists can use MRIs to enhance the level of patient care through better diagnosis, better education, better treatment options and better outcomes," he added.
"For the women who come to us suffering from uterine fibroids and do not want surgery or a hysterectomy, an MRI lets us see if she is a candidate for minimally invasive embolisation, a procedure that would have her treated and at home the next day. Using an MRI rather than ultrasound is like listening to a digital CD rather than a record, the quality is better in every way," Chrisman concluded.
Further proof, either way of the long-term results of UAE vs surgery, is expected from the Scottish REST to be published in March 2006.
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