BBI Contributing Editor

SCOTTSDALE, Arizona At a mid-April gathering of the most forward-thinking gynecologists from around the world, a procedure performed by interventional radiologists was acknowledged as having beneficial results for the treatment of fibroids, or non-cancerous tumors within the uterus. That topic, along with others, was presented during a symposium sponsored by the American Association of Gynecologic Surgeons (AAGL; Santa Fe Springs, California) on "The Contemporary Management of Uterine Fibroids." Of the 35,000 ob/gyns in the U.S., about 10,000 of them actively perform surgery and 4,400 of those are members of the AAGL. The 150 attendees at this conference represented the leading authorities and early adopters who routinely pave the way for new technology to make its way into the domain of the community-based gynecologist.

This year, 5 million women between the ages of 20 and 49 will experience the symptoms of fibroids. That is why the focus of this conference was the management of patients with fibroids, including the criteria for selection of the various diagnostics, drugs, surgeries, embolization and all other interventions available.

The fact that an international conference was held solely for the treatment of fibroids confirms that this is a very new field of study. Up until only a few years ago (and still prevalent in less-advanced areas of this country), a hysterectomy was performed whenever a woman presented with symptoms due to fibroids. Now patients are better educated and are demanding a less invasive treatment because 1) they want to return to normal activities earlier than with a major surgery, 2) they haven't completed their families and want to maintain their fertility, or 3) they prefer not to have a healthy organ removed unnecessarily. This patient demand has driven the market to respond with a variety of alternatives to hysterectomy for symptomatic fibroids.

Medical management

Often the first treatment of choice is medical management, usually with a six-week trial of GnRH agonists which shrinks all the fibroids by about 40%. This is effective much of the time in eliminating the patient's symptoms, but not all patients are willing to tolerate the side effects, which are similar to being thrown into immediate menopause. Some patients can experience up to two years of symptom-free life after one six-month treatment with GnRH agonists. In a presentation by Andrew J. Brill, MD, of the University of Illinois at Chicago, a small study of 30 patients who had been treated pharmaceutically for their fibroids and then offered the choice of another drug treatment or surgery, 20 of them (or two-thirds) elected to repeat the drug treatment and avoid surgery altogether. (However, it was another speaker's impression that when offered the choice of these drugs or an intervention, many patients opt for the intervention.) Another drug that has been used to treat fibroids is RU486 or mifepristone, which in one study also reported on by Brill, reduced myoma growth by 49%, but had similar side effects as GnRH agonists. A new drug in Phase II clinical trials, asoprisnil (J867), shows a high degree of effectiveness in treating fibroids without any of the side effects of other drugs mentioned. Both the size of the fibroid and bleeding decreased while there were no side effects reported using this drug. When approved, asoprisnil could reduce the number of interventional procedures for fibroids, including potential embolization cases.

Other treatment interventions

The new thinking on interventions reported at this conference is that a physician can no longer treat all fibroids the same way. The cause of the symptoms not just the presence of fibroids must be addressed specifically. The physician must present all of the available options, their risks and the rationale for them to their patients. If medical management is not utilized, fibroids are surgically removed one at a time with a scalpel, electro surgery, radiofrequency, cryosurgery or high-frequency focused ultrasound (HIFU).

Regardless of excision method, the fibroids will recur. Office-based procedures will be the gold standard, but currently there are none routinely performed in an office setting due to anesthesia requirements and reimbursement regulations. Three papers presented touted the efficacy of combining a myomectomy procedure with endometrial ablation to eliminate bleeding. It is hard to believe that payors will tolerate a "double procedure" once a single procedure that eliminates all fibroids permanently becomes widespread. This new procedure is called uterine artery embolization.

Interventional radiologists (IRs) refer to the procedure that blocks blood flow to the uterus as uterine fibroid embolization or UFE. Gynecologists refer to the same procedure as uterine artery embolization or UAE. UAE and UFE are one and the same procedure, being performed by an interventional radiologist, having interchangeable nomenclature depending on who is addressing it. Uterine artery occlusion (UAO), or ligation, is a procedure being tried by gynecologists as their method of achieving the same results. UAO is different than UFE or UAE in that an external mechanical occlusion of the artery occurs, and is performed by a gynecologist, rather than an interior "plugging" of the artery performed by an interventional radiologist.

The size of the UFE market, as performed by interventional radiologists, is estimated to peak in the years 2003-2004 to about 30,000 procedures performed annually worldwide. This is based on the assumption that gynecologists will be performing uterine artery occlusions (UAOs) and no longer referring cases to interventional radiologists starting in 2004. It is important to note that these numbers are primarily U.S., since most places outside of the U.S. still treat fibroids by removing the uterus.

Radical change in thinking observed

Last November at the annual AAGL conference, uterine artery embolization (UAE) was barely discussed, other than with reluctance. Less than five months later at this AAGL-sponsored conference, embolization was a hot topic. At several panel discussions and interactive sessions, UAE was embraced as the intervention of choice for treating most fibroids. But gynecologists are not going to allow interventional radiologists to continue to perform these procedures for long, because the gynecologist does not want to lose this patient from his practice, does not want to lose the potential revenue for treating this patient, and does not want to treat the complications, if any, of a procedure performed by an IR. Early experience with UAE patients resulted in the gynecologists receiving phone calls from patients in the middle of the night who were in extreme pain from the UAE that the interventional radiologist performed. In addition, when gynecologists refused to refer their patients to an interventional radiologist for a UAE, those patients were lost from their gynecology practice. This unattractive early experience led many gynecologists to avoid UAE referrals altogether.

Just since last November's AAGL meeting, when UAE was still being shunned, there has been a remarkable move to embrace the uterine artery embolization procedure. In this group of forward-thinking gynecologists, there was a decided turn of opinion that this procedure is better for the patient, even if it has absolutely no economic returns for the gynecologist. However, this understanding has not yet been adopted by the community-based gynecologist. The elite group present at the Scottsdale conference recognized the value of global uterine ischemia (caused by UAE) as virtually eliminating a recurrence of fibroids. They also acknowledged the beauty of a bloodless field using embolization as an adjunct to large fibroid surgery. It may take years for their experiences to be documented, presented and accepted by the community-based gynecologist.

Olaf Istre, MD, PhD, of Ulleval University Hospital (Oslo, Norway), gave a presentation titled "Laparoscopic Occlusion of Uterine Arteries compared to UAE." He compared menstrual bleeding, uterine and fibroid size and symptom relief between 24 patients who had UAE and 22 patients who had their uterine arteries laparoscopically ligated. He found no significant differences in any of the measurements between the two groups with the exception of post-operative pain. Those patients who had ligation had significantly less pain post-operatively than those who underwent UAE. He concluded by stating that laparoscopic ligation of the uterine arteries for relief of symptomatic fibroids had the advantages of 1) the gynecologist can take care of the patient himself. 2) the gynecologist can diagnose and treat other pathologies at the same time, and 3) there is no need for special equipment other than standard laparoscopic instruments.

It is anticipated that some of the gynecologists at this meeting (early adopters) will start performing laparoscopic uterine artery ligation once there is a little more data available. It appears that any opportunity for an interventional radiologist to receive a referral for a UFE from a gynecologist not directly from the patient will occur during these next two years before widespread adoption of a procedure that gynecologists can perform. Although it was evident at this meeting that members of the AAGL were referring patients to an IR for a UFE, it would be this same group that would immediately start performing their own UFE-like procedures, or ligations, given the data to support it.

Manufacturers of interventional radiology products have jumped onto this market opportunity (see Table 6), creating specialized catheters for uterine artery delivery of embolic products. Biosphere Medical (Rockland, Massachusetts) was the first to gain specific FDA approval for uterine fibroid embolization. AngioDynamics (Queensbury, New York) and
Cook (Bloomington, Indiana) have PVA embolic agents that are being used for UFE, and in Japan and other Far Eastern countries, cut-up Gelfoam is used for the same purpose. Although Biosphere is actively marketing to gynecologists and interventional radiologists, generic PVA still maintains the lion's share of the UFE market.