Many efforts have been made to try to find less invasive ways to destroy fibroids. Most of the less invasive techniques that have been developed involve either thermoablative therapies or image-guided therapy or both.
Thermoablative therapies use heat or cold to destroy tissue. This approach has been used in the treatment of other diseases, including freezing the cervix to treat abnormal Pap smears and using a variety of probes to heat lesions in organs such as the liver or the kidneys.
Image-guided therapy involves the use of some type of imaging to guide the procedure, rather than a traditional surgical (visualize and touch) approach. The imaging can be provided by conventional X-rays, ultrasound, or more sophisticated methods, such as computed tomography (CT) or magnetic resonance imaging (MRI) guidance. Some of these techniques have been around for many years, such as the use of dye and X-rays to examine the uterus and the fallopian tubes when a hysterosalpingogram is done as a part of a fertility workup. Many are relatively new, such as CT guidance used to drain abscesses deep in the body without open surgery.
One of the earliest approaches for uterine fibroids using a thermoablative technique utilized a probe to deliver heat during a conventional surgical approach. Myolysis (as discussed here: laparoscopic myomectomy and myolysis for fibroids) was first introduced using a laser; in further studies bipolar needles were used to destroy the fibroid tissue. Both of these devices were used at the time of laparoscopy to destroy a subserosal or intramural fibroid without literally excising it, as would be done at the time of a laparoscopic myomectomy. The advantage of this approach is that less finely tuned surgical skills were needed than for one that utilized laparoscopic suturing. This circumstance would make a laparoscopic approach available for more women undergoing surgery, but it still required a surgical approach and general anesthesia.
Myolysis was never widely accepted, likely for several reasons. First of all, from a physician’s point of view, the procedure was rather tedious, and even a small fibroid needed multiple placements of the probe to destroy it. Concerns were also raised about the risk of adhesions or scar tissue that would form on the surface after this approach. There were also procedures done using a freezing probe (cryomyolysis) in a similar manner at the time of surgery. This technique did not gain wide acceptance, probably for similar reasons.
The next wave in these minimally invasive therapies came when MRI monitoring could be used for control of therapy. This was an important development, since there are special MRI parameters that can gauge temperature. The problem with surgical control of thermoablative therapies is that the eye has to gauge when the correct temperature is reached and the procedure is complete. This is as difficult to do as gauging the temperature of a pot sitting on the stove by looking at it. Clearly, you can get some clues by direct vision, such as when steam is emitted from the pot, but an accurate visual gauge is impossible.
Accurate gauging of the temperature created during a thermoablative therapy is critical. If the temperature is too high, normal tissue is likely to be damaged or destroyed. This can present safety problems and can lead to injury of other tissue, in addition to the previously discussed risk of adhesions. However, if the peak temperature is too low, the tissue may not be destroyed, and, in essence, there is no effective treatment. This is a particular issue for fibroid treatments because fibroids vary widely in their composition and the same amount of energy does not produce the same target temperature or amount of tissue destruction in every fibroid.
The first image-guided thermoablative therapy for fibroids was conducted in a small series of patients who underwent cryomyolysis during laparoscopy performed in a special MRI machine that allowed surgical procedures to be carried out while the patient was in the MRI magnet. However this MRI-guided cryomyolysis required both the traditional surgical incisions and treatment within an MRI machine and also has not been widely adopted. Not only was this approach more costly and just as invasive, but many traditional surgical instruments are metal and can’t be used in an MRI machine.
A later approach, percutaneous laser ablation, involved inserting laser fibers through the skin of the abdominal wall and into the targeted fibroid. Only local anesthesia was used during this procedure; it was used to numb the skin where the fibers were inserted. After the fibers were in the fibroid, treatment took place while the woman was inside a standard MRI machine so that the temperature could be gauged. Although this laser ablation approach was limited to fibroids in the front of the uterus, the approach was much less invasive and allowed women to be treated as outpatients; follow-up at one year demonstrated shrinkage of the treated fibroid and a decrease in menstrual blood loss following treatment.
Using focused ultrasound instead of the laser fibers led to the first noninvasive thermoablative therapy, MRI-guided focused ultrasound surgery (MRgFUS). This is the only thermoablative therapy for uterine fibroids that has received the approval of the US Food and Drug Administration (FDA).
Focused ultrasound surgery (FUS) and high intensity focused ultra-sound (HIFU) are two terms that describe a similar process. Just like a magnifying glass can focus light so that heat can be produced at a specific point, multiple ultrasound waves can pass through the skin at different points and only at the focal point where they all meet will they deliver enough energy to cause tissue destruction. By using many different bursts of these focused ultrasound waves, a fibroid can be destroyed. Each individual burst of FUS energy is termed a sonication (sonic = sound).
The MRI guidance allows the temperature of the treated fibroid to be measured during each sonication to maximize complete treat-ment and minimize injury to surrounding structures. In addition, the MRI provides a view of all the important structures around the uterus (like the bowel, bladder, and pelvic nerves) and thus helps to avoid injury to these structures.
During treatment a woman is lying on her stomach so that her fibroid is up against the source of the ultrasound energy, which is in the bed of the MRI. Generally an intravenous line is inserted so the woman can have some pain medication and relaxing drugs similar to those used in UAE. A catheter is used to empty her bladder so the fibroid does not move as the bladder fills during the treatment; the catheter also eliminates the need for the woman to use the bathroom, which would require stopping the treatment. The woman is also asked to shave the top part of her pubic hair prior to the procedure, since this decreases skin burns caused by tiny air bubbles trapped at the base of the hairs. Most programs also use elastic stockings to keep the blood from pooling in the legs while the woman is lying still for treatment, preventing deep vein thromboses (DVTs) and pulmonary embolisms (PEs), similar to the procedures used during surgical approaches.
Treatment currently takes place over about 3 hours. Because there are no incisions and the sedation is light, women go home after treatment. Most women go back to work in 1 or 2 days, with 4 days the longest reported time out of work in the studies.
In contrast to UAE, women having FUS treatment typically do not have the pain and fever of postembolization syndrome after treatment. There appears to be a difference between the ischemic necrosis caused when the blood supply to the uterus is interrupted following UAE and the coagulative necrosis caused by FUS, in which the proteins are immediately denatured (like the changes that occur when cooking an egg). With ischemic necrosis, cells are broken open as they die and release agents that cause fever; this process does not occur with coagulative necrosis. Although initially it was not clear whether there was a difference between the two types of necrosis or just the amount of tissue treated, it is now clear there is a difference in the type of necrosis.
There appear to be parallels between UAE and FUS, however, in that both provide at least some of their short-term symptom relief without necessarily causing shrinkage. To provide a variation on the analogy used in this article: uterine artery embolization, having a lead ball sitting on your bladder is more uncomfortable than having a cotton ball of the same size in the same place.
Early studies have shown that between 70 and 80 percent of women have at least a 10-point improvement in symptoms at 6 months as determined by the Symptom Severity Score (SSS) of the Uterine Fibroid Symptoms Quality of Life (UFS-QOL) questionnaire. This measure is important for the studies of FUS and is likely to be used in assessment of more fibroid treatments in the future.
Quality of life is more difficult to measure than the amount of shrinkage of a fibroid achieved by ultrasound treatment, but it is more important. How a disease affects your life and work is what matters. Many standard questionnaires look at health-related quality of life. A good summary of the field is found at www.cdc.gov/hrqol.
The UFS-QOL is the only questionnaire that specifically asks questions about both the bleeding symptoms and the bulk-related symptoms experienced by women with uterine fibroids. There are several different parts of the UFS-QOL; the most widely used is the Symptom Severity Score. The SSS uses 8 questions to understand how much the symptoms of fibroids affect a woman’s quality of life. It is scored on a 100-point scale; normal women usually score around 20 points, and women with fibroids score on average 40 points.13 Thus, when the studies were designed to test focused ultrasound treatment (termed the pivotal trial), a 10-point improvement appeared to be a meaningful measure of fibroid symptom improvement. Women in the focused ultrasound studies who improved only 8 points would be considered treatment failures. This is a higher bar than that used in most other fibroid studies including those of UAE, in which even 1 point of improvement could count as improvement or the target could be a 10 percent improvement (4 points if the baseline is 40 points). “Success rates” between different studies cannot be compared if they are not measuring the same thing.
In fact, a 10-point improvement proved to be a conservative estimate of improvement in the initial study of FUS. Women enrolled in this trial had a baseline SSS of over 60 before treatment and on average had more than 20 points of improvement 6 months following treatment. Modest shrinkage of the treated fibroid was also seen at 6 months, on average 13 percent, with treatment of an average of 10 percent of the total amount of fibroid(s) in the uterus.
One of the issues that need to be assessed in early reports of new technologies is whether the drug or device is FDA-approved for use in treating another disease or condition (an indication for treatment). If there is no approved indication, all treatments will take place as a part of clinical trials regulated by the FDA because the drug or device is “investigational.” However, in the United States (but not in most other countries), individual physicians are allowed to use approved agents for treatments of other indications if there is sound medical evidence that they may be safe and effective.