Uterine fibroids, technically known as uterine leiomyomata, are non-cancerous tumours that arise in the walls of the uterus, either individually or in clusters. According to the US National Institute of Child Health and Human Development, at least 25% of women in the US suffer from these tumours, which account for more inpatient hospital days than AIDS, breast cancer, dementia, cirrhosis, prostate cancer or epilepsy. Some estimates suggest that as many as 77% of women have the condition, but may be unaware of it because they exhibit few or no symptoms.
Until recently, the main treatment for symptomatic uterine fibroids was invasive or minimally invasive surgery – drug therapy provides only short-term symptom relief. A hysterectomy (the surgical removal of the uterus) is the most common surgical procedure to treat uterine fibroids, and more than 200,000 women in the US undergo the operation each year. For patients who wish to have children in the future, a myomectomy (the surgical removal of the fibroid) is the preferred option. But the direct cost of these procedures is thought to be more than $1bn a year, and could be as high as $3bn. They are also associated with long recovery times of up to eight weeks.
In the 1980s, laparoscopic techniques began to emerge, followed in the 1990s by uterine artery embolisation. Although less invasive and expensive than hysterectomies or myomectomies, these methods still carry significant risks. Like its more invasive counterparts, laparoscopic surgery still requires full anaesthesia, and is not suitable for larger, multiple or deep fibroids. The dangers associated with uterine artery embolisation include radiation, premature menopause, serious infection, bleeding and the embolisation of tissue other than the fibroids; as a result, many patients opt to put up with the tumours, taking a ‘wait-and-see’ approach.
According to Dr Matthias Matzko, head of the department of clinical and interventional radiology at the Hospital of Dachau in Germany, this is no longer necessary as a new treatment option is coming to the fore: MR-guided focused ultrasound (MRgFUS).
MRgFUS is a non-invasive, outpatient surgical procedure that uses high-intensity focused ultrasound waves to ablate tissue in combination with MRI, which visualises the patient’s anatomy, maps the volume of fibroid tissue to be treated and monitors the temperature of the uterine tissue after heating. The thermoablative component of MRgFUS occurs when multiple sound waves from an ultrasound source pass through the skin and converge at a focal point in the target.
“I always tell my patients that the focused ultrasound is the knife and the MRI is the eye of the operator,” says Matzko, who is also head of the hospital’s FUS Centre. “The MRI offers you nearly real-time feedback of the structures you are treating inside the body, and the temperature they reach. This is extremely important in order to avoid side effects.”
The technology was first approved by the US Food and Drug Administration in 2004 for pre-menopausal women with symptomatic fibroids who had no desire for future fertility. But the labelling of the procedure was changed in 2009 to take into account the desire for future pregnancy. Although this is still not an absolute contraindication, it is generally accepted now that MRgFUS does not impair fertility.
The technique offers several advantages over the other treatment options: it is incisionless, there is no radiation involved, and anatomical and thermal MR images – updated in real-time throughout treatment – allow doctors to distinguish between treated and non-treated tissue.
Pioneers in precision
Dr Matzko has been working with the MRgFUS system at the Hospital of Dachau since the middle of 2008. In November 2010 his facility became the first clinical site in Europe to upgrade to the most up-to-date version of the technology, the ExAblate One. He’s currently collating the statistics for the first 20 patients to be treated with it – and the results are even better than with the first version of the system.
“When used with fibroids that are not too highly perfused, we managed nearly 100% ablation, which is a significant improvement on the old system which had an ablation rate of 65%-69%,” he notes. “Fibroids with an increased blood perfusion can also be treated with the new system. We’ve reached ablation rates that are comparable to the low-perfused myomas with the old system. There’s a possibility that we can treat 20% more patients than before with the same results.”
As well as increasing the number of patients who can be treated – and potentially doing so with zero side effects – the system has advantages for the doctors carrying out the treatment.
“It’s a much better user interface because we now have a real 3D-volume planner,” says Matzko.
“This means that, as a user or doctor, you only need to define the critical zones of the anatomy of the patient and the myoma volume to the system; after that, the system automatically calculates a treatment plan that takes everything into account. Everything you had to do manually, such as changing the ablation volume or adjusting the energy used, is done by the system now.”
The advancement of this technology has one important consequence: it could lead to the treatment of myomas before they start making trouble. At present, women are advised to wait until the fibroids start becoming problematic, whether that manifests in the form of strong bleeding, pain or the inability to become pregnant, before seeking treatment. Matzko sees focused ultrasound technology as a way of nipping the problems fibroids can cause in the bud.
Feedback from women who have undergone MRgFUS treatment at the Hospital of Dachau has been mostly positive, though this is largely because Matzko has a thorough pre-selection programme in place. “Every patient has to get an MRI beforehand,” he explains. “We then discuss their situation carefully. Are the myomas in the beam pathway? Can we reach all the tissue? Can we reach the areas of myoma tissue that are particularly problematic? If it is feasible, we still discuss other treatment opportunities with the patient. They can then decide whether to sign up or not.
“Patients with informed consent are much more motivated. Previously, they had no choice; now they have a choice of several therapy options – an operation, embolisation, focused ultrasound.”
However, a large number of women cannot be treated with MRgFUS. For example, those with cardiac pacemakers or other metallic devices that are contraindications to MRI cannot be considered, while women with a high body mass index may be excluded due to the difficulty of positioning within the bore of the MRI machine.
Extensive scars were a problem in the past: with the ExAblate One it is possible to treat women with extensive scars without ‘damaging’ scars. When pre-selection is carried out, MRgFUS has a comparable success rate to laparoscopic surgery, with 10% of patients requiring re-treatment. As such, most eligible patients opt for the focused ultrasound option.
“You don’t have any scars, you can leave the hospital two to three hours after treatment and the only thing the patient has to take into account is mild pain akin to menstrual cramps for one or two weeks,” Matzko adds.
Besides ablating uterine fibroids, the most up-to-date MRgFUS systems can be used to treat adenomyosis, a condition where endometrial cells spread into the uterine wall during a woman’s hormone cycle. “Until now, there was no option to treat this condition in an effective manner except hysterectomy,” says Matzko. “Now, focused ultrasound can be used to ablate the endometrial tissue in the uterine wall. We’ve had very good results with these patients; symptoms are generally gone one or two months after treatment.”
Moreover, the technology has been CE labelled to treat pain caused by bone metastases. Bone is the second most common site of metastatic spread, affecting 90% of patients with progressive breast cancer, and it is estimated that 100,000 people in Europe are diagnosed with bone metastases every year. The majority of these patients suffer with pain, so controlling and managing its symptoms are important goals in the healthcare community.
“The results are very promising, not only in terms of the significant reduction in the pain levels of the patients,” says Matzko. “It is now being shown that we can reach a local tumour control of bone metastases with MRgFUS. You can’t heal the patient – it is still a palliative option – but it’s very helpful because it means they don’t have to rely on harmful drugs or pain medication.”
A feasible field?
Despite the advantages associated with MRgFUS, the treatment is not in widespread use, something Matzko believes is largely down to reimbursement issues. “The reason we have been so successful at the Hospital of Dachau is because we managed to get contracts with the two biggest public insurance groups in Germany,” he remarks. “We are the only hospital to have achieved this. I think the therapy will become more common when there is a general possibility of reimbursement, but at the moment I think this is the reason that many hospitals are avoiding making investments in the technology.”
On top of this, many in the scientific community believe that more long-term research is needed to determine the safety and efficacy of the procedure. In a paper published in Ultrasound in Obstetrics and Gynaecology in 2009, Professor Wladyslaw Gedroyc of the MRI Unit at St Mary’s Hospital, Imperial College, London, argues that without effective randomised studies, this field will not progress as rapidly as it should. He is adamant that these need to be carried out in the next few years.
Looking further into the future, MRgFUS has the potential to be used to treat a range of other conditions, breast cancer among them. “Phase II clinical studies are being held in which patients are treated for breast cancer with focused ultrasound without an operation afterwards,” Matzko notes. “The same goes for peripheral prostate cancer. There are two sites – one in St Petersburg, Russia, and one in Singapore – that are producing very good results. Again, more studies need to be done to get this into the clinical routine.”
In the context of treating prostate cancer, the high-intensity focused ultrasound beam can be delivered with millimetre precision, destroying the cancerous tumour without damaging surrounding tissue, which is the cause of most complications. The use of real-time 3D MR thermometry provides accurate closed-loop monitoring of the treatment outcome and the ability to adjust the treatment according to specific patient physiology in real time.
Although Matzko has demonstrated excellent results with ExAblate One at the Hospital of Dachau, the treatment remains far from routine in the healthcare community. When further long-term research has been carried out and reimbursement issues have been rethought, however, this middle road between invasive surgery and drug therapy will likely be welcomed with a huge sigh of relief as a treatment for uterine fibroids.