The decision about which prostate cancer treatment to choose depends on many variables, including your PSA level, the stage and grade of your cancer, your age and overall health status. Standard treatments for early-stage, localized prostate cancer include surgery (radical prostatectomy), external beam radiation therapy (EBRT) and brachytherapy (radiation seed implants). Since these generally offer similar outcomes in terms of cancer control, the choice may often come down to personal preference, taking into account side effects and quality of life. Another option for patients who have life expectancy of less than five to 10 years or whose likelihood of disease progression is small may be active surveillance (i.e. choosing not to have any treatment until evidence of higher-risk cancer appears).
Newer treatments include cryosurgery (freezing of the prostate to eliminate the cancer) and high-intensity focused ultrasound (HIFU).
HIFU is now being used extensively to treat localized prostate cancer in Europe, Russia, Japan and other Asian countries. Sanctioned by Health Canada in 2005, it’s currently available in private centres in Ontario, Québec and Manitoba. In the United States, HIFU is still under investigation in clinical trials and hasn’t received the stamp of approval by the Food and Drug Administration (FDA). Research is ongoing to determine HIFU’s long-term effectiveness as well as any lasting side effects.
How HIFU works
HIFU is a highly precise, minimally invasive, image-guided procedure. A probe (transducer) inserted in the rectum focuses high-frequency sound (ultrasound) waves into the prostate, destroying targeted cancer cells by rapidly raising the temperature of the tissue (up to almost 90 degrees Celsius in a few seconds). Clean (non-ionizing) energy ultrasound beams are pulsed systematically into very small zones mapped out in the prostate, until the whole gland has been treated. Cold water circulates around the transducer to cool the rectum and minimize rectal wall heating. HIFU destroys cells at the focal point without harming healthy surrounding tissue.
HIFU is an outpatient procedure that takes two to three hours (depending on the size of the prostate). Spinal or epidural anesthesia is administered with sedation to keep the patient from shifting position during the operation, and most men experience no pain. A catheter is placed in the bladder through a small abdominal incision, and remains in place for two to three weeks or until the patient can urinate on his own. Most men can resume a normal diet and routine almost immediately.
Who’s eligible?
HIFU may be an option for men with low- or intermediate-risk disease who aren’t interested in or candidates for active surveillance. The cancer must not have spread outside the prostate gland.
Low risk (favourable)
- PSA less than or equal to 10 ng/mL
- Stage T1c–T2a: no nodules felt on DRE, or small nodule in less than half of one side of the prostate
- Gleason score: 6 (3+3)
Intermediate risk
- PSA 10–20 ng/mL
- Stage T2b: larger nodule confined to one lobe
- Gleason score: 7 (3+4 or 4+3)
HIFU may also be used as salvage therapy for patients whose cancer recurs locally after radiation therapy, or as repeat therapy.
Controversies
Like other treatments for prostate cancer, HIFU has both advantages and disadvantages (see HIFU pros and cons). The procedure has been practised for over two decades, but reports on the overall risks and benefits are conflicting. Many practitioners claim excellent results in terms of cancer control with virtually no side effects; others report high failure rates necessitating repeat treatments, with significant morbidity of almost 50%, including incontinence, impotence and uretro-rectal fistula. Lesser risks involve urinary obstruction, infections and catheter-associated issues.
The discrepancies between these findings are likely the result of variations in patient selection, device sophistication, surgery experience and competence (learning curve). Earlier versions of the technology lack some of the more sophisticated safety and monitoring components, which may have contributed to some of the less favourable results. Differences may also be due to the difficulty in monitoring the exact effect of heating on the various components of the prostate and surrounding tissue.
To try to understand the true benefit of HIFU technology, cancer agencies in British Columbia and Ontario have commissioned studies to examine its effects on prostate cancer (see www.bccancer.bc.ca [search under “HIFU”]; http://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=47392). The most recent study suggested that HIFU should be considered an “investigational” treatment since it has never been subjected to standard clinical trials comparing it to conventional therapies. As such, it was not recommended as an alternative to conventional treatments of localized prostate cancer.
In a sense, however, all treatments for prostate cancer are “under investigation,” as researchers are still evaluating the outcome of even the most established therapies like surgery and radiation.
One proponent’s view
Dr. Laurence Klotz is Chief of Urology at the Sunnybrook Health Sciences Centre in Toronto, Ontario, and Professor of Surgery at the University of Toronto. He is one of the partners in Can-Am HIFU, a private clinic that offers HIFU therapy for localized prostate cancer with the Sonablate® 500 system. Can-Am HIFU (www.can-amhifu.ca) has a small ownership interest in Toronto HIFU LP.
Our Voice interviewed Dr. Klotz to learn about his experience with HIFU.
OV: Is HIFU considered an “experimental” therapy for prostate cancer?
LK: Over 20,000 patients have been treated (with both devices available on the market: Sonablate 500® and Ablatherm®) and we now have 10 or more years of follow-up. Its short-term outcome and efficacy are proven, although we still need more long-term data. I would say the therapy is now a well-established alternative to surgery or radiation.
OV: What is the main appeal of HIFU?
LK: Most people find HIFU appealing because it’s a minimally invasive therapy that doesn’t involve ionizing radiation. Some men are uneasy about radiation, for several reasons: 1) limited salvage options if radiation fails; 2) concern about secondary malignancies in the radiated field; 3) some people just don’t like radiation. Also, many men want to avoid surgery.
OV: How is HIFU used mainly?
LK: It’s used probably 90% as a primary treatment, as opposed to for recurrent cancer.
OV: What percent of patients have to undergo a second cancer treatment of any kind after HIFU?
LK: Between 10% and 20%, depending on the patient’s initial risk factors.
OV: What is the difference between the Sonablate 500 and Ablatherm devices?
LK: Both systems use the same principle, with some technical differences. The Ablatherm device has two transducers, one for imaging purposes and one for treatment. Sonablate uses one transducer for both. Ablatherm proponents argue that they get a better image, but on the other hand the transducer is larger, so it may be a little bit harder to get in, thus more traumatic. The size of the treatment zone is larger with the Ablatherm, so Sonablate advocates maintain they get a more precise zone of treatment because a smaller area is targeted with each application of energy. Ablatherm patients are treated in the left lateral position (lying on their side); Sonablate patients in the lithotomy position (stirrups).
Despite the differences, at this point the outcomes looks quite comparable. There’s more experience with the Ablatherm in Europe, and with the Sonablate in Japan and the US. It’s hard to compare results head-to-head, because of differences in patient selection and so on. To my mind, the similarities dramatically outweigh the differences. One important thing: Both systems require a skilled operator and should be used by physicians who have a fair bit of experience.
OV: What advances have been made in HIFU technology in recent years?
LK: The engineering is constantly being fine-tuned. One recent addition to the Sonablate 500 system is a software module called TCM (Tissue Change Monitoring), which shows in “real time” how much energy is being delivered, so you can adjust the amount of HIFU each area is getting. Another development is three-dimensional (3D) imaging, which allows better prostate visualization. Third is the use of advanced Doppler Ultrasound technology to identify important structures such as the sphincter muscle, neurovascular bundles (responsible for erectile function) and rectum, to minimize complications.
Finally, another important factor is that we now have 10-year follow-up on disease-free survival after HIFU for localized prostate cancer, from Japanese researchers who were the first to start doing this procedure with the Sonablate device.
Naturally, we’re seeing the best results with favourable-risk prostate cancer. Somewhere around 75% to 80% of HIFU patients achieve a PSA nadir (i.e. the lowest PSA reading) less than 0.5 ng/mL, and around 80% have negative biopsies. Overall, the success rate is around 80% for low-risk disease, and 70% for intermediate-risk disease. With radiation, it may take several years to reach the lowest point, because PSA continues to drop for two to three years. Also, PSA may “bounce” up for months to years after radiation. With HIFU, PSA drops almost immediately, meaning failure is observed much earlier than with radiation. Results appear comparable between HIFU and radiation, but it’s hard to compare them head-to-head.
OV: In your experience, how safe is HIFU?
LK: HIFU isn’t free of complications. The major side effect is scarring of the prostate, which can cause problems with urinating.
At least 10% of men need a second procedure
(i.e. cystoscopy and/or dilation) to open up
the prostatic urethra. This is, in most cases,
a one-time procedure done under local anesthetic that takes five to 10 minutes.
The incontinence rate is low but not zero. Out of about 80 cases I’ve done, only three of my patients have significant urinary incontinence. The effect on erectile dysfunction depends on how aggressively you treat. If you spare the area near the neurovascular bundles, which can be done readily, the ED rate is really quite low. If you treat aggressively for more advanced prostate cancer, the rate is higher.
Overall, in my experience, 80% of patients have a great result — few side effects, good voiding and no impact on their erectile function. The other 20% have some trouble, either scar tissue necessitating another procedure, or significant impact on their erectile function.
Again, HIFU involves a learning curve on the part of the practitioner. We’ve been doing HIFU at our Toronto clinic for four years now. In my case, my patients who have incontinence were all treated in our first year. Experience really does make a difference.
OV: What research is being done currently?
LK: There are two large clinical trials in the US: one comparing HIFU to cryosurgery and the other to brachytherapy. These are not strictly speaking randomized trials, but comparisons of similar patients at a HIFU centre with those treated at the other centres. In Canada, we’re collecting results from a prospective phase II trial to look at outcome and morbidity. Our early experience confirms that HIFU is effective and safe compared to standard treatments, but reiterates the need for further long-term studies.
We’ve also just launched a salvage study — a clinical trial with patients who have a positive biopsy a year or more after radiation. Currently, the radiation failure trial will take place in Toronto (see www.can-amhifu.ca) and Winnipeg, but other trial sites may be opening in Canada in the future.
OV: Do you foresee HIFU becoming an insured service?
LK: My guess is that we’re probably going to follow the American lead on this. HIFU hasn’t been approved yet in the US — they’re waiting for the results of two large prospective trials being done by the Cooperative Clinical Trials group. It’s interesting — it was an FDA decision to demand these trials for HIFU, whereas they didn’t require a trial like this for robotic surgery. So they’ve set a fairly high bar for HIFU.
My expectation is that HIFU will get approval. Once that happens and it has become widely available in the US, and presumably funded by insurers, then I think the pressure will be on to have it publicly funded here as well. But it may take a long time. Private insurance plans here don’t reimburse it either, but it is a tax-deductible medical expense.
OV: Are there any other important points people should keep in mind about HIFU?
LK: In my opinion, the future of treatment for low- to intermediate-risk prostate cancer is image-guided, minimally invasive therapy. It’s going to be some version of HIFU or perhaps MRI (magnetic resonance imaging)-guided ultrasound, which is a very hot area people are working on at the moment. HIFU is well established and, over time, the results should get even better due to more understanding of exactly how to use it and improvements in technology.
While HIFU is an appealing therapy for a lot of patients, I don’t think the advantages are so absolutely overwhelming that patients should “sell the family farm” to get it. In fact, I discourage patients from taking a major financial hit, because there are other treatments available that don’t cost the patient anything. But for eligible men for whom it is affordable, HIFU may offer some real advantages.
