Kate Johnson

May 08, 2016

SAN DIEGO — Since the approval of two high-intensity focused ultrasound (HIFU) devices last fall by the US Food and Drug Administration (FDA), the field of urology in the United States has been in limbo.

The technology — used in Australia, Canada, and Europe for the treatment of prostate cancer — was not approved for that indication in the United States because the device manufacturers were unable to demonstrate efficacy.

Instead, the approval of HIFU was simply for "prostate ablation," leaving a huge question mark for clinicians, patients, and insurers.

The FDA stopped short of telling clinicians how to practice medicine, saying that "clinicians, in consultation with their patients, should decide how best to use this tool," explained FDA spokesperson and urologist Charles Viviano, MD, PhD, during a plenary session here at the American Urological Association (AUA) 2016 Annual Meeting.

Has the FDA decision resulted in confusion? "Oh yeah," plenary moderator Michael Koch, MD, professor and chair of the Department of Urology at Indiana University in Indianapolis, told Medscape Medical News.

Is that a bad thing? Not at all, suggested Samir Taneja, MD, director of urologic oncology and the genitourinary oncology program at the NYU Cancer Institute in New York City, who moderated a case panel discussion during the plenary.

"I think it's a good thing," he told Medscape Medical News. "It's really critically important for our field to really rigorously study how it should be used."

The current HIFU landscape in the United States is like being given a car with no instructions on how to drive it, AUA secretary Manoj Monga, MD, from the Cleveland Clinic, previously told Medscape Medical News.

And although this plenary was aimed at providing some direction, it actually showed that there might be many starts and stops to come.

Fringe or Future?

"Learn from Australia and Canada. Do not make the same mistakes we have for whole-gland prostate treatment with HIFU," cautioned plenary speaker Nathan Lawrentschuk, MBBS, associate professor of urology the University of Melbourne, who has practiced in both countries, where the technology has been used for more than a decade.

"In my opinion, it is a fringe treatment used in patients on the fringe of mainstream medicine," he said.

In stark contrast, the 15- to 20-year experience with HIFU in Europe has been a big success, according to Christian G. Chaussy, MD, professor of urology at University of Regensburg, Germany, and clinical professor of urology at the Keck School of Medicine, University of Southern California, in Los Angeles.

The strategy of treating prostate cancer with HIFU might need "rethinking," said Dr Chaussy, who also presented during the plenary. "It's a hope for the United States; for the rest of the world, it is already reality."

Narrowing the Focus

But the reality of HIFU in the rest of the world is that its precise focus for the treatment of prostate cancer remains a matter of debate.

In the more than 80 peer-reviewed publications on HIFU, reporting on 65,000 treatments worldwide, HIFU is used for a mix of whole-gland treatment and focal therapy.

"Oncologic and functional outcomes of whole-gland ablation have been established. Outcomes of focal therapy have been shown to be durable. This could fill the gap between active surveillance and definitive radical therapy," according to Dr Chaussy.

But Dr Lawrentschuk pointed out that "large multicenter trials are lacking, there are different technologies and protocols, there is lack of consensus on ideal candidates, and there is a lack of follow-up biopsies, failure rates, and morbidity reporting."

Three recent European studies show cancer-free and metastases-free survival rates in the 90% range at 10 years, said Dr Chaussy (J Urol. 2013;190:702-710; BJU Int. 2013;112:322-329; Eur Urol. 2014;65:907-914).

But Canadian and Australian studies suggest high post-HIFU morbidity, including urinary incontinence and erectile dysfunction, said Dr Lawrentschuk.

Why Such Disparity?

"HIFU requires a huge amount of back-up, sophistication, and expertise," said panelist Mark Emberton, MD, a HIFU expert from University College Hospital in London, United Kingdom.

"You can't do anything that complex without building up experience. If you look at data from groups that have done four or five or six cases, you will get poor results. You need to look at data from the experts," he explained. "I think we're at the very early stage of the refinement and development of this technology. We look forward to the time when we can come over here and gain knowledge and experience from experts on this side of the Atlantic."

Middle Ground

The United States "may be on the cusp of a paradigm shift" when it comes to HIFU, according to Dr Koch, but in his opinion the shift would likely only be appropriate for localized disease. "I personally don't think it's the right treatment if you need your whole prostate treated."

Indeed, when whole-gland HIFU is compared with radical prostatectomy or radiation, "in terms of cancer outcomes, it's not as good; there are more short-term recurrences," agreed Dr Taneja.

But, for focal therapy "one could argue that HIFU comes at a very opportune time," he added. This focal therapy approach homes in on the index malignant lesion in the prostate gland and involves removal of only the affected part, not the whole gland, as in prostatectomy; for that reason, it has been likened to a "male lumpectomy."

"I do think HIFU is very promising for focal therapy. You're trying to reduce the risk of prostate cancer mortality, with minimal side effects, recognizing that you may not be eradicating the disease altogether — we may be leaving small amounts of low-grade tumor behind — but we don't think that's going to affect survival. That's a shift in thinking, and the dogmatic people in our field are going to have to take that leap."

"The fact is that over the past 5 to 10 years, we've treated a lot of men too aggressively," added Dr Koch, emphasizing the therapy should not be considered an alternative to active surveillance. "There needs to be a middle ground for people who have small, contained lesions," he said. "Some people will have recurrences [after HIFU] and have to get their prostate out, but if you can avoid having your prostate out for another 5 to 10 years, it's a big win."

"Those of us who are enthusiastic about focal therapy would say the right approach would be to use the right tool for the right tumor in the right patient. In that way, HIFU is a great addition to our armamentarium," said Dr Taneja.

Who Pays?

But the elephant in the room is payment.

Without FDA approval of HIFU for the treatment of prostate cancer, "most third-party payers probably won't pay for it," predicted Victor W. Nitti, MD, from the NYU Langone Medical Center, who is a spokesperson for the AUA.

"Patients are going to have to make decisions based on what urologists tell them, so urologists need to know as much as possible so they can advise their patients," he told Medscape Medical News.

But Dr Koch thinks the movement will be largely patient-driven.

"Many guys don't want their whole prostate out and they see this as a big win if it's reasonably effective in treating cancer," Dr Koch said. "One of the companies has been doing a lot of these offshore for cash, and there are a lot of people who want it."

Dr Viviano, Dr Koch, Dr Taneja, Dr Monga, Dr Chaussy, and Dr Nitti have disclosed no relevant financial relationships. Dr Lawrentschuk reports financial relationships with AstraZeneca, Astellas, Amgen, Tolmar, Ferring, and Janssen.

American Urological Association (AUA) 2016 Annual Meeting: Late-breaking plenary. Presented May 6, 2016.

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