A US Food and Drug Administration (FDA) advisory panel voted yesterday not to recommend approval of a high-focus ultrasound technology to treat low-risk prostate cancer with less erectile dysfunction.
The technology, Ablatherm Integrated Imaging High Intensity Focused Ultrasound (HIFU), has been used in other countries in 40,000 patients for 15 years. It would be the first device of its kind to be approved in the United States.
But members of the Gastroenterology and Urology Panel of the FDA's Medical Devices Advisory Committee voiced a range of concerns about lack of data available from the technology sponsor's research results that were presented as part of its US premarket approval (PMA) application. HIFU is marketed in Europe by EDAP TMS, a French company operating in the United States as EDAP Technology.
The company is seeking premarket approval for HIFU as indicated for primary treatment of individuals with low-risk, localized prostate cancer.
In the end, a majority of panel members voted no to the question regarding a reasonable assurance that the treatment is safe. Panel members voted unanimously against reasonable assurance that it is effective.
HIFU is a robotic technology that consists of a treatment module that connects a control console to an endorectal probe device. After a patient is anesthetized, aurologist robotically controls the probe for insertion into the rectum, and the device delivers ultrasonic energy to a focused portion of the prostate.
High-intensity waves from an ultrasound imaging transducer in the probe generates intensive heat (85° - 95° C) and causes ablation of cancerous tissue while preserving the apex, sphincter, and rectum, with a lower rate of erectile dysfunction.
A rocky regulatory path developed almost from the start, however, for HIFU in the United States. A nonrandomized trial intended to be a pivotal study that began in 2006 to test HIFU against cryotherapy terminated in 2010 because of the company's inability to enroll enough patients, particularly for cryotherapy.
EDAP then conducted a meta-analysis of HIFU and cryotherapy results in the medical literature, plus a review of comparisons of a European HIFU registry with surgery in the US Veterans Administration study Prostate Cancer Intervention vs Observation Trial (PIVOT).
EDAP presenters at the hearing said the "body of evidence" supports the approval of HIFU in the United States. They said that the benefits of a noninvasive, localized therapy with precise energy delivery outweigh the risks for urinary obstructive morbidity and that side effects from HIFU treatment are "not dissimilar" to those of other prostate cancer treatments, including radiation therapy.
FDA presenters, however, went through EDAP's submission documents point by point, citing deficiencies, such as lack of information and potential safety concerns, including a 28% cumulative positive biopsy rate 2 years after HIFU treatment among individuals in the nonrandomized trial.
Regarding the lack of information, Johathon P. Jarow, MD, of the FDA's Office of Hematology and Oncology Products, said, "Absence of evidence is not the same as evidence of absence," and that it was not clear whether HIFU treatment is better than doing nothing for the low-risk patients.
The treatment does have its supporters, though. In the public hearing portion of the meeting, Pascal Rischmann, MD, professor and chair of urology, andrology, and renal transplant at Université Paul Sabatier in Toulouse, France, said that the treatment is safe and effective, that it preserves erectile function in more than 90% of patients through nerve sparing, and that it is cost- effective. He said he has used HIFU in more than 350 patients between 2006 and 2014.
Prostate cancer survivors also recommended approval during the public hearing.
Inderbir Gill, MD, chair of the University of Southern California, Los Angeles, Institute of Urology, and a monitor of the HIFU trial, told panel members that HIFU is certaintly not perfect but that all ablation technologies have similar biopsy rates.
"It's about patient choice," he said. He pointed out that HIFU has a track record of 40,000 patients during a 15-year period and that it has never been suspended or taken off the market.
But the FDA officials maintained that the benefit of HIFU is unclear and that the risk is substantial, although they acknowledged that EDAP's efforts had been constrained by practical difficulties associated with conducting trials for prostate cancer.
Stephen R. Kraus, MD, of the University of Texas Health Science Center in San Antonio and a temporary voting member, said he was concerned about the "murkiness" of the data, or "trying to use other trials to make up for the lack of recruitment. Murkiness is the absolute reason we need a controlled trial."
Consumer representative Mildred D. Fennal, PhD, RN, of the International Nurses Education Consortium in Tallahassee, Florida, said, "If anything, it sounds like they're trying to save all the work that's been done" and that maybe they should have reorganized early on and tried something else.
The advisory committee members have disclosed no relevant financial relationships.
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