By: Dan Sperling, MD

In October, 2015 the U.S. Food and Drug Administration (FDA) approved the first high intensity focused ultrasound (HIFU) device for ablating prostate tumors (Sonablate 450®, SonaCare Medical, U.S.A.)  A month later, the FDA approved a second device for the same purpose (Ablatherm®, EDAP, France). The FDA pointed to the fact that the manufacturers’ equipment had demonstrated reasonable safety. In an explanation of the decision, Jarow and Baxley wrote for the AUA News , “The short-term data on PSA, prostate volume and prostate biopsy findings could support a tool type of indication (ablation of the prostate) and the FDA approved marketing of these HIFU devices as a means to promote further evolution of the technology and foster further evidence generation.”[i]

HIFU is a noninvasive invasive image-guided outpatient procedure that focuses the energy of ultrasound waves onto a small area of tissue. The sonic energy passes harmlessly through other tissues toward the target; when the waves converge, they generate high heat that ablates (destroys) tissue. The technology has evolved and now includes features that track thermal changes in real time. Coupled with advanced ultrasound imaging and computer software, it is now possible to map the ablation in such a way that HIFU’s side effect profile is relatively favorable compared with prostatectomy, making it an attractive choice. However, it is not appropriate for patients with large prostates, or glands that have calcifications that can block the sonic energy from its target.

For a decade, HIFU has been in use to treat prostate cancer in many other countries including Europe, Japan, Canada, China, Mexico and others. U.S. patients who were qualified for the treatment had to travel outside the U.S. to Canada, Mexico, Germany or certain Caribbean locations. Thus, the FDA’s approval was welcomed by physicians and patients alike.

As with all prostate cancer treatments, the goal of HIFU treatment to achieve effective cancer control (no recurrence) while minimizing the risk of side effects. While there are a few long term studies on HIFU, the most recent studies tend to report short- to mid-term results. It is difficult to obtain apples-to-apples results, but here are data drawn from four very recent papers:

Whole gland HIFU

1. Rouget et al. (2016)[ii] provided an analysis of cancer control and side effects of 191 patients with localized prostate cancer over eight years (mean follow-up 55.5±22.7 months). The Phoenix criteria for biochemical recurrence were used to assess oncologic control. Using the d’Amico risk classification, the authors reported biochemical survival free rates at 5 years of 87.5% (low risk PCa), 69% (medium risk) and 39% (high risk). For patients whose PSA nadir was less than or equal to 0.3ng/mL, 86% of them were relapse free at 5 years, but for those whose PSA nadir was greater than 0.3ng/mL only 48% were relapse free. According to the investigators, “The urinary and sexual impairment was significant but 78.1% of the patients were dry at the end of the study.”
2. Uchida et al. (2009)[iii] likewise published an 8-year study showing biochemical disease-free rates similar to those of the Rouget paper: 84% (low risk PCa), 64% (medium risk) and 45% (high risk).  The authors note, “Postoperative erectile dysfunction was noted in 33 out of 114 (28.9%) patients who were preoperatively potent.

 Focal HIFU

1. van Velthoven et al (2016)[iv] tracked cancer control, continence and potency of 50 patients with unilateral low-risk prostate cancer (on only one side) who had a HIFU hemiablation (considered a focal treatment since only that half of the gland was treated). Suspicion of treatment failure was defined as biochemical recurrence (rising PSA after nadir). All patients were included in the results with a median follow-up of 39.5 months. Using the Phoenix criteria for biochemical control, 36% of patient experienced biochemical recurrence. At 5 years, their data showed 93% metastases-free survival, 100% cancer-specific survival and 87% overall survival rates. Regarding side effects, 94% were completely continent (no pads), and 80% were able to achieve erection sufficient for intercourse. The authors concluded that for qualified patients, HIFU “affords mid-term promising functional and oncological outcomes.”
2. Yap et al. (2015)[v] reported on post-treatment sexual function after focal HIFU, using data combined from three prospective trials comprising a total of 118 men with localized prostate cancer. Patients’ sexual performance was tracked at intervals of 1, 3, 6, 9 and 12 months post-HIFU using self-report questionnaires (International Index of Erectile Function or IIEF-5) and use of PDE5-inhibitors (e.g. Viagra). Although sexual scores showed a significant drop from baseline at 1 month, average sexual scores had returned to almost baseline levels by 12 months after HIFU. The authors found that the primary predictor of post-HIFU sexual function was pretreatment performance, and concluded that focal HIFU “confers a high probability of maintaining erectile function.”

As HIFU technology continues to advance, and more U.S. urologists become proficient in its use, patients will have another alternative to prostatectomy and radiation available to them. For now, the limitations of gland size and calcifications will exclude certain men from considering HIFU. Patients are encouraged to research the advantages, cancer control, and side effect profile of HIFU just as they do for any other treatment.

[i] Jonathan Jarow, MD and John Baxley, MD. “FDA Approves HIFU as a Prostate Ablation Tool.” AUA News, Feb. 2016, p. 15.

[ii] Rouget B, Capon G, Bernhard JC, Robert G et al. Eight years of experience with HIFU for prostate cancer: Oncological and functional results.[Article in French] Prog Urol. 2016 Jan;26(1):50-7. doi: 10.1016/j.purol.2015.09.010.

[iii] Uchida T, Shoji S, Nakano M, Hongo S et al. “Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: Eight-year experience.” Int J Urol. 2009 Nov;16 (11): 881-86. DOI: 10.1111/j.1442-2042.2009.02389.x

[iv] van Velthoven R, Aoun F, Marcelis Q, Albisinni S et al. A prospective clinical trial of HIFU hemiablation for clinically localized prostate cancer. Prostate Cancer Prostatic Dis. 2016 Mar;19(1):79-83. doi: 10.1038/pcan.2015.55.

[v] Yap T, Ahmed HU, Hindley RG, Guillaumier S et al. The effects of focal therapy for prostate cancer on sexual function: a combined analysis of three prospective trials. Eur Urol. 2015 Oct 30. pii: S0302-2838(15)01013-1. doi: 10.1016/j.eururo.2015.10.030.