Need for Mature Evidence to Validate HIFU

February 1, 2008

The use of high-intensity focused ultrasound (HIFU) as a method for ablation of a localized tumor growth is not new. Several attempts have been made to apply the principles of HIFU to the treatment of pelvic, brain, and gastrointestinal tumors. However, only in the past decade has our understanding of the basic principles of HIFU allowed us to further exploit its application as a radical and truly noninvasive, intent-to-treat, ablative method for treating organ-confined prostate cancer. Prostate cancer remains an elusive disease, with many questions surrounding its natural history and the selection of appropriate patients for treatment yet to be answered. HIFU may play a crucial role in our search for an efficacious and safe primary treatment for localized prostate cancer. Its noninvasive and unlimited repeatability potential is appealing and unique; however, long-term results from controlled studies are needed before we embrace this new technology. Furthermore, a better understanding of HIFU's clinical limitations is vital before this treatment modality can be recommended to patients who are not involved in well-designed clinical studies. This review summarizes current knowledge about the basic principles of HIFU and its reported efficacy and morbidity in clinical series published since 2000.

The authors provide an excellent review on high-intensity focused ultrasound (HIFU) technology and present an update on the latest efficacy and safety data relating to the treatment of prostate cancer. HIFU for prostate cancer appears to be highly reproducible with a very short learning curve compared to other minimally invasive surgical techniques (reference 24 in the article). These features, combined with potential repeatability and the "noninvasive" character of this ablative technique make it is easy to see why this technology is gaining publicity.

Complications of the Procedure

The reputedly short learning curve needs to be confirmed in other series. Indeed, that attribute may be questionable when one considers the associated morbidities reported in this review. Including only series from later than 2003, up to 22% of patients undergoing primary HIFU for localized prostate cancer may require a second procedure for completion. Erectile dysfunction rates ranging from 13% to 57% and bladder outlet obstruction in up to 22% have been reported depending on the series. Incontinence rates have improved in recent years, with grade II incontinence reported at 0.4% to 3% since 2004. Delayed-onset complications have not been an issue and, as with other modalities, some complications do resolve over time, with reports of initial incontinence rates after HIFU of 50% at 3 months improving to 7% at 12 months.[1]

The publicity surrounding HIFU has been growing and, encouragingly, more peer review and clinical trials have been evident. This trend will hopefully allow a methodical review of the technology and provide our patients with solid evidence-based information rather than what has been available before.

Objectives Not Yet Achieved

The objective of new technologies is to provide a therapy with equal or greater efficacy than the existing standard, while decreasing morbidity, invasiveness, and cost. These objectives have not yet been reached for HIFU. Morbidity has improved with modifications in recent series, but HIFU continues to have a significant stricture and fistula rate compared with radical prostatectomy or radiotherapy. To decrease morbidity, the additional procedures of transurethral resection of the prostate (TURP) and/or suprapubic tube placement have increased the invasiveness of HIFU therapy, requiring a 2- to 5-day hospital stay.

As such, it would be misleading to market HIFU therapy to physicians and patients as a noninvasive therapy for prostate cancer. Due to the prolonged natural course of prostate cancer, efficacy data will, unfortunately, take a significant amount of time to evaluate, especially in terms of cancer-specific survival. Gelet's results using HIFU as a salvage therapy (reference 33 in the article) are similar to those of salvage cryotherapy in terms of both short-term efficacy and complications.[2] Thus, the initial role of HIFU in treating prostate cancer will likely be as a salvage option for failed radiotherapy.

Conclusions

The technical challenges of HIFU are many, including the consideration of prostate gland size, intensity level, and frequency, balancing image resolution with depth of penetration, movement detection, and visually directed vs predetermined algorithm-based protocols.[2] As with cryotherapy, these difficulties will no doubt improve with time, and in the future, HIFU may have a well defined role in the treatment of prostate cancer. Until that time, however, physicians should proceed with caution and not be swayed by marketing or public pressures to advance the use of HIFU for prostate cancer before it is appropriately validated by mature evidence.

 

-Thomas E. Keane, MD
-Gary W. Bong, MD

References:

1. Ficarra V, Antoniolli SZ, Novara G, et al: Short term outcome after high intensity focused ultrasound in the treatment of patients with high risk prostate cancer. BJU Int 98:1193-1198, 2006.

2. Mohamed I, Ahmed S, Kastner C, et al: Salvage cryotherapy for recurrent prostate cancer after radiation failure: A prospective case series of the first 100 patients. BJU Int 100:760-764, 2007.