Early Impressions of High-Intensity Focused Ultrasound for Prostate Cancer
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.
This well-written review article provides a very balanced report on high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer. The authors briefly describe the technology behind HIFU and some technical aspects of the procedure. They also provide a comprehensive review of ongoing clinical trials and previously published reports using HIFU.
The take-home message can be summarized as follows: HIFU seems to be moderately effective in treating localized prostate cancer, at least in the short term. Given the lack of long-term follow-up, HIFU cannot be recommended as primary therapy outside a clinical trial.
PSA Issues
Many of the published reports used neoadjuvant hormonal therapy, making it difficult to understand the prostate-specific antigen (PSA) results. A PSA nadir of < 0.5 ng/mL seems obtainable, and the use of the American Society for Therapeutic Radiology and Oncology (ASTRO) definition for tumor recurrence (three consecutive rises) seems reasonable. However, if HIFU truly destroys the prostate tissue, then the PSA should stay below 0.2 ng/mL. If portions of the prostate are treated subtherapeutically-thus supporting the use of the ASTRO definition of tumor recurrence-then prostate cancer could be untreated, bringing into question the efficacy of the treatment itself.
The reason why the PSA may rise after radiation therapy to the prostate is that radiation is more deadly to actively growing tumor than to normal tissue, and some patients will have a rising PSA due to the presence of benign tissue. HIFU destroys tissue using thermal energy, resulting in coagulative necrosis, and may also use acoustical energy. Therefore, there should be no normal prostate tissue in the zone of treatment.
Risks of Treatment
HIFU appears to be most effective in the treatment of small prostates. The need for a transurethral resection of the prostate (TURP) prior to HIFU is problematic and highlights the need for better technology to allow a deeper focal point. The side-effect profile of HIFU seems similar to cryotherapy or radiation seed implants. All three therapies can result in impotency, incontinence, and, rarely, fistulas. These complications occur due to heat, radiation, or cooling of the neurovascular bundles and urinary sphincter. If the entire prostate is to be treated, these structures are at risk-especially the neurovascular bundles.
The studies to date have not reported patient-defined incontinence and impotency results, making it diffcult to assess the true risk of HIFU. One side effect that seems specific to HIFU is sloughing of the treated prostate tissue. This is a significant problem resulting in urinary retention in most patients, although the long-term retention rate is low. Ongoing clinical trials should elucidate the frequency and severity of these complications.
Role of HIFU?
With these mixed results, it is unclear what HIFU will add to the currently established treatments of cryotherapy and radiation seed implants. It may well be the ability to perform truly focal therapy of the prostate. Cryotherapy needs to treat at least one-half of the prostate due to the ice ball formation, and the physics of radiation seed implantation makes it difficult to treat less than the entire prostate. HIFU has the ability to treat focal lesions accurately and hopefully effectively. The focal point of HIFU is very accurate, and in the appropriate patient may provide treatment to isolated prostate cancer without the morbidity that can occur by treating the entire gland. Clinical trials are needed to answer this question.
-David P. Wood, MD
