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Emerging Role of HIFU as a Noninvasive Ablative Method to Treat Localized Prostate Cancer

Emerging Role of HIFU as a Noninvasive Ablative Method to Treat Localized 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.

Prostate cancer remains the second most common cause of cancer-related mortality in the United States.[1] Although many treatments (eg, radical prostatectomy and radiation therapy) have been used to try and eradicate this disease, these options are still associated with significant morbidity. The goal of developing minimally invasive ablative techniques is to achieve tumor control with the least impact on quality of life.

The use of high-intensity focused ultrasound (HIFU) has been investigated as a minimally invasive ablative technology. HIFU uses single-focus ultrasound transducers that are moved mechanically to generate thermal damage and coagulative necrosis in the target tissue. This method is gaining rapid clinical acceptance among urologists and patients, due in part to its minimally invasive character, single-session treatment, minimal anesthesia, and perceived short recovery period and quick return to daily activity. The potential clinical efficacy and progression-free survival benefit of HIFU have not yet been thoroughly investigated, and long-term evidence of disease control is lacking. The main advantage of HIFU over other minimally invasive modalities for treatment of localized prostate cancer (eg, cryotherapy) is its truly noninvasive nature, ie, the fact that there is no need for percutaneous needle insertion.

HIFU has been used with variable success in the targeted ablation of malignant growths in several other organs.[2-4] This review summarizes information about the current status and understanding of the emerging use of HIFU for the local treatment of prostate cancer. It will include a critical analysis of the published HIFU clinical safety and efficacy trials, future trends for its clinical use, and the challenges facing its widespread application.

HIFU Principles and Challenges

HIFU involves the generation of an extracorporal ultrasound wave that is focused on a particular coordinate within the prostate gland. It generates enough energy at the target point to totally destroy the intended tissue. The practical use of focused ultrasound energy for neurologic therapeutic purposes was first suggested in the 1960s.[5] However, it was not until the 1990s that HIFU became a clinically acceptable ablation modality, primarily due to advances in three-dimensional imaging and precision targeting technology, which paved the way for its wider use.

A crucial characteristic of focused ultrasound energy is its ability to generate a highly confined lesion in the target tissue. The area of demarcation is so clearly marked that the temperature is not cytotoxic outside of this region. The "trackless" nature of the HIFU is unique because the energy source is placed some distance from the target area and does not require the use of radiation (Figure 1).[6]

It is hypothesized that HIFU achieves its cytotoxic effect by two distinct mechanisms: thermal and acoustic cavitation. A target temperature of 55°C held for at least 1 second appears to be the threshold beyond which irreversible coagulative necrosis and tissue death is achieved.[7] Acoustic cavitation (AC) refers to the ability of ultrasonic waves to form small cavities within the target tissue, a process known as acoustically induced cavity nucleation, which is medium-dependent. Additional ultrasonic excitation leads to volumetric pulsation of these cavities, also referred to as bubbles. AC plays a crucial role in augmenting thermal deposition efficiency during HIFU treatment, allowing higher focal destruction at the target point, while minimizing damage to the intervening path, and thereby reducing the potential for collateral damage. Since AC directly correlates with the heating process, it is currently being investigated as a potentially noninvasive method for monitoring treatment efficacy by registering the broadband noise emissions during the bubble-collapse process.[8]

In spite of significant advances in imaging in the past decade, several aspects of applying HIFU to the treatment of prostate cancer remain challenging. Adaptive focusing due to breathing and body movement remains the most challenging aspect of wide application of this technology.[9] The "piecemeal" nature of an ablation process in which the volume of lesion destroyed at any given time is small (ie, 1–3 mm in width and 5–20 mm in height)[10] makes it difficult to achieve complete and homogeneous ablation of the entire gland. In addition, suboptimal prostate ablation can result from the uneven heat tolerance reported in some tumor cells and the influence of local perfusion on heat distribution.[10] Attempts to utilize dynamic magnetic resonance imaging for the evaluation of regional prostate blood flow may refine and contribute to ultimately achieving more complete treatment.[11]

There are currently two ultrasound-guided transrectal HIFU devices for the treatment of prostate cancer: the Ablatherm (EDAP-TMS, Lyon, France) and the more recent Sonablate 500 (Focus Surgery, Indianapolis). Although these devices are approved in Europe and the Far East, their use is still investigational in the United States; phase III trials are underway to assess the safety and efficacy of HIFU. Although both devices utilize HIFU "trackless" principles, they have some important differences.[12] The Ablatherm, which utilizes fixed-power profiles and a single multifrequency probe tip, requires a preoperative transurethral resection of the prostate (TURP). The Sonablate 500, on the other hand, has operator-defined power settings and uses multiple transducers with varying focal lengths within the probe tip. The target destruction lesion is smaller with the Sonablate 500 than with the Ablatherm, which makes further manipulation of the probe necessary during planning.


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