More Questions About High-Intensity Focused Ultrasound
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.
Historically, the treatment of men with clinically localized prostate cancer consisted of radical prostatectomy or some form of radiation therapy. The disease control and side-effect profiles of these modalities have been widely studied and are well known.[1,2] More recently, the medical community has properly become interested in evaluating less invasive, ablative approaches as therapy for prostate cancer. Cryoablation has been used since the 1980s, and as this review shows, high-intensity focused ultrasound (HIFU) has more recently been studied. These ablative approaches hold the prospect of eradicating the disease while allowing the patient to quickly regain his preceding quality of life.[3]
This review of the current status of HIFU as a treatment option for clinically localized prostate cancer shows the strengths and limitations of this approach. While rates of short-term disease control (prostate-specific antigen stabilization and negative biopsy postablation) look promising (60%–80% for most studies at 6–77 months), one must acknowledge that these are not the ideal endpoints, as both are well known to be falsely indicative of disease control for many patients. As the authors mention, longer follow-up of men treated with this approach is mandatory before definitive conclusions about its role in the management of prostate cancer can be made.
While the data regarding "whole" prostate ablation as a treatment for prostate cancer matures, there is one tantalizing prospect that can be studied in the meantime. Perhaps HIFU, and other ablative approaches such as cryoablation and vascular targeted photodynamic therapy,[4] can be used for focal ablation of small-volume prostate cancers. Theoretically, these modalities are well suited to focal ablation as they are noninvasive and can predictably ablate specifically targeted regions of the prostate with minimal morbidity. Since currently many prostate cancers are proven to be of small volume at the time of diagnosis and radical prostatectomy,[5] many men may potentially be candidates for such an approach.
Treatment Planning
As we embark on evaluating focal ablation, what is missing are imaging tools and/or biopsy strategies that reliably inform clinicians of the location, size, and characteristics of a given prostate cancer. Magnetic resonance imaging (MRI) and its various methods (spectroscopy, dynamic-contrast enhancement, diffusion-weighted imaging) have been used to localize and estimate tumor volume of biopsy-identified tumors, albeit with marginal success.[6]
More promising are novel biopsy strategies that use template guidance and three-dimensional planning. A recent consensus conference on the focal treatment of prostate cancer[3] addressed the need for prostate biopsy strategies that provide more information about the prostate cancer and thereby can help optimize clinical decision-making. One such biopsy strategy uses transperineal "brachytherapy" templates to sample the prostate at 5-mm intervals. This approach results in 1 to 2 cores per gram of prostate and usually is done under anesthesia in an outpatient facility.[7] A less intrusive and equally promising strategy is the transrectal, office-based TargetScan approach.[8] Like the transperineal approach, this technique provides the precise location of each biopsy core and is performed in the office under local anesthesia.
Both of these template-guided, mapping techniques seem preferable to the current standard approach to prostate biopsy, wherein cores are randomly arrayed and, if they discover prostate cancer, often provide very limited information about tumor location, size, and other characteristics such as Gleason score.[9] Template-guided approaches seem to minimize the likelihood of missing cancer, provide better information about tumor size and Gleason score, and when cancer is discovered in a given biopsy core whose location is exactly known, may allow targeted treatments such as ablation to eradicate that specific region of the prostate.
Further Questions
This review of HIFU ablation of the prostate should serve as food for thought for clinicians struggling to improve the care of men with prostate cancer. Can ablation, together with better biopsy or imaging strategies, fundamentally change our approach to this common disease? Should ablation be combined with other approaches such as intralesional injections? We do not have the answers to these questions yet, but we now have a solid foundation upon which to develop new strategies.
-Ted A. Skolarus, MD
-Gerald L. Andriole, MD
References:
1. Schraudenbach P, Bermejo CE: Management of the complications of radical prostatectomy. Curr Urol Rep 8:197-202, 2007.
2. Loeb S, Nadler RB: Management of the complications of external beam radiotherapy and brachytherapy. Curr Urol Rep 7:200-208, 2006.
3. Bostwick DG, Onik G (eds): Proceedings of the Celebration, Florida Conference on Focal Treatment of Prostatic Carcinoma. Urology 70(6; suppl 1):S1-S44, 2007.
4. Trachtenberg J, Bogaards A, Weersink RA, et al: Vascular targeted photodynamic therapy with palladium-bacteriopheophorbide photosensitizer for recurrent prostate cancer following definitive radiation therapy: Assessment of safety and treatment response. J Urol 178:1974-1979 (incl discussion), 2007.
5. Mouraviev V, Mayes JM, Sun L, et al: Prostate cancer laterality as a rationale of focal ablative therapy for the treatment of clinically localized prostate cancer. Cancer 110:906-910, 2007.
6. Hricak H, Choyke PL, Eberhardt SC, et al: Imaging prostate cancer: A multidisciplinary perspective. Radiology 243:28-53, 2007.
7. Barzell WE, Meiamed MR: Appropriate patient selection in the focal treatment of prostate cancer: The role of transperineal 3-dimensional pathologic mapping of the prostate-A 4-year experience. Urology 70(6; suppl 1):S27-S35, 2007.
8. Andriole GL, Bullock TL, Belani JS, et al: Is there a better way to biopsy the prostate? Prospects for a novel transrectal systematic biopsy approach. Urology 70(6; suppl 1):S22-S26, 2007.
9. Anast JW, Andriole GL, Bismar T, et al: Relating biopsy and clinical variables to radical prostatectomy findings: Can insignificant and advanced prostate cancer be predicted in a screening population? Urology 64:544-550, 2004.
