Why HIFU Fails

“HIFU is an Effective Therapy but as with any Cancer Treatment, Patient Selection is Critical to the Outcome”

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A comparative study of High Intensity Focused Ultrasound to Cryosurgery, currently in a phase lll Trial under the auspices of the Food and Drug Administration, is not expected to result in approval of HIFU (Sonablate 500) in the USA until at least 2010 or 2011. Presently men, who choose HIFU, are able to make a judgment as to the relevance of this form of therapy based upon European and Japanese data which boasts an 85-90% rate for cure at more than 5 years. The most significant obstacle is that men and the women, who support them, must commit to leaving the country to receive this novel, if not quintessential prostate cancer treatment. The majority of men with the diagnosis of prostate cancer will have their treatment decision impacted based on multiple reasons including their personal extensive research, side effects, cost, entitlement, family pressure, gut opinion, fear, venue of operation, insurance
reimbursement, ease of application, time to rehabilitate, speaking with friends and various other educational tools. Without question and assuming that money does not get in the way of making a decision, the best first choice will always be the form of therapy that expeditiously allows a man to get back to living life within the shortest amount of time with all of his faculties intact.

The procedure that ranks number one for men, who don’t have to depend on their insurance coverage to pay for their healthcare, is High Intensity Focused Ultrasound (HIFU). The most compelling reason for this decision is the need for men to have the best percentage chance of remaining sexually potent and continent of urine and bowel function. HIFU is a procedure that uses acoustic sound waves to generate a thermal energy that is delivered with unparalleled precision to the prostate. Assuming there was no risk for extracapsular extension of disease or invasion of the Seminal Vesicles as defined by the 3.0 T MRI- Spectroscopy scan, the focused energy emanating from the treating transducer will treat the prostate tissue methodically with pinpoint accuracy allowing a block of cells measuring 3x3x12 mm (about the size of a grain of rice) to melt under intense heat measured at 70-90 degrees Centigrade. While no procedure is perfect, HIFU predictably ensures that if the appropriate energy is delivered to the tissue, prostate cancer cells and benign cells that encounter the thermal energy will die. Equally appealing beyond a scalpeless outpatient procedure that typically takes approximately 2.5 to 3.5 hours to complete, is the ability to walk
away with the urinary sphincter intact and sexual abilities commonly experienced the night of the procedure. This is a reality for the majority of carefully selected patients.

“Sexual Potency is Maintained by Design as the Neurovascular Bundles are Mapped Out of the Treatment Plan”

The ability to visualize in real time the location of the sphincter mechanism that allows a man to remain dry and free from urine leakage and map out the neurovascular bundles that feed the process of erectile function assures the vast majority of men with organ confined disease that functional social skills have been additionally protected from the acoustic heat wave. The ability to treat the prostate with virtually no disruption of the capsule avoids unnecessary spillage of cancer cells that is common to radical prostatectomy. Equally important is the ability to avoid rectal injury common to radiation delivered by IMRT, Brachytherapy with or without External Beam or Proton Beam therapy. Unlike cryosurgery, an equally destructive form of ablative therapy, the nerves, arteries and veins associated with the neurovascular bundle are proactively spared from trauma allowing erectile ability to remain intact. Despite all of the fanfare associated with HIFU, there are a significant number of failures nonetheless. To date, there is not a HIFU treating physician who has not experienced failure. As I previously stated, no therapy is perfect. So when and why does HIFU fail? As a practicing HIFU Physician, it is my experienced opinion that HIFU fails when we try to apply the technology to all patients rather than patients who qualify. In other words, to achieve the level of success with HIFU (or any procedure for that matter); patient selection is critical to the outcome. This is consistent with the application of any technical skill intended to cure prostate cancer. Therefore, we must not use the one size fits all mentality with HIFU as often times occurs with radical prostatectomy. As skilled surgeons, we must be able to accept that all men with prostate cancer will not be viable candidates for HIFU for a variety of reasons, and therefore, must encourage them to treat their disease with an alternative therapy.

“Why HIFU Fails to Cure Prostate Cancer”

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So what characteristics do we look for that will ensure the success of the HIFU procedure? In two words, size and stones; as these two anatomic observations represent the two most critical issues allowing for the HIFU procedure to be performed and be effective, assuming organ confinement of the cancer and an absence of cancer into the Seminal Vesicles as noted preferentially by a preoperative 3.0 T MRI-Spectroscopy scan. Relevant to prostate size, there is an expectation for the gland to be treated to be less than 40 grams or cubic centimeters with a preference for 35 grams or less. Prostate stones on the other hand, are equally problematic while believed to be formed in the prostate tissue in association with prostate inflammation, a phenomenon common to all prostates that note a PSA value of greater than 1.0 ng/ml. There is a concern that stones or calcification prevent the focused energy from getting beyond a calcified acoustic barrier to the tissue on the other side, absorbed by the stones, or worse; reflected back toward the rectal wall. While rectal wall injury is not common with HIFU, we always anticipate what may occur and prepare a plan to prevent it. It has been my experience that calcification (prostate stones) that fail to generate an acoustical shadow are not likely to alter the delivery of energy in any meaningful way. The most common location for prostate calcification is along the tract of the urethra (urine tube) as it passes through the prostate from the bladder as well as at the junction of the Peripheral zone and the Transition zone. Regarding the prostate size, the anterior to posterior diameter cannot be greater than 4.5 centimeters (45 millimeters), consistent with the maximum distance the focused ultrasound beam must travel from the treating transducer to the tissue. Tissue density would also be a factor that jeopardizes the success of the procedure as well as the possibility of a heat sink effect. Heat sink in this instance is the dissipation of thermal energy by a cluster of blood vessels (vascularity) or cystic structures that prevent a killing temperature from being delivered to the targeted tissue. A determination of vascularity, calcification, cysts and prostate dimensions can routinely be evaluated by the implementation of the Gray scale ultrasound and Color Flow Doppler Ultrasound during the pre-treatment evaluation.

The success with HIFU relies on the fact that effective energy can be delivered to the Peripheral zone where 70% of cancers live. Unfortunately, 30% of prostate cancers are located in the Transition or Central zones, making this area a tougher target to hit when this area is compromised by calcified tissue. This becomes more significant as the sophisticated consumer understands that upwards of 65% of prostate cancer is multifocal and multi-zonal, establishing the possibility that treatment failure may become a reality. It is the under-educated patient who becomes enamored and swept away by a cancer treatment process that allows him to hit a golf ball within 24 hours of a major technical procedure who may overlook the critical clinical points of due diligence that may compromise the entirety of the prostate ablative procedure, noting the objective of HIFU currently is to treat the entire gland. Beyond an expectation for success with every procedure performed, HIFU failure is objectively validated by a PSA value of greater than 0.2 ng/ml and identification of live tissue on a 3.0 Tesla MRI-Spectroscopy scan. Alternatively, a random needle biopsy, replete with the threat of spreading residual cancer cells beyond the prostate capsule, remains an unacceptable option. An absence of metabolites on Spectroscopy is tantamount with an absence of live cells and consistent with an EKG when the beat is gone; flat lined with no evidence of disease or living prostate tissue. “Spectroscopy Validates Whether Prostate Cells are Alive or Dead” While prostate disease in general and prostate cancer specifically continues to enjoy expanded press coverage, men will improve their chances of being diagnosed with less disease earlier by having PSA testing beginning at age 30 as I commonly suggest. This generation of men will have the opportunity to consider focal therapy that will be performed in concert with Magnetic Resonance Imaging technology to isolate the lesion in question as well as guide the delivery of thermal energy to a fraction of the prostate, while retaining healthy functional tissue. To be able to deliver thermal energy to a patient’s prostate in an outpatient setting over a lunch hour will become a very appealing concept to an upwardly mobile and
educated society.

Men interested in learning more about the excitement of HIFU and why it will alter the treatment landscape once approved, are invited to contact the Diagnostic Center for Disease™ in Sarasota, Florida at 1-877-766-8400 to visit with me personally on a
conference call whereby we can discuss the particulars of the clinical history.
References:

1. Yoon S, Wang W, Osunkoya A, Lane Z, Partin A, and Epstein J: Residual tumor potentially left behind after local ablation therapy in prostate adenocarcinoma. Journal of Urology 2008; 179: 2203-2206.
2. Villars A, McNeal JE, Freiha FS, and Stamey TA: Multiple cancers in the prostate. Morphological features of clinically recognized versus incidental tumors. Cancer 1992; 70: 2313
3. Truskinovsky AM, Sanderson H, and Epstein JI: Characterization of minute adenocarcinomas of prostate at radical prostatectomy. Urology 2004; 64: 733.
4. Epstein JI, Walsh PC, Carmichael M and Brendler CB: Pathologic and clinical findings to predict tumor extent of non-palpable (stage T1c) prostate cancer. JAMA 1994; 721: 368.

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