Why HIFU Fails

Prostate cancer remains "public enemy number one" as men age. It is commonly stated that if men live long enough, we will all get prostate cancer. Put another way, if we live to be 100 years old, 100% of men will have contracted prostate cancer. Epidemiologically, it is estimated in excess of 230,000 men will get prostate cancer in 2011. This amounts to a new case of prostate cancer diagnosed every 3 minutes. According to the Surveillance, Epidemiology, and End Results (SEER)Data from the National Cancer Institute (NCI),more than 500,000 men will contract prostate cancer yearly by the year 2020. Clearly prostate cancer is epidemic, if not pandemic while representing one of the most unpredictable, yet potentially deadly, diseases men face.

“Multi-Parametric Prostate MRI Scan Predicts and Confirms the Presence of Prostate Cancer"

Once the diagnosis of prostate cancer has been made by a concordance of diagnostic techniques including: Prostate Specific Antigen (PSA),digital rectal examination (DRE)and a multi-parametric prostate Magnetic Resonance Imaging scan (with or without spectroscopy), the decision making process for treatment is expedited without undue risk to the patient for 'needle tracking'. In centers of excellence like the Diagnostic Center for Disease"? in Sarasota, Florida, biopsies are discouraged based on the aforementioned 'needle tracking' tied to an unacceptable cancer recurrence rate by 7-10 years posttreatment. Based upon the ability of MRI to localize a cancer, no more than 6 targeted biopsies are ever necessary (assuming the patient accepts the risks germane to biopsy) to find the most aggressive prostate cancers that pose the greatest risk to men. It is now common knowledge that 50-60% of prostate cancers diagnosed can be treated conservatively as they are associated with a Gleason 6 pathologic grade. What this means for the future is that the Urologist or Radiation Oncologist will be inclined to treat fewer cancers more aggressively with something other than Active Surveillance or Chronic Disease Management (COM), once the facts are universally understood. Assuming organ confinement of a cancer (validated by an MRIscan), a PSA value of less than 10.0 ng/rnl and an absence of digital rectal findings in association with a Gleason Score of 6 (3+3), an individual currently qualifies as a surgical candidate to the Urologist or Radiation Oncologist, who tries to make the case for cancer cure. While many of these patients would be excellent candidates for a CDM protocol, the majority of men with this clinical presentation of cancer (at the urging of their doctor) will often times choose a definitive form of cancer treatment, like a radical prostatectomy or radiation, rather than treat the disease conservatively. Lost in all of this is the fact that 30-56% of all prostate cancers diagnosed are over-treated. In 2011, the primary list of "definitive treatments" include: Robotic Prostatectomy, Prostatectomy without the robot, Radiation Seed therapy (Brachytherapy), Intensity Modulated Radiation Therapy (IMRT),Cryosurgery and Proton Beam therapy. While there are variations in the application of the techniques mentioned, there is one glaring omission! High Intensity Focused Ultrasound (HIFU), while available outside of the USAfor more than 15 years is not yet FDA approved and, therefore, not on the list of reimbursable treatments available in the USA! The prolonged delay in approval of this therapy is an unconscionable mystery when it is realized that HIFU is approved for uterine fibroids, (a benign disease) in women. Complicating the controversy further, HIFU is the most patient friendly treatment for organ confined prostate cancer in the world.

"HIFUis an Effective Therapy but as with any Cancer Treatment, Patient Selection is Critical to the Outcome"

Specifically, a study evaluating High Intensity Focused Ultrasound in Radiation failure patients is currently in a Phase III Trial format under the auspices of the FDA. Therefore, approval of HIFU (Ablatherm or Sonablate 500 technologies) in the USAis not anticipated until at least 2012 or 2013. 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 cure rates upwards of 80-87% at more than 5 years. The most significant obstacle is that men must agree to leave the country to receive this novel, if not quintessential prostate cancer treatment. The majority of men with the diagnosis of prostate cancer will make their treatment decision based on multiple reasons including their personal extensive research, excellence in side effect profile, cost, entitlement, family pressure, gut opinion, fear, venue of operation, insurance reimbursement, ease of application, time necessary to rehabilitate, speaking with friends and various other educational tools. Without question and assuming that money is not a determining factor in making a
decision, the best first choice in any disease treatment will always be the form of therapy that expeditiously allows a man to get back to living life to its fullest within the shortest amount of time while minimizing morbidity like incontinence and sexual dysfunction. The procedure that ranks number one for men, who don't have to depend on their insurance coverage to pay for their health care, 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 energy (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 definitive invasion of the Seminal Vesicles as determined by the MRI scan, the focused energy emanating from the treating transducer will treat the prostate tissue methodically with pinpoint accuracy allowing a block of cells of varying size to melt under intense heat measured at 70-90 degrees Centigrade. While no procedure is perfect, HIFU predictably ensures that if appropriate energy is delivered to the tissue, prostate cancer cells and benign cells that encounter the thermal energy will die. Equally appealing beyond a scalpel-less outpatient procedure is that the operation typically takes approximately 2 to 4 hours to complete (dependent on the technology chosen with Ablatherm typically taking 2 hours), as well as the ability to walk away with urinary continence and sexual capability. This is a reality for the majority of carefully selected patients.

"SexualPotency is maintained by Design as the Neurovascular Bundles are identified prior to initiating 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 understand the location of the neurovascular bundles that enable 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 acoustically generated thermal energy. The ability to treat the prostate with virtually no disruption of the prostate capsule avoids unnecessary spillage of cancer cells that is common to radical prostatectomy and Brachytherapy. 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 of many years, 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 that commonly occurs with radical prostatectomy and radiation therapy. As skilled surgeons, we must be able to accept that not all men with prostate cancer will be viable candidates for HIFU for a variety of reasons and, therefore, must be encouraged to treat their disease in some alternative manner.

"Why HIFU Fails to Cure Prostate Cancer"

So what clinical prostate characteristics preclude the success of the HIFU procedure? In a few words, prostate size, stones, and density of tissue i as these three anatomic observations represent the three most critical issues to be considered to assure the HIFU procedure to be performed effectively, assuming organ confinement of the cancer and an absence of obvious cancer into the Seminal Vesicles as noted preferentially by a preoperative MRI scan. Relevant to prostate size, there is an expectation for the gland to be treated, to be no larger than 30-40 grams or cubic centimeters. Ablatherm, a truly robotic procedure favors smaller prostate size while the Sonablate 500 technology can accommodate larger prostates. Prostate stones on the other hand, are equally problematic to both technologies. Calcification or stones are believed to be formed in the prostate tissue in association with prostate inflammation, a phenomenon common to all prostates that note a PSAvalue of greater than 1.0 ng/rnl, There is a concern that stones or calcification prevent the focused energy emitted from the transducer from getting beyond a calcified acoustic barrier to the tissue on the other side; thereby, 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. This statement has been validated as correct! 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 should not be greater than 4.0 centimeters (40 millimeters) ideally, consistent with the maximum distance the focused ultrasound beam must travel from the treating transducer to the prostate limit, anteriorly. This distance must be less when the Ablatherm technology is utilized. Tissue density would also be a factor that jeopardizes the success of the procedure if the thermal energy cannot penetrate effectively in all regions. Additionally, if cystic structures are encountered there is a possibility of a 'heat sink' effect. Heat sink in this instance is the dissipation ofthermal 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 be routinely evaluated by the implementation of the Gray scale ultrasound and Color Flow Doppler Ultrasound during the pre-treatment evaluation. The success with HIFUrelies 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.

"MRI can validate whether Prostate Cells are Alive or Dead"

Beyond an expectation for success with every procedure performed, HIFUfailure is objectively validated by a PSAvalue of greater than 0.2 ng/rnl and identification of live tissue on a MRI scan. Alternatively, a random needle biopsy, replete with the threat of spreading residual cancer cells beyond the prostate capsule, remains an option but unacceptable in my opinion. 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 PSAtesting 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 HIFUand why it will alter the treatment landscape once approved, are invited to visit our website at www.PanAmHIFU.com or 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 your clinical history.

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