In a Crowded Field, High-Intensity Focused Ultrasound Stakes a Claim

Scott Eggener, MD

The landscape for the patient with localized prostate cancer is filled with both new and exciting treatments. With better methods to screen, improved imaging scans to determine physical location and extent of cancer, and even active surveillance (AS), there are many options to consider.

Despite these advances, however, no consensus has emerged regarding the optimal treatment for the most common patient with prostate cancer: the man with clinically localized stage T1 to T2 disease with no regional lymph node or distant metastasis (T1 to T2N0-NxM0). Of the 234,460 men in the United States diagnosed with prostate cancer annually, 91% have localized disease, according to the American Urological Association (AUA).

“A substantial proportion of men who are diagnosed with prostate cancer can very safely and effectively just be monitored and don’t require any treatment,” said Scott Eggener, MD, associate professor of surgery and co-director, Prostate Cancer Program at the University of Chicago. Traditional treatments like radical prostatectomy or radiation are still the standards of care with the best known, long-term outcomes for cure, but there are adverse effects associated with each. He noted that whole gland treatment of prostate cancer carries a risk of incontinence and sexual dysfunction.

Appropriately selected patients who choose AS, monitoring of their cancer without immediate treatment, can expect excel-lent long-term results but may experience anxiety that stems from not treating a diagnosed cancer. The AUA notes that patients with lower-risk tumors (low Gleason score, PSA level, and clinical stage) could be candidates for this management strategy. Several studies have shown that patients with lower- grade, localized prostate cancer have an extremely low risk for metastatic progression within the first 10—15 years after the diagnosis, although approximately 30% to 50% of men will re-quire surgery or radiation at some point after initiating AS.

Parameters for surveillance is a discussion that needs to occur between the patient and his physician before this course of action is undertaken. Currently, providing evidence-based recommendations for when to intervene in patients with a long life expectancy are not possible since markers of disease progression are poorly validated. Most reports describe a clinical strategy that includes regular prostate-specific antigen (PSA) level measurement and digital rectal examination with a periodic repeat prostate biopsy along with an option of more active therapy if biochemical (increasing PSA) or histopathologic (in-creased tumor grade or volume) progression occur.

Focal therapy has been proposed in recent years as a means of filling the gap in the treatment spectrum between whole gland treatment and AS. Many believe that for patients with intermediate-risk disease, focal therapy is an attractive option for maximizing quality of life by avoiding the effects of whole gland radiation or surgery while alleviating the anxiety and uncertainty of AS by targeting and ablating the tissue that contains disease which may pose a real threat to the patient. Ablation of the entire prostate or targeted ablation of only the malignant parts of the prostate are possible by a variety of technologies, including cryoablation, radiofrequency, microwave, laser, vascular targeted, and electroporation devices. One new option in the United States is the use of focal therapy using high-intensity focused ultrasound (HIFU).

Enter HIFU

“There’s been a movement to consider more minimally invasive approaches, such as treating part of the prostate, rather than the entire prostate, which may lead to quicker recovery and fewer side effects but has not been established with long-term cancer-related outcomes,” said Eggener.Ultrasound energy is focused at a specific location in the prostate gland called the focal point. At the focal point, prostate tissue is heated to nearly 195°F (90°C). The tissue at the focal point is destroyed, but the surrounding tissue remains un-harmed. Because the technology uses ultrasound energy, not radiation, to destroy targeted tissue, the procedure can be repeated if necessary. The minimally invasive procedure can be used to ablate prostates up to 40 cm3 in volume without previously performing a transurethral resection of the prostate procedure.

Tissue analysis is conducted via radio frequency (RF). An RF signal is sent to a targeted ablation site prior to delivery of HI-FU and then another signal is sent after delivery of HIFU to the same site. The device calculates the change that took place and displays it on the screen. Tissue changes are quantified based on a comparison of RF ultrasound pulse-echo signals at each ablation site.

In addition, with the use of magnetic resonance (MR)-guided HIFU, the urologist can obtain an accurate anatomic depiction of the prostate gland and the tumor itself. This method also allows for a good depiction of thermoregulation in which the temperature of the tissue is monitored in real time. MR-guided HIFU has recently demonstrated promising results in the treatment of both benign and malignant tumors, said Alexander Copelan, MD, a radiologist at Beaumont Health and Oakland University William Beaumont School of Medicine.

“In prostate cancer, HIFU shows promise in very early prostate cancer and I think it’s an attractive option for patients who don’t want to undergo radical prostatectomy,” said Copelan.

HIFU has been used for treating malignancy in the kidney, liver, pancreas, and breast. In Europe, it has been widely used for whole gland therapy for prostate cancer. There are two major systems in use, the Ablatherm (EDAP TMS SA) and the Son-ablate (Focus Surgery Inc). The FDA granted regulatory approval to both the Sonablate and the Ablatherm devices via the 510 K pathway, approving the devices for prostate tissue ablation.

“HIFU offers a middle ground approach whereas the traditional therapies have been all-or-nothing: radical or passive,” says John C. Rewcastle, PhD, medical director at EDAP TMS. “With HIFU you have an accurate, minimally invasive ablation option that can be applied to the whole gland or focally.”

For the urology practice that is interested in investing in this technology, there is the cost of the equipment, the warranty, and the maintenance contract to consider, said Marc Oczachowski, chief executive officer of EDAP TMS. “Acquisition of a HIFU device does require a capital investment, but it is at significantly less than other robotic technologies.”

Rewcastle added that the technology is mobile—the bench that the patient rests upon can be wheeled around—as is the desk that houses the computer. Ambulatory centers that perform other scans could also incorporate HIFU technology. “Service providers are getting on board,” said Rewcastle, “Getting access to HIFU does not necessarily require purchase of the device.”

Training Required

Urologists see a lot of men who are appropriate candidates for AS and who are going to stay on AS. But they also see pa-tients with intermediate disease which is on the lower end of the spectrum. For those men, HIFU is a viable option. The other benefit of undergoing HIFU treatment is that further treatment options like surgery or radiation are not ruled out because the surrounding tissue receives minimal damage.As with any new technology, a rigorous and comprehensive training program should be undertaken by the urologist. “We’ve seen this in other settings, where low-volume, early adopters of technologies are not adequately trained and bad things can happen,” cautioned Eggener.

EDAP TMS has been operating in Europe for more than 20 years using the HIFU procedure, said Oczachowski. With active HIFU programs in over 50 countries, “we have perfected the training process to ensure reproducible outcomes in all these countries. We are very well versed in physician training,” he added.

The urology surgeon receives a HIFU training manual prior to visiting one of the qualified HIFU reference sites to observe a complete treatment process performed by a certified proctor treating his own patients. HIFU training materials include a training program, a training manual, a complete HIFU literature review, and a device user manual. In addition, nurses and operating room staff are provided with a dedicated HIFU training program supported by a specific documentation.

Over time, HIFU technology will likely become more prevalent in the United States, and “its attractiveness as a treatment option to patients who do not want to undergo surgery is evident,” said Copelan.

Eggener concurs but also emphasizes that vast majority of patients who are going to be good candidates for active surveillance do not require expensive interventions that have potential side effects. “But for the patient who might benefit from treatment, HIFU is going to be the new kid on the block on a long list of potential prostate cancer treatments,” he said.