and DIANA TUCKER
BB&T Contributing Editors

ORLANDO — The frenetic pace of innovation in the field of medical devices is well-known by all stakeholders in this industry. That was apparent at the mid-May gathering of the American Urological Association (AUA; Linthicum, Maryland) the largest worldwide meeting for this specialty.

The same holds true on the distaff side, as a Society of Gynecologic Surgeons (SGS; Germantown, Tennessee) postgraduate course on advanced gynecologic surgery held in Chicago late last year featured looks at new injectable solutions to female incontinence issues.

As in past years' AUA sessions, significant attention at the 2008 meeting was devoted to the myriad diagnostic and treatment modalities for prostate cancer, by far the most common cancer in men. According to the American Cancer Society (Atlanta), about 186,000 new cases of prostate cancer will be diagnosed in the U.S. this year.

About one in six American men will receive a diagnosis of prostate cancer during his lifetime, usually after age 60. This cancer will cause an estimated 29,000 deaths this year in the U.S., making it the second-leading cause of cancer death in men, exceeded only by lung cancer.

Since this cancer generally progresses quite slowly, about 15% of men newly diagnosed opt for "watchful waiting." However, for those that decide to seek an intervention, there are a plethora of choices currently available, with more on the horizon.

Various forms of radiation, such as external beam radiation therapy (EBRT), intensity modulated radiation therapy (IMRT) and brachytherapy and the long-time and conservative "gold standard"— surgical excision of the prostate (radical prostatectomy, or RP) — have long formed the backbone for treatment. Radiation and RP each accounts for around 40% of the prostate cancer treatment market, with cryoablation accounting for another 5% or so. (See Table 4 for a look at the current market for the different approaches to prostate cancer.)

However, newer technologies have in recent years begun to heavily impact the traditional modalities. For example, robotically-assisted RP, marketed aggressively and astutely by Intuitive Surgical (Sunnyvale, California) now accounts for at least half of the overall RP procedure market. In 2007, an estimated 45,000 to 50,000 robotic RP procedures were performed, surpassing the number of conventional RP surgeries for the first time.

Intuitive's booth at the AUA was consistently packed with urologists eager to learn more about the technology and how to incorporate it into their surgical practice.

Two new and intriguing technologies were displayed by their corporate sponsors for the first time at an AUA meeting. Accuray (also Sunnyvale), which several years ago pioneered the concept of highly-precise robotic radiosurgery for brain tumors and then broadened into other types of cancers, has in the past couple of years begun to market its technology for prostate cancer.

The company's CyberKnife, which has been installed in more than 130 sites worldwide, integrates modern imaging technology, intelligent robotics and high-dose radiation delivery, merged with complex algorithms to precisely target cancerous tumors.

The CyberKnife appears to well-suited to prostate cancer. Its advanced robotics allow it to track, detect and correct for unpredictable prostate movement during therapy, thus accurately destroying the cancer while surrounding nerves and healthy tissue are safely preserved.

Because of its sub-millimeter accuracy, CyberKnife radiation doses can be far higher than conventional radiation, with the upshot that it can accomplish tumor destruction in just five sessions vs. 40 sessions for EBRT or IMRT.

Compared to its longstanding successes in other cancers, its impact on the prostate cancer market is still modest. In the company's fiscal 2007, about 600 prostate cancers were treated with CyberKnife. Although Accuray has not disclosed its prostate cancer cases so far this fiscal year, this number could easily triple or quadruple. Conversely, in the last fiscal year, roughly 8,000 brain cancers were treated, with an additional 2,000 cases each for lung and spine cancer.

Clearly, in the technology-crowded prostate cancer treatment market, more clinical data will be required to validate the technology. Thus it is not surprising that the company is in the early stages of two key clinical trials.

The first trial will be treating early stage organ confined cancers and will compare the CyberKnife to HDR (high-dose rate) temporary brachytherapy. It will treat a total of 330 patients, who will then be followed for five years. The principal investigator is Don Fuller, MD, a radiation oncologist who founded the CyberKnife Centers of San Diego (San Diego) and is a strong proponent of the technology.

A second trial will enroll an additional 330 patients and also do a five-year follow-up. The principal investigator is Robert Meier, MD, a radiation oncologist from the Swedish Cancer Institute (Seattle). He also has had considerable experience with the CyberKnife in treating prostate cancer. This trial will compare CyberKnife to a homogeneous dose distribution in early-stage organ confined cancers.

At an even earlier stage of development is irreversible electroporation (IRE) technology that is being developed by the interventional radiology company AngioDynamics (Queensbury, New York). It provided some IRE information at its booth.

IRE energy is delivered through needles and image guidance very similar to existing ablative technologies (such as radio frequency or cryothermia) but instead of heating or freezing to kill the targeted tissue, it uses electrical fields to cause cell death. The powerful electrical field, which passes through an electrode array, causes permanent nanoscale defects or pores in the cell membranes. The permanently impaired cells are then removed through the body's natural immune system.

As compared to other ablation methods, it is highly selective and does not damage adjacent critical structures such as ducts and blood vessels

The technology was developed at the University of California, Berkeley and then licensed to a private company called Oncobionic. In October 2006, AngioDynamics signed an agreement to acquire Oncobionic, making an initial investment of $5 million and a commitment to pay an additional $20 million within two years, subject to successful human use of IRE.

In April, AngioDynamics reported that the first human clinical cases, treating prostate cancer, had been performed and that it was moving forward with its plans to complete the acquisition of Oncobionic. As per the agreement, an additional $10 million was paid, with two more payments of $5 million each scheduled within the next 18 months.

IRE has broad application within the field of cancer, but given the large number of cases occurring per year, the company has opted to begin with this area. Although six human cases have been performed to date, taking advantage of a 510(k) approval received in November 2006 for soft tissue ablation, AngioDynamics now will proceed with a prostate-specific clinical trial, first treating animals and then moving into human trials.

Although a full-scale market launch may be a few years away, this technology, in the words of Gary Onik, MD, the president of Oncobionic, shows "... promise to become the next generation of ablation technology."

Product news at AUA

• SRS Medical (Redmond, Washington) reported the "official" U.S. launch of its UroCuff CT 3000, a system designed for non-invasive diagnosis of male bladder function. The device was demonstrated at the AUA conference.

SRS makes equipment for urodynamics, the diagnostic procedures that are the standard of care for patients with lower urinary tract symptoms (LUTS).

"The UroCuff CT 3000 meets a longstanding need for accurate, non-invasive assessment," said CEO Kevin Connolly. "Many men who have been reluctant to undergo the catheterization necessary for conventional urodynamics can now be tested quickly and comfortably. We are proud to be part of such a significant advance in diagnostic technology."

This year, thousands of men over 50 who suffer from LUTS will undergo transurethral resection of the prostate (TURP). This procedure is not without risk, and up to 30% of patients see no change in symptoms following the operation, according to SRS. The UroCuff CT3000 is designed to help identify those patients that have good bladder contractility, yet suffer from Bladder Outlet Obstruction. This group of patients is known to demonstrate improvement following TURP, the company said.

The UroCuff CT3000 uses a method similar to that for blood pressure measurement. A penile cuff is fitted to the patient who is then asked to void into an integral uroflow instrument. An estimate of isovolumetric bladder pressure and a measurement of maximum flow rate are obtained to allow categorization into obstructed, not obstructed, or "diagnostically uncertain" groups.

Studies have shown that the 87% success rate for TURP in men classified as obstructed was similar to that achieved by invasive urodynamics in previous studies (79% to 93%), according to SRS. The company said more than 40 peer-reviewed publications now attest to the clinical use of the UroCuff CT3000.

The device was developed by scientists from the Freeman Hospital (Newcastle-Upon-Tyne, UK) and validated by the clinical team at Bristol Urology Institute (Bristol, UK). Mediplus, a manufacturer of disposables for urodynamics and other medical specialties, markets the product and SRS has been granted a sub-license for exclusive U.S. distribution and worldwide manufacturing.

• NDS Surgical Imaging (San Jose, California) reported availability of new visualization technologies for surgical and endoscopy suites, including a new Radiance 52" touch-screen display.

The company said it demonstrated an interactive, purpose-built Radiance 52" touch-screen combined with imaging informatics platforms designed to deliver customized clinical content to operating room staff and enhance surgical workflow. It also showcased an LED-backlit surgical display technology that is supposed to provide "superb" brightness designed specifically for endoscopic use.

New guidelines for cryotherapy

The AUA introduced clinical guidelines with best practice statements for prostate cryotherapy. The guidelines state that cryoablation is a treatment option for men with clinically confined prostate cancer of any grade and that salvage cryoablation is a treatment option in men who have failed radiation therapy.

Prostate cryotherapy uses extreme cold to freeze and destroy prostate cancer cells. This minimally invasive procedure is routinely and successfully performed on prostate cancer patients with varying disease stages as well as those who have failed radiation treatment.

Richard Babaian, MD, professor and senior medical director at the M.D. Anderson Physician Network (Houston), presented the new guidelines for cryotherapy for the treatment of localized prostate cancer at the plenary session of the annual meeting.

Injection therapy no longer just for the urethra

December is typically not the month to visit Chicago; however, gynecologic surgeons from around the country braved the snow and cold weather last December to learn the latest tried and true techniques in women's pelvic surgery.

The Society of Gynecologic Surgeons has a select member group of more than 250 physicians representing both private practice and academic faculty involved in teaching and the practice of advanced gynecologic surgery. As a society, those surgeons have the stated mission "to promote the highest standards for gynecologic surgical care for women in a safe, effective and ethical manner."

The topics discussed at the cold-weather gathering ranged from hysterectomy alternatives to fecal incontinence after childbirth, the three-day course presenting clinical experience and "how-to" instructions on the most recent developments in female pelvic health, including a focus on urinary incontinence, a condition that affects an estimated 25 million Americans.

To set the stage for the topic of female urinary incontinence, Linda Brubaker, MD, professor of female pelvic medicine and reconstructive surgery at Loyola University Medical Center (Maywood, Illinois), first reviewed a large survey performed at Kings Hospital (London) on incontinent women that begged the question: "What do women really want?" To which Brubaker replied, "We can deliver being perfectly dry, but then there will be trade-offs with side effects and complications."

This keystone survey explored the acceptability of symptoms versus the acceptability of treatments for female incontinence and found that incontinent women were not insistent on being totally dry, but rather were quite satisfied with a marked improvement in their daily life (see Table 5).

Overall, "less than 20% needed a complete cure and 43% would be satisfied with good improvement such that the symptoms no longer interfered with their life," Brubaker cited from the study. Her presentation, "Injectable Therapies," addressed both stress urinary incontinence and now also urge urinary incontinence.

She said, "It is important to understand what matters to the patient when offering them op-tions. Injection therapy is a reasonable option for some women as long as the alternatives, risks and complications are reviewed. A good diagnosis also is critical, since a reduced overall success with injection therapies has been shown in patients with mixed urinary incontinence."

Injectable therapies fit quite nicely into the parameters of patient acceptable treatments as determined from the survey discussed above. For stress urinary incontinence, bulking agents have been used for several years, especially for intrinsic sphincter deficiency, although only three are currently cleared by the FDA (see Table 6).

No longer are injections just for the urethra, as Allergan's (Irvine, California) Botulinum toxin A, although not cleared by the FDA for urge incontinence, is making a lot of patients happy. "Currently multiple clinical trials are underway and there is growing evidence of its efficacy that has been well documented in neuropathic populations," Brubaker said, "And thanks to Hollywood, patients are no longer afraid of it anymore."

Her experience has been that 60% of selected urge incontinent patients have had their symptoms adequately controlled. Not only does the Botulinum toxin A paralyze the muscles in the bladder, there seems to be evidence of neurologic changes as well, having to do with sensory input that triggers urge. Although the literature indicates only 10% of the patients experience transient retention, Brubaker's experience was slightly higher, so she requires all patients to be taught self-catheterization prior to receiving the "bladder botox."

The injections are well-tolerated under local and topical anesthesia in an office setting using either a rigid or flexible cystoscope. Lidocaine is placed in the bladder with xylocaine jelly in the urethra for patient comfort. Some 20 injections are painted on the posterior bladder wall in the detrusor muscle and the response seems to be durable at least six months, but the timing of repeat dosing is still unclear. Botox for the bladder could be emerging as a potentially powerful new therapy for urge incontinence.

Another innovative treatment that Brubaker has designed in collaboration with her patients is that of using oxybutrin PRN "as needed," instead of around the clock. Since 69% of women surveyed claimed that medication for life was not an acceptable treatment, and the known dryness side effects of oxybutrin are often not tolerated well,

Brubaker asks the appropriate patients to go on the drug for a month or so and "test drive" it — discovering if they truly need it around the clock, or if it works for them in eight-hour intervals, such as during a work day, or on a four-hour flight, or to try not using it at night when it may matter less.

Used in this fashion, the side effects are more tolerable and it empowers the patient to determine her best mode of dosing. Besides, she said, "If they take it exactly according to the labeling, they will be off it in three months anyway." Brubaker has found a way to tailor her treatments to her patient's desires.