Seed Snipers Gunning for Cancer Tissue

Whether the growing number of prostate cancer patients being treated today can be attributed to increasing incidents of prostate cancer or to better technology enabling physicians to spot it sooner can be difficult to pinpoint.
Whatever the case, one of the newest treatments for prostate cancer - brachytherapy - is revolutionizing medical practice for its ability to accurately target and kill the glandular tumors by exposing them to tiny radioactive seeds. And as long as Medicare and private insurers continue reimbursing such procedures in a favorable way, prostate brachytherapy promises to be one of the most widely practiced outpatient cancer treatments in the coming years.
"Regulatory and technological developments have made prostate brachytherapy huge in the outpatient area," said Mike Krachon, market manager for Covington, GA-based C.R. Bard's Urological Division. "I’m not sure there are greater incidences of prostate cancer today, but the good news is we're finding and treating more prostate cancers than ever before, and it's saving so many lives."
Brachytherapy actually is one of the latest weapons in the oncologist's arsenal for treating prostate cancer, and has only been widely practiced in the U.S. since the early 1990s. Other treatments include radical prostatectomy (the surgical removal of the gland and still the gold standard), external beam radiation, hormone therapy (which promotes shrinking of the prostate and tumor) and cryotherapy (which entails freezing the tumor in efforts to kill the cancer).
Prostate brachytherapy involves placing a specific dosage of tiny radioactive seeds into the prostate gland through hollow needles. Physicians use a variety of approaches, such as ultrasound, to ensure proper placement of the seeds.
There are essentially two kinds of prostate brachytherapy. One technique, low-dose rate (LDR) brachytherapy, involves permanently implanting the seeds in the patient's prostate using catheters or special applicators. The patient goes home following the procedure. The other, high-dose rate (HDR) brachytherapy, involves exposing the tumor to higher dose seeds for short periods of time. HDR delivers a dose greater than 100 centigrays (cGy) per minute for 5 to 30 minutes, compared with LDR, which delivers a dose of 40 to 60 cGy per hour over several days, according to Plymouth Meeting, PA-based ECRI, a technology evaluation firm.
HDR is typically used in patients with advanced stages of prostate cancer and allows the oncologist to adjust and conform the radiation dose during the treatment. HDR also is often used as a boost in combination with other treatments including chemotherapy and external beam radiation. In HDR, needles guided by a template sewn to the patient's perineum are inserted for seed delivery. Patients typically receive twice-daily HDR treatments while remaining an inpatient for several days.
A Litany of Benefits
Prostate brachytherapy has a litany of benefits, including less damage to the healthy tissue surrounding the tumor, fast recovery times and better accuracy (especially with image-guided techniques). "Prostate brachytherapy also spares nerve damage, minimizes impotence and incontinence and has much fewer side effects depending on whose results you look at," said Tim Clarke, product manager for Palo Alto, CA-based Varian BrachyTherapy.
Prostate brachytherapy techniques have become so refined, in fact, that some clinical researchers claim the procedure may actually extend lives longer than prostatectomy.
"When compared to surgery, there is simply no comparison with equal or better long-term results and significant advantages in terms of recovery time and long-term complication rates, particularly impotence," said Dave Stiles, vice president, Sales and Marketing, for North American Scientific Inc., Chatsworth, CA. Moreover, he added, complication rates, primarily impotence and incontinence, are significantly lower than with other therapies, with long-term results approximating incontinence and impotence rates in the general male age group population.
"LDR is true conformal radiation because it applies a dose only to the target areas in and adjacent to the prostate," Stiles added. "This poses no threat to anyone the patient interacts with, but by providing continuous dose to the target area, the cancer cells never get a chance to 'rest' as they do with other types of radiation therapy, meaning the cancer cells never get a chance to repair themselves and divide. This is the reason for [the procedure's] excellent long-term clinical results."
In a market that began with two competitors in 1998 to nearly 20 today, prostate brachytherapy is now used to treat more than a quarter of all newly diagnosed prostate cases (roughly 40,000 patients a year) and has seriously eroded prostate surgery caseloads, according to market researcher MedTech Insight. "Technology has made prostate brachytherapy a very stable and accepted practice," Clarke said. "Today, survival rates for LDR are comparable to those for prostatectomy."
Radiation-filled seeds have a clinical track record, too. "Interstitial seeding has established itself over the past 10 years based on a large body of clinical experience as an excellent treatment option for early stage prostate cancer," said Stiles, adding that while five- and 10-year recurrence rates vary slightly by study, patients overall have over a 90 percent probability that their cancer will not reoccur with seeds.
For outpatient urology practices, where prostate diseases account for more than half of all visits, LDR brachytherapy may one day be a boon. "LDR is positioned perfectly for the ambulatory setting because no major retrofits are needed, unlike the heavy shielding that's required with HDR," said William Walker, M.D., president and CEO, Comprehensive Physics and Regulatory Services (CPRS), Point of Rocks, MD. Walker said LDR prostate brachytherapy procedures outnumber HDR procedures 10 to 1 in the outpatient arena.
Favorable Reimbursement
Insurers also have taken notice, and it's not surprising that prostate brachytherapy is getting their attention these days. A typical treatment costs an average of $35,143, compared with external-beam radiation therapy ($59,455) and androgen deprivation therapy ($69,244), according to a January 2007 report by Reuters Health.
Payments for prostatectomies remain fairly lucrative, and reduced reimbursement for external beam and intensity modulated radiation therapy (IMRT) may somewhat temper strong growth in prostate brachytherapy procedures, according to a 2005 report by market researcher Frost & Sullivan. Medicare set a fixed cost for prostate brachytherapy procedures in 2002, but some of the agency's recent rule changes have helped. For example, the agency's reimbursement payment structure for implantable seeds eliminated restrictive monetary caps on brachytherapy seed reimbursement, enabling physicians to decide the seed type, number of seeds and advanced seed technologies, Frost & Sullivan noted.
When Medicare approved prostate brachytherapy in the outpatient setting several years ago, it opened huge opportunities for urologists, who conventionally just collected fees when such procedures were performed in the hospital, said Walker. "This was a huge change for physicians," he said. "Many have their own outpatient treatment centers that were underutilized before prostate brachytherapy was approved." Walker added that urologists today have much greater control, and thus earn more revenues, for prostate brachytherapy procedures.
State of Innovation
The basic gear needed to perform prostate brachytherapy includes: seed implants (made from radioisotopes palladium or iodine); templates, needles, catheters; treatment applicators; accessories such as steppers (which move the seeds from a shielded device through the guide tubes and into the treatment applicators), stabilizers and fixation devices; imaging equipment; afterloaders; and treatment planning software, which is used to ensure the accurate amount of radiation delivery to the tumor.
CT or MR imaging scans can be used to define the tumor volume and location to optimize radiation dose distribution. Treatment planning software functions can include source-positioning and dwell-time parameters, catheter tracking, three-dimensional reconstruction, dose reduction algorithms and dose-distribution analysis. Some treatment planning computers also offer optional external beam radiotherapy planning, according to ECRI.
Numerous niche companies specialize in seeds and strands. Others provide brachytherapy accessories and supplies, while some market special treatment planning software. Vendors may offer complete brachytherapy suites, integrating all aspects of the brachytherapy treatment, from patient preparation and applicator insertion to imaging, treatment planning, delivery and verification.
Some firms, such as CPRS, have addressed the needs of smaller outpatient providers that can't afford on-site clinical expertise like medical physicists. For example, CPRS has an in-house physicist who oversees scans and treatment plans that clients send over the Internet. "We allow our clients to transmit their studies and we load them into a treatment plan with physics oversight," Walker said. "Most urologists don't have the staff for a physicist." Walker said CPRS has helped numerous surgery centers set up their own prostate brachytherapy programs, in addition to providing such services as licensing and training.
While imaging modalities are in a constant state of innovation, ultrasound improvements have given urologists more powerful ways to plan and deliver treatment. "The development of transrectal ultrasound was the imaging advance that made prostate seeding a practical clinical option," said Stiles. "The quality of ultrasound images has improved over the years and there are now several systems on the market designed primarily for prostate brachytherapy."
Recent innovations have focused on improving methods for delivering, controlling and monitoring the level of radiation the patient receives. "The biggest challenge for prostate brachytherapy now and in the near future is ensuring that the seeds are accurately delivered and don't shift inside the gland," said Krachon. New developments in strand materials and delivery have given physicians greater control. Stranding adds precision to the seed placement and reduces OR time.
For example, Stiles said NAS' SurTRAK, introduced last year, embeds the seeds in a resorbable strand material. The seeds are precisely positioned within the molded strand at the position required by the treatment plan. "Stranding assures that the seeds stay in the exact position called for in the plan for the first several months when the vast majority of the clinical dose is delivered," said Stiles. "Seed placement is crucial, though with loose seeds placed in the prostate the position sometimes shifts as the gland swells at the time of implantation due to irritation caused by the placement needles."
Stiles indicated the SurTRAK strand is unique for its ability to place the first seed at the very edge of the needle bevel. "This puts the first seed very close to the optimum position called for by the treatment plan, as opposed to other products that place the first seed as much as 5 mm behind the ideal position due to the use of a plug at the tip of the needle to hold the strand in place," he added.
C.R. Bard's QuickLink Delivery System, meanwhile, provides a cartridge-based device designed to assemble brachytherapy seeds, spacers and its branded synthetic absorbable monofilament connectors called SourceLink into seed trains of variable lengths and with variable seed-to-seed spacing as predetermined by the physician. Krachon describes the QuickLink system as "LEGO-like blocks that allow the physician to build any strand instead of manipulating each element."
Real-Time Planning
New image-guided techniques and advances, such as real-time intraoperative planning (in which seed placement is decided at the time of the procedure), are giving physicians more flexibility and control. Prostate tumors and the seeds used to treat them are moving targets. These new techniques enable doctors to acquire better patient images needed for planning and delivering brachytherapy treatments for their patients.
Approximately 900 radiation oncology centers around the world use Varian's VariSeed treatment planning software for guiding the placement of permanent prostate seed implants in LDR prostate brachytherapy. Because it incorporates dynamic dosimetry, VariSeed gives physicians more assurance they are delivering the intended dose, according to the company. Varian's recently introduced Vitesse module, which it added to its BrachyVision treatment planning software "streamlines workflow and allows physician to create treatment plans quickly, on the fly," Clarke said. The module uses ultrasound (eliminating the need for CT scan) for treatment planning and allows the physician to plan HDR at the same time needles are being placed.
On the horizon?
Physicians today are constrained by conventional imaging techniques, while newer combination therapies involving PET and CT, and SPECT and CT are showing promise, experts observe. Researchers at Emory University in Atlanta have also recently identified promising new radiotracers for imaging evaluation.
"Imaging modality combinations will be a significant thing to watch in the coming years," said Clarke. "Image-guided applications are becoming very important, and new guidelines are coming out for this."
Krachon said the biggest innovations to come will continue to be advances that simply give physicians more control. "The biggest challenge for prostate brachytherapy has been finding better ways to accurately deliver the seeds and ensure they don't shift inside the gland," he said.