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More than 200,000 men are diagnosed with prostate cancer each year in the United States. "Many of these cases do not need to be treated; however, even if a small fraction of patients need to be treated, this still amounts to tens of thousands of patients a year undergoing treatment for prostate cancer," said Daniel A. Hamstra, MD, PhD, associate professor and associate chair for medical education, and director of genitourinary radiation oncology at the University of Michigan in Ann Arbor, MI.
While research shows that surgery and radiation therapy have excellent cure rates for prostate cancer, there is still room for improvement.
"All of these therapies are associated with a significant risk for short- and long-term side effects that can greatly impact the patient's quality of life," said Jason A. Efstathiou, MD, DPhil, assistant professor at Massachusetts General Hospital/Harvard Medical School, in Boston.
Several new technologies and techniques hold great promise for treating prostate cancer, including stereotactic body radiation therapy, hypofractionation and proton beam therapy.
Stereotactic Body Radiation Therapy
Increasing the daily dose of radiation and decreasing the number of treatments can constitute an effective treatment for several types of cancers. This type of treatment is called stereotactic body radiation therapy (SBRT). During the last 7 years, clinical studies of SBRT in patients with prostate cancer have tested daily doses ranging between 7.0 and 10.0 Gray (Gy) (as compared to the 1.8-2.0 Gy normally used), Hamstra said.
"These higher daily doses administered with newer, state-of-the-art technologies enable the sparing of surrounding normal tissues better than older technologies," Hamstra said. In addition, "there is reason to think that by delivering the radiation 'faster' (i.e., more radiation therapy delivered in fewer days) one might achieve a more effective treatment outcome with fewer side effects. By using higher daily fractions, the total dose of radiation is substantially lower than what is typically used with small daily doses."
"As a newer treatment modality for prostate cancer, SBRT does not have long-term evidence to support it as the standard of care. However, initial results from a number of clinical trials suggest low rates of toxicity during the first several years that are at least as low as those observed when using conventional treatments and perhaps lower," Hamstra said.
"In addition, the early results looking at treatment efficacy suggest that SBRT may also result in curing prostate cancer (when measured by prostate specific antigen testing) that rival or are superior to those seen treated with conventional radiation therapy. Further clinical studies are needed."
Hypofractionation
Hypofractionation is a new approach to radiotherapy for prostate cancer. Standard radiotherapy is given 5 days per week for approximately 8 weeks.
"This is a longtime commitment for patients, and the treatment is resource intensive," said Howard Sandler, MD, chairman and Ronald Bloom Family Chair in the Department of Radiation Oncology at Cedars-Sinai Medical Center in Los Angeles. "Because of prostate cancer's biologic properties, especially its slow-growing nature, it may be more effective and have fewer side effects if the treatment is given over a much shorter number of treatments, perhaps as few as five instead of approximately 40.
"This new approach to prostate cancer treatment requires new technology as well," Sandler said. "If a treatment is given over only five treatments, the precision of each treatment must be increased versus standard therapy, and the radiation exposure of normal tissues must be strictly limited to avoid increased adverse effects."
The optimal radiation therapy schedule for this shortened approach remains under development and is under prospective testing.
Sandler has two concerns about hypofractionation. "Perhaps the biological modeling that led to the development of hypofractionation for prostate cancer is incompletely developed," he said. "This could result in a lower effective dose of radiation being delivered, which would be detectable with higher recurrence rates. The precision of current techniques may lead to treatments that inadvertently miss the target leading to under-dosage and incomplete tumor eradication."
Secondly, the hypofractionation approach could lead to higher toxicities. Of particular concern is the possible onset of bladder or urinary toxicity 3 to 5 years after treatment. "Thus far, these concerns are hypothetical and have not been observed among early studies," Sandler said. Nonetheless, the American Society for Radiation Oncology's Emerging Technology Committee issued a report in 2008 suggesting that hypofractionation be performed in the context of clinical trials to secure the necessary evidence to better assess its value.
Proton Beam Therapy
Unlike conventional x-rays, which pass in and out of a patient creating an "exit dose," protons enter a patient but stop at a prescribed depth where they deliver the bulk of their cancer-destroying energy. Called proton beam therapy, "this type of treatment allows radiation to be delivered precisely with a potentially improved and more homogeneous dose distribution to the target and lower dose delivery to surrounding normal tissues and to the body as a whole," Efstathiou said. Delivery of this noninvasive therapy requires a patient to lie flat on a table for a few minutes while the beam is delivered. Treatments are typically delivered once a day, 5 days a week, for approximately 8 weeks. Proton therapy has the potential to decrease the side effects associated with radiation therapy and improve the patient's quality of life.
On the down side, proton therapy may cost 50% to 70% more than traditional radiation therapies. This is primarily due to the high cost of building a proton beam facility. Clear data demonstrating improved treatment outcomes from proton beam therapy will take time.
Karen Appold is a medical writer based in Royersford, PA.
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