Higher doses of radiation in fewer treatments proved safe, effective for low-risk prostate cancer, study finds

ScienceDaily (June 2, 2011) — In a multicenter clinical trial, UT Southwestern Medical Center researchers have found that higher doses of stereotactic radiation therapy requiring fewer treatments are safe and effective for patients with low-to-intermediate-risk prostate cancer.

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Results of the trial, available in the Journal of Clinical Oncology, showed that stereotactic body radiation therapy (SBRT), which delivers ultra-precise radiation, was effective in treating patients with localized prostate cancer in five 30-minute sessions every other day over two weeks. That compares to the typical radiation protocol for prostate cancer of 42 to 45 daily treatments administered over eight to nine weeks.

"We were trying to develop a fast, convenient, outpatient, non-invasive treatment," said Dr. Robert Timmerman, vice chairman of radiation oncology and professor of neurological surgery and senior author of the study. "In the low-risk population, there are a lot of good options, but none of them are altogether convenient. The most convenient treatment would finish quickly without the need for a prolonged recovery."

SBRT has been used in the last decade to treat patients with lung, liver and brain cancers. The current study tested whether high-potency treatments would work in a moving target like the prostate, which moves considerably due to normal bladder and bowel filling.

"We're trying to kill the prostate cancer, but without injuring the urethra, the bladder or the rectum," Dr. Timmerman said. "Each treatment had to be very potent in order to get the full radiation effect in only five treatments."

To avoid injury to healthy tissue, researchers used beams of radiation that were just millimeters larger than the target itself. That narrow scope helped avoid consequences such as rectal injury, impotence and difficulty urinating.

Prostate cancer is the most common cancer in men, with some 200,000 diagnosed each year in the U.S. About half of those who are treated undergo radiation therapy, typically for eight weeks. Not everyone is cured, however, because some tumors are resistant to radiation.

In the current clinical trial, researchers tested escalating doses for safety levels in 45 patients enrolled from November 2006 to May 2009. In a 90-day follow-up procedure, they looked at how much injury occurred in adjacent areas, including the rectum or urethra, and any changes to the patients' quality of life.

"There were a few more complications associated with higher doses, but they were fairly predictable and rarely severe," said Dr. Yair Lotan, associate professor of urology and a co-author of the study. "By giving these higher doses, we might be able to kill more resistant tumors with shorter treatments."

In the next stage of the clinical trial, a larger group of patients will be treated at one dosage level, and follow-up will be 18 months.

Other UT Southwestern researchers involved in this study were Dr. Paul DeRose, radiation oncology resident; Dr. Xian-Jin Xie, associate professor in the Harold C. Simmons Comprehensive Cancer Center; Jingsheng Yan, statistician; Dr. Ryan Foster, assistant professor of radiation oncology; Dr. David Pistenmaa, professor of radiation oncology; and Susan Cooley, senior research nurse in radiation oncology.

The study was supported by the Department of Defense.

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Obesity linked to higher risk of prostate cancer progression

ScienceDaily (May 16, 2011) — Even when treated with hormone therapy to suppress tumor growth, obese men face an elevated risk of their prostate cancer worsening, researchers at Duke University Medical Center have found.

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The research, reported at the American Urological Association annual meeting on May 15, 2011, advances the link between obesity and prostate cancer, which has generated research interest in recent years as the incidence of both conditions remains high and often overlaps.

"Over the past decades, there has been increasing prevalence of obesity in the U.S. and Europe, and a high rate of prostate cancer that is the second-most lethal cancer for men," said Christopher J. Keto, M.D., a urologic fellow at Duke University Medical Center and lead author of the study.

An estimated one in six U.S. men will be diagnosed with prostate cancer during his lifetime, according to the American Cancer Society; additionally, one in three U.S. men are obese.

To examine the role obesity may play in prostate cancer, Keto and colleagues at Duke identified 287 men whose diseased prostates had been removed at five U.S. Department of Veteran Affairs hospitals from 1988-2009.

Because their cancers had reappeared, the men had also been given androgen deprivation therapy (ADT). The chemical inhibits production of the male hormone testosterone, which fuels prostate tumors.

Men in the study group who were overweight or obese had a three-fold increased risk of cancer progression compared to normal-weight men, despite receiving the same treatment.

Additionally, overweight men had more than a three-fold increased risk of their cancer spreading to the bone compared to normal-weight men, while obese men had a five-fold increase in the risk of metastases.

Keto said additional studies are needed to determine why heavy men fare worse than normal-weight men, even when treated similarly. One area of scrutiny may be the dosage of ADT.

"We think perhaps obese men may require additional ADT," Keto said. "The dose is the same regardless of weight, while most drugs are dosed according to weight."

Stephen J. Freedland, M.D., associate professor of urology in the Duke Prostate Cancer Center and senior author of the study, said the findings build upon the Duke group's broader research efforts into the connection between obesity and prostate cancer.

"By being thematic in our research we can really get to the bottom of something," Freedland said. "The study supports a growing body of literature showing that obese men with prostate cancer do worse. Our next step is to figure out why."

Freedland said knowing that heavy men are at higher risk for bad outcomes could lead to better interventions. He said the Duke group has launched a new trial to test the effects of diet and exercise on overweight and obese men whose prostate cancer treatment includes hormone therapy.

"If obesity is bad for prostate cancer, we may have to be more aggressive in our treatment," he said. "Ultimately, we aim to learn why, which in turn can lead us to better treatments for these men."

In addition to Keto and Freedland, study authors included William J. Aronson, M.D.; Martha K. Terris, M.D.; Joseph C. Presti, M.D.; Christopher J. Kane, M.D.; and Christopher L. Amling, M.D.

The study was funded by the Department of Defense, U.S. Department of Veterans Affairs, the National Institutes of Health, and the AUA Foundation/Astellas Rising Star Award.

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