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Originally published August 16, 2011 at 9:00 PM | Page modified August 17, 2011 at 9:50 AM

Research aims to prevent overtreatment of prostate cancer

Researchers at the Fred Hutchinson Cancer Research Center have identified genetic markers associated with aggressive prostate cancer. They say their work could lead to the development of a simple blood test that could help determine who should receive aggressive treatment and who could opt for more conservative approaches.

Seattle Times staff reporter

quotes no more Bozos title is an oxymoron here. There is a central dumbness to this... Read more
quotes Well, I think that's the attitude that leads to so much overtreatment in the US... Read more
quotes Go to the medical library. Do the research and don't accept scare tactics. Read more

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Janet Stanford has been studying prostate cancer for years; she knows the statistics and can recite them from memory:

Prostate cancer is the second most common cause of death from cancer in men in the United States.

More than 240,000 cases will be diagnosed this year. And close to 5,500 of them will be in Washington state.

The researcher and her colleagues at the Fred Hutchinson Cancer Research Center have zeroed in on the overtreatment of the disease — which in men with slow-growing and seldom lethal prostate cancer can result in impotence and the loss of bladder control, among other side effects.

Their findings, published online Tuesday in the medical journal Cancer Epidemiology, Biomarkers and Prevention, could lead to a simple blood test to determine who should receive aggressive treatment and who should consider more conservative options.

Their discovery won't help with early detection of the disease but could help with the likely outcome of the illness, the scientists say.

Stanford and her colleagues at the Hutch analyzed the DNA in blood samples from more than 1,300 prostate-cancer patients in and around Seattle and identified 22 genetic variants associated with aggressive, lethal prostate cancer.

They looked through 937 genetic variants among 156 genes that they hypothesized were associated with tumor growth and its likelihood of spreading and proving fatal.

An analysis by Stanford and her colleagues of close to 3,000 patients in Sweden whittled those down to five variants among five genes.

"The question was simple: How can we identify the prostate cancers that are destined to kill? It's often difficult to distinguish between harmless and aggressive cancers," said Stanford, who says she became involved with prostate-cancer research because there was a dearth of information during the nascent stages of her career, and also for personal reasons. Her father is a prostate-cancer survivor.

Part of the challenge, she says, is that similar tumors can produce far different outcomes among patients, with one man dying of his cancer a few years after diagnosis and another man living for decades.

"How can we avoid putting men through treatment that may not be necessary, and often rough?"

Previous studies have found that about three-quarters of men with indolent, or slow-growing, tumors, receive aggressive therapy, ranging from radiation therapy to hormone therapy to the complete removal of the prostate.

Overtreatment, Stanford says, is no one's fault. The tools available are lacking, leading doctors to err on the side of caution, potentially overtreating a condition because their priority is to keep the patient from dying.

"We're motivated by good things, but we don't always get the best outcomes," said Robert Resta, a genetic counselor at Seattle's Swedish Medical Center who is not affiliated with the study. "This work is a great first step."

While a number of studies have looked at family and genetic history to determine cancer risk, Stanford's work is the first time that genetic history has been used to determine the aggressiveness of a tumor.

Stanford's blood test isn't meant to replace anything. Rather, it would complement existing tools, becoming part of a process that starts as soon as a routine prostate exam gives a doctor pause.

From there, a prostate-specific antigen (PSA) test measures proteins produced by cells of the prostate gland. If the results warrant it, a biopsy is performed and the tissue rated on a scale of 1 to 10, with 8 and up indicating an aggressive and often lethal form of cancer that may require radiation therapy or surgery, while scores of 2 to 4 suggest a possibly indolent tumor meriting more conservative treatment.

"We need to be able to stratify patients, and this has the potential to help do that," said Stanford.

This is when Stanford's blood test comes in.

If 4 to 5 biomarkers are found in the blood, chances are that the patient has a form of prostate cancer that requires aggressive treatment, whereas 1 or 2 biomarkers suggest that the cancer is potentially slow growing and could benefit from active surveillance — routine PSA tests, prostate exams and biopsies.

"We need every tool we can get to help with prognosis," Stanford added.

If her work proves successful — which means the findings would hold across ethnic lines, ages and stages of cancer progression — it could also help ease the economic burden created by the overtreatment of nonaggressive tumors. About $2 billion to $3 billion is spent annually in the U.S. on initial therapy alone, according to Stanford.

Roberto Daza: 206-464-3195 or rdaza@seattletimes.com

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