Blood Test May Spot Aggressive Prostate Cancer

A reliable screen would help doctors match treatments to individual patients

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By E.J. Mundell
HealthDay Reporter

MONDAY, Oct. 17, 2005 (HealthDay News) -- Ideally, the type of prostate cancer a man has -- aggressive or slow-growing -- should guide decisions as to whether he needs intensive treatment or simply "watchful waiting."

Trouble is, there's currently no quick, reliable means of gauging just how deadly a particular prostate malignancy might be. That's why researchers are excited about new findings for a blood protein "biomarker" called MDM2.

In a preliminary study, relatively high blood levels of MDM2 were associated with three distinct signs of aggressive prostate cancer. If the findings are replicated in a larger trial, an MDM2-based test might someday become a routine part of patient care, experts say.

"To be able to say which tumors are likely to progress and become problematic vs. those that are much more indolent or slow-growing would be very helpful in allowing a patient to make a very important decision: whether he wants active treatment or not," explained Dr. Durado Brooks, director of prostate and colorectal cancer at the American Cancer Society.

Brooks believes MDM2 "has a lot of potential" as a viable prognostic indicator, but he added that more study is needed.

The findings were reported Monday at the American Society for Therapeutic Radiology and Oncology annual meeting in Denver.

Prostate cancer is the second most common cancer diagnosed in men (skin cancer is first) and the second leading cancer killer for men after lung cancer. According to the American Cancer Society, over 232,000 men will be diagnosed with prostate cancer this year, and more than 30,000 will die of the disease.

In their study, researchers at the Fox Chase Cancer Center in Philadelphia tracked the outcomes of 469 prostate-cancer patients for an average of nearly six years. At the same time, they routinely tested for levels of MDM2 and other biomarkers in the men's blood. All of the men received standard treatments such as radiation and short- or long-term hormone-deprivation therapy.

The researchers looked at the relationship between blood biomarkers and three signs of aggressive prostate cancer: biochemical failure (rising PSA levels), the spread of malignancy to sites outside the prostate, and death.

While other markers were correlated with one or two of these outcomes, only high blood levels of MDM2 were linked to all three, the researchers reported. Men with high concentrations of MDM2 were much more likely to display aggressive, metastatic disease than men with low levels.

Besides helping to spot those patients needing aggressive therapy, a good prognostic blood test could also spare men with less-threatening, slower-growing tumors troublesome treatments.

"For example, if the cancer is very slow-growing and a man has other medical problems or has an anticipated lifespan of less than seven or eight years, it's sometimes not worthwhile to operate or provide radiation for that prostate cancer," Brooks said.

Lead researcher Dr. Alan Pollack noted that any test that could reliably determine prostate cancer type would also aid research. "We can learn about which types of cancers are anticipated to respond to [specific] treatments, for what reason," he said.

Pollack, who is chief of radiation oncology at Fox Chase, said MDM2 is also being investigated as a potential therapeutic target.

"MDM2 interferes with p53, a very important molecule in regulating cancer cell death in response to radiation and perhaps hormone therapy," he explained. "We want cancer cells to die and MDM2 interferes with that -- if MDM2 is high, then the cells seem to be protected from radiation and hormone therapy."

Already, he said, drug companies are developing compounds that may thwart the proteins' attempt to shield cancer cells from destruction. "The results are very promising that by knocking out MDM2 you might be able to improve responses to radiation and hormone therapy," Pollack said.

In the meantime, work on MDM2 as a prognostic indicator continues, with a larger trial the obvious next step, according to Brooks. "It has to be looked at in a larger pool of men with various stages of prostate cancer," he said.

More information

For more on prostate cancer, head to the American Cancer Society.

SOURCES: Durado Brooks, M.D., M.P.H., director, prostate and colorectal cancers, American Cancer Society; Alan Pollack, M.D., Ph.D, chairman, radiation oncology, Fox Chase Cancer Center, Philadelphia; Oct. 17, 2005, presentation, American Society for Therapeutic Radiology and Oncology annual meeting, Denver

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