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Biomarkers May Predict Aggressiveness of Prostate Cancer
Date:5/5/2009

Cancer expert is wary of finding, however

TUESDAY, May 5 (HealthDay News) --Three molecules associated with prostate cancer might provide the long-sought markers that could discern which tumors are life-threatening and need aggressive treatment, a new study indicates.

The currently hot debate about the value of screening for early detection of prostate cancer hinges on the fact that the cancer is usually so slow-growing that there is no lifesaving benefit from treatment such as surgery, which can cause impotence and incontinence. Recent studies in the United States and Europe found at best limited benefit from routine prostate cancer screening, and new guidelines from the American Urological Association say that many men do not need annual screening tests.

As yet, there are no established markers to distinguish which prostate cancers grow fast enough to require such treatment. The new study, published in the May 5 issue of the Annals of Internal Medicine, identifies three such markers.

"We're not trying to say these are the only markers," said study author Dr. John Concato, a professor of medicine at Yale University and director of the clinical epidemiological research for the Veterans Affairs Connecticut Healthcare System. "This is a proof of principle."

Measuring levels of the markers might someday help guide treatment of men with prostate cancer, he said. "If the markers are positive, that might be an indication that more aggressive therapy is indicated," Concato said.

However, that claim was challenged in an accompanying editorial by a cancer specialist.

The findings stemmed from an examination of tissue samples from 1,172 men diagnosed with prostate cancer at VA centers in New England. Researchers looked at a number of possible biomarkers and identified three associated with a higher risk of death from the cancer: bcl-2, a molecule that helps regulate cell death; p53, a protein produced by a tumor-suppressor gene; and microvessel density, the excessive production of blood vessels needed for growth of a cancer.

Levels of all three markers were significantly higher in the men who died of prostate cancer in the subsequent 11 to 16 years, the study found.

Concato said the study is just a first step toward use of the biomarkers to guide prostate cancer treatment. "Other groups should replicate our results," he said. "Based on these results, there should be an effort at developing therapies that attack the mechanisms reflected by these markers."

Concato said he has proposed a clinical trial that "would treat patients based on marker status, as positive or negative."

The editorial by Dr. Edward P. Gelmann, chief of the division of hematology/oncology and deputy director of the Herbert Irving Comprehensive Cancer Center at Columbia University, challenged the value of all three biomarkers.

A number of previous studies have shown that results of p53 tests "are not reproducible from one laboratory to the next," Gelmann said. "There is great variability in both technique and results." Though p53 has been studied as a biomarker for a number of cancers, he said, it is used only for one rare malignancy, transitional cell carcinoma of the blood.

As for bcl-2, Gelmann said that the number of cases in the study with a positive reading was too small to provide proof of its predictive power. "To prove it has prognostic significance would require would require a larger trial," he said.

And the measure of blood vessel density done in the study was not necessarily reproducible, Gelmann said. "It was done by an individual observer without anyone else checking it," he said.

In response, Concato said that "the editorial doesn't mention several major strengths of the study, and it misrepresents what was known before we did our study."

"For example, showing a link between markers taken at diagnosis and long-term mortality had not been shown before," he said. "Perhaps the editorial is concerned about inappropriate, excessive use of these markers -- and, if so, we would agree."

More information

The U.S. National Cancer Institute has more on prostate cancer.



SOURCES: John Concato, M.D., professor, medicine, Yale University, and director, Clinical Epidemiological Research Center, Veterans Affairs Connecticut Healthcare System, New Haven, Conn.; Edward P. Gelmann, M.D., chief, division of hematology/oncology, and deputy director, Herbert Irving Comprehensive Cancer Center, Columbia University, New York City; May 5, 2009, Annals of Internal Medicine


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