- Associated Press - Wednesday, February 2, 2011

NEW YORK (AP) - A new experimental test may someday help doctors with one of the most vexing problems in cancer therapy: identifying which prostate cancer patients need aggressive treatment.

Currently, once prostate cancer is diagnosed, doctors have no reliable way to know which cases are life-threatening. Most are not. So doctors have a difficult time determining whether they should monitor the cancers to see if they progress or recommend immediate treatment, such as surgery or radiation. Both treatments can cause problems, such as incontinence and impotence.

The dilemma results in overtreatment, such that about 48 men are treated for every life saved, says Dr. Ronald DePinho of the Dana-Farber Cancer Center in Boston.

But DePinho and colleagues have created a test they say might help doctors identify dangerous tumors more accurately than is possible now. In results published online Wednesday by the journal Nature, the scientists showed an improvement in accuracy to 91 percent from 84 percent.

When applied to prostate cancer samples, the gene test indicates “how this particular cancer is wired to behave,” DePinho said.

Drawing on research in mice, DePinho and colleagues identified four genes whose combined activity within cancers appears to drive prostate tumors toward being lethal. The genes are involved in processes like growth and ability to invade other tissues.

Then the researchers tested whether the combined activity of those genes also predicted cancer outcome in men, with a series of tests in human tumor samples.

In the largest test, they looked at 405 tumor specimens from men who’d been diagnosed between 1983 and 2004. Thirty-eight cases turned out to be lethal. Researchers looked for the chemical signatures of gene activity in the samples and tested how accurately that could classify tumors as lethal or not.

By itself, the gene test performed about as well as a combination of current indicators: age at diagnosis, indications of tumor spread and a “Gleason score” that assesses the appearance of tumor cells under a microscope. That standard approach was accurate 84 percent of the time in the study.

But accuracy rose to 91 percent when researchers combined that approach with the gene test. The combination “robustly predicted which men were going to die of the disease,” DePinho said.

The rights to develop the test have been licensed to a company that DePinho co-founded and in which he holds a financial interest.

Experts not connected with the study praised the work but said more research on the gene test is needed.

“It’s early still, but it’s pretty exciting,” said Dr. Eric Klein of the Cleveland Clinic. “This is a step in the right direction, without question.”

Dr. Angelo De Marzo, a professor of pathology, oncology and urology at the Johns Hopkins School of Medicine in Baltimore, called it “extremely interesting, promising, amazing work.”

It will take more research to see whether the gene test really could help doctors make treatment recommendations with more confidence than they can now, and in what situations, he said. The test might prove useful when prostate cancer is diagnosed from biopsy samples, or in deciding on further treatment after a man’s prostate has been removed, he said.

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