Looking for a sign of deadly prostate cancer

It may soon be possible to distinguish aggressive prostate tumors requiring immediate treatment from those that grow slowly and can be safely ignored, a problem that has vexed oncologists and patients for decades.

Looking at the complete profiles of chemicals produced by prostate tumors, researchers found that levels of sarcosine -- a simple derivative of the amino acid glycine -- are substantially higher in patients with aggressive tumors, they reported Wednesday in the journal Nature.Levels of sarcosine in the blood could be easily and cheaply identified with a simple test that could replace or complement the prostate-specific antigen, or PSA, test now widely used in prostate cancer patients. The PSA is very useful for identifying the presence of tumors, but says little about their ultimate prognosis.

Perhaps equally important as the metabolic findings, tests in laboratory dishes showed that adding sarcosine to benign tumors dramatically increased their aggressiveness, while blocking sarcosine production in aggressive tumors rendered them much less potent.

The findings may eventually lead to new ways of preventing the spread of the tumors, said Dr. Arul M. Chinnaiyan, a pathologist at the University of Michigan Medical School and senior author of the Nature paper.

Prostate cancer is the most common form of cancer in American men, with an estimated 186,320 cases diagnosed last year, according to the American Cancer Society. About 28,660 men died of the disease in 2008. And 80% of men over the age of 80 develop it.

The conundrum for clinicians is that while many of the tumors can be highly aggressive and immediately life-threatening, others are so slow-growing that they can be safely ignored, a concept known as watchful waiting. But there has not been any good way to distinguish between the two forms.

If physicians could distinguish between the forms, they could minimize unnecessary treatment of patients who are likely to die of other causes before their prostate tumors progress, Chinnaiyan said. That treatment is expensive and can lead to side effects such as impotence and incontinence.

To address the problem, the Michigan group used the new science of metabolomics, in which researchers look at all the metabolites -- chemicals produced during metabolism -- associated with an organ. They studied 1,126 metabolites in 262 samples of healthy prostate tissue, localized prostate tumors and aggressive or metastatic prostate cancer.

The researchers identified 10 chemicals whose levels increased during prostate cancer progression. The most dramatic results were with sarcosine: Levels were elevated sharply in 79% of metastatic cancer patients and less sharply in 42% of early stage patients. The chemical was not found at all in cancer-free samples.

The chemical was also readily detected in the urine of prostate cancer patients, suggesting that it may be possible to develop a simple, noninvasive test for the tumor. Their overall findings have to be validated in larger studies, Chinnaiyan said, but a urine test could be available in three to five years.

To the researchers' surprise, they also found that manipulating sarcosine levels in the test tube could alter the course of tumor growth, suggesting that the chemical plays an as-yet-unknown role in metastasis. If that proves to be the case, chemicals that block its production could serve as new cancer drugs.

The team is now taking a closer look at the other chemicals whose concentrations change with tumor progression. Using a panel of chemicals rather than just one would provide a more accurate diagnosis, Chinnaiyan said.

Analyzing metabolites is "particularly attractive" because it could provide an accurate assessment of tumors' cellular physiology and biochemical activity, wrote Dr. Cory Abate-Shen and Dr. Michael M. Shen in an editorial accompanying the paper. The Michigan team's is the first application of metabolomics to tumors, and the researchers speculate that further studies could produce diagnostic markers for a broad variety of cancers.