Urine test may improve prostate screening

Analysis might shed light on iffy PSA scores

Every year hundreds of thousands of men getting a physical examination find themselves in a gray zone, showing signs of prostate cancer on a common blood test. A new urine analysis might clarify which of these men is most at risk and should take the more definitive, and invasive, step of getting a prostate biopsy.

Beyond a physical exam of the prostate, the standard screening method for prostate cancer is a blood test that measures levels of a protein called prostate specific antigen, or PSA. Although it’s a rough measure at best, an elevated PSA score is enough to send 600,000 to 1 million U.S. men each year to get a biopsy.

Writing in the Aug. 3 Science Translational Medicine, scientists who devised a test based on levels of two compounds detectable in urine found that the combination may serve as a marker of cancer and take some of the guesswork out of interpreting PSA scores, which are often unreliable in predicting malignancies.

“I think this is ready for the clinic,” says study coauthor Scott Tomlins, a pathologist at the University of Michigan Medical School in Ann Arbor. “In the near future, it should be available to patients.”

The two biomarkers have been previously linked to prostate cancer. Prostate cancer antigen-3, or PCA-3, shows up in excess in 95 percent of prostate tumors. The other biomarker is the fusion of two genes called TMPRSS2 and ERG. This fusion gene turns up in roughly half of prostate cancers, previous research has shown. When locked together, the TMPRSS2 part of the resulting gene serves as an “on” switch for the ERG gene. The cell then overproduces the protein encoded by ERG, Tomlins says.

The researchers tested 1,065 men who, based on their PSA level, had been scheduled for a prostate biopsy. Before that tissue extraction procedure, each man submitted a urine sample, from which the study researchers calculated a score using levels of TMPRSS2-ERG and PCA-3. The men were then divided into three equal-sized groups by highest scores (having a high level of either TMPRSS2-ERG or PCA-3), lowest scores (those with low amounts of both biomarkers), and those that fell between.

The biopsies subsequently revealed that 69 percent of men with the highest scores had prostate cancer. Rates were 43 percent in the middle group and only 21 percent among men with the lowest scores.

For men with a slightly elevated PSA score, the new urine test could provide a better idea of who needs a biopsy, says Tomlins. Biopsies risk more than discomfort; some can cause infection. Men who score low on the new combination test might put off a biopsy but repeat the urine test a year later, Tomlins suggests.