New urine test predicts high-grade cancer

Charlie Schmidt

Editor, Harvard Medical School Annual Report on Prostate Diseases

by Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Disease

Suspicious findings from prostate cancer screening are often followed by a procedure most men would prefer to avoid: a prostate biopsy. But what if biopsies actually could be avoided on the basis of non-invasive test results? Screening tests are moving in that direction, with some intriguing results. One of them, the Prostate Health Index blood test, combines measures of three forms of prostate-specific antigen (PSA) into a score that helps doctors predict if a cancer is likely to progress, with an aim to circumvent biopsies that aren’t necessary. Another non-invasive test, called the PCA3 assay, measures genetic evidence of aggressive cancer in urine samples, and generates a score designed to help doctors assess the need for a repeat biopsy. Though approved by the Food and Drug Administration, these tests aren’t perfect, and experts question the reliability of the PCA3 test in particular.

Now researchers are considering the value of a new test that also looks for evidence of high-grade prostate cancer in urine. The results were reported in the Journal of the American Medical Association last April. Called the “urine exosome gene expression assay,” it measures not just PCA3 but also two other genes associated with high-grade disease: ERG and SPDEF. The test combines those measures into a diagnostic score that “could help determine if an initial prostate biopsy is warranted,” said its co-developer Dr. Michael Donovan, a pathologist and researcher at The Mount Sinai Hospital in New York. According to Donovan, the goal is to limit the number of prostate cancer biopsies, which are costly, painful, and prone to hospital-acquired infections.

The study enrolled 1,563 men from 22 community and academic urology clinics in the United States. According to results with a final grouping of 519 men, assay scores over a “cut-off” value of 15.6 predicted high-grade cancer correctly 92% of the time. The assay didn’t always get it right: 12 men were misdiagnosed as having low-risk cancer when they in fact had higher-grade disease.. But most of those tumors, Donovan said, fell into an intermediate-risk category that some doctors would consider eligible for active surveillance instead of treatment.

The genes measured reside in small vesicles called exosomes that are secreted by prostate cells. For the test, men have to provide a “first-catch” urine sample. That’s because prostate exosomes are concentrated in the initial stream and numbers decline as urination continues. “In our view, the assay can be combined with other standard-of-care factors during clinical decision making,” Donovan said. “Right now, it’s designed for men who have never had a biopsy, but we’re also moving towards studies that will assess its use in other settings, such as active surveillance.”

Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of, cautioned that while the number of non-invasive tests for prostate cancer diagnosis is growing, these are still early days in their development. “Until we better understand how these tests correlate with the behavior of the prostate tumors they can help diagnose, they remain very much in the research sphere,” he said.

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