When a blood test for prostate-specific antigen (PSA) returns an abnormal result, the next step is usually a prostate biopsy. A biopsy can confirm or rule out a cancer diagnosis, but it also has certain drawbacks. Prostate biopsies are invasive procedures with potential side effects, and they often detect low-grade, slow-growing tumors that may not require immediate treatment — or any treatment at all.
Researchers are studying several strategies to avoid unnecessary biopsies. Special magnetic resonance imaging (MRI) scans, for example, can be helpful in predicting whether a man’s tumor is likely to spread. A blood test called the Prostate Health Index (PHI) measures various forms of PSA and can help doctors determine whether a biopsy is needed.
In April, researchers at the University of Michigan published results from a test that checks urine samples for prostate cancer. The test, called MyProstateScore 2.0 (MPS2), looks for 18 different genes associated with high-grade tumors. “If this test is negative, it’s almost certain that you don’t have aggressive prostate cancer,” Dr. Arul Chinnaiyan, a professor of pathology and urology at the university, said in a news release.
Data collection and further testing
To develop the test, Dr. Chinnaiyan and his colleagues first drew on publicly available databases of over 58,000 genes associated with prostate cancer. From this initial pool, they narrowed the number down to 54 genes that are clearly overexpressed in cancers of grade group 2 (GG2) or higher. The grade group system ranks prostate cancer from GG1 (least dangerous) to GG5 (most dangerous).
The team tested these 54 genes using archived urine samples from 761 men with elevated PSA who were scheduled for biopsy. This effort identified 18 genes that consistently correlated with high-grade cancer in the biopsy samples. These genes now make up MPS2.
The team then validated the test by performing MPS2 testing on over 800 archived urine samples collected by a national prostate cancer research consortium. Other researchers affiliated with this consortium assessed the results of the new urine test using patient records.
Interpretation of results
The study results showed that MPS2 correctly identified 95% of prostate cancers that were GG2 and 99% of cancers that were GG3 or higher. Test accuracy was further improved by including estimates of prostate size (or volume, as it is also called).
The team calculated that using MPS2 would have reduced unnecessary biopsies by 37%. If volume had been included in the measurement, 41% of biopsies could have been avoided. By comparison, using the PHI would have avoided only 26% of biopsies.
Dr. Chinnaiyan and his co-authors emphasize that ruling out high-grade cancer with a urine test offers some advantages over MRI. The special multiparametric MRI scans needed to diagnose high-grade cancer in men with elevated PSA, for example, are not always available in community settings. In addition, interpretation of mpMRI results can vary from radiologist to radiologist. Importantly, the MPS2 can be updated over time as new prostate cancer genes are identified.
Comment
Dr. Boris Gershman, a urologist at Harvard-affiliated Beth Israel Deaconess Medical Center in Boston and a member of the advisory and editorial board of the Harvard Medical School Guide to Prostate Diseases, called the new study results promising. “It appears that the performance of the 18-gene urine test is better than that of PSA alone,” he says.
But Dr. Gershman adds that it will be important to consider how such a test fits into the current two-tiered approach to PSA screening, which involves a prostate MRI if the PSA is abnormal. Where the MRI provides a yes/no result (meaning lesions that look suspicious for cancer are either present or not), the MPS2 provides numerical risk estimates between 0% and 100%. “The challenge in clinically implementing a continuous risk score is where to draw the line for a biopsy,” says Dr. Gershman.
“This research is very encouraging, as many men in rural areas may not have access to prostate MRI machines or the additional complexity required to interpret these MRI scans,” says Dr. Marc Garnick, Gorman Brothers Professor ofMedicine at Harvard Medical School and Beth Israel Deaconess Medical Center. “A widely available urine test could ultimately help more accurately determine who should undergo a prostate biopsy and could also help estimate the likelihood that a cancer is clinically significant and requires treatment.”