New urine test improves detection of high-grade prostate cancer

A new type of urine test that detects RNA from genes associated with prostate cancer identified 92% of men with elevated prostate-specific antigen (PSA) levels who had high-grade cancers, according to a study published online March 31, 2016 in JAMA Oncology.

Researchers predict that the test could also reduce the diagnoses of low-risk prostate cancer for most men who present with a borderline PSA level, and this would result in fewer unnecessary biopsies.

“The test has the potential to be a significant improvement over PSA alone in distinguishing between low- and high-grade prostate cancer, especially in the PSA ‘gray zone’ patient,” said the study’s first author James McKiernan, MD, the John K. Lattimer Professor and Chair of Urology at Columbia University Medical Center and Urologist-in-Chief at NewYork-Presbyterian/Columbia, in New York, NY.

“It could reduce hundreds of thousands of invasive biopsies each year,” he added. “Given the pain and risks associated with performing a prostate biopsy, that’s not a trivial thing.”

The test—the ExoDx^TMProstate(IntelliScore), developed by Exosome Diagnostics of Cambridge, MA—detects RNA from three genes (ERG, PCA3, and SPDEF) linked to the development and progression of prostate cancer.

Although other blood- and urine-based assays also predict risk of high-grade prostate cancer at initial biopsy, this test is the only urine-based assay that doesn’t require a digital rectal exam or prostate massage prior to collection, and it’s easily integrated in the clinic environment, the researchers noted.

In 2012, the United States Preventive Services Task Force recommended against PSA screening for prostate cancer, citing overdiagnosis and overtreatment. But fewer screenings also means fewer opportunities to diagnose high-risk disease, in which treatment is proven to reduce deaths from prostate cancer, the researchers noted.

The only way to definitively diagnose prostate cancer is with a tissue biopsy, Dr. McKiernan said. “Consequently, men with high PSA levels are typically advised to have a biopsy, even though most have no cancer at all, or have a type of disease that can be monitored without treatment,” he said. “In other words, a lot of men are undergoing unnecessary biopsies.”

In this study, Dr. McKiernan and colleagues obtained prostate biopsy results from 774 men with PSA levels between 2 and 10 ng/mL, which represents most men undergoing PSA testing and prostate biopsy. The researchers then compared these data with a composite score based on results of the ExoDx urine test plus “standard of care,” which included PSA level, age, race, and family history of prostate cancer.

Using data from 255 of the men, the researchers first set a cut-off score of 15.6 that identified over 90% of men found to have high-grade cancer. The researchers then used this designated cut-off score to assess the test’s performance among the remaining 519 men. That is, a score above 15.6 was used to predict the presence of high-grade cancer (Gleason Score of 7 or greater), and a score equal to or below 15.6 was used to predict the presence of low-grade cancer or no disease.

The researchers found that the test correctly identified 92% of men with high-grade cancer. The test also predicted high-grade cancer in 66% of men whose biopsies revealed low-grade or no cancer. If used in clinical practice, the test would have spared 27% of men from having an unnecessary prostate biopsy.

Among the 138 men whose low test score predicted low-grade or no cancer, 91% had no cancer or low-grade cancer that didn’t require immediate treatment. “By adding this test to our evaluation, men who receive a low score could potentially choose to forgo a biopsy,” Dr. McKiernan said.

Of the 12 men who had high-grade cancer but a low test score, 9 had moderately aggressive cancer that would likely have been detected with follow-up monitoring, the researchers noted. The remaining 3 had a higher risk of cancer. “By missing less than 5% of patients with dominant GS4 disease, the assay was able to provide an overall net benefit when compared with standard clinical tools,” the authors wrote.

The investigators are now planning additional clinical trials to obtain FDA approval.

This study was funded by grants from Exosome Diagnostics.