Non-Invasive Prostate Cancer Test Developed Using Exosomal RNA

The current screening paradigm for prostate cancer faces challenges that lead to unnecessary biopsies and, ultimately, overtreatment. The disadvantage of Prostate-Specific Antigen (PSA) testing is lack of specificity for prostate cancer resulting in both false positive and false negative results.

Furthermore, PSA does not discriminate between high- and low-grade prostate cancers. Low-grade disease could remain indolent for a long period of time and typically does not require aggressive treatment. There is a need for pre-biopsy diagnostic tools that can accurately identify high-grade prostate cancer that requires more immediate intervention.


A team of Urologists led by those at Columbia University (New York, NY, USA) used reverse-transcriptase polymerase chain reaction (PCR), to compare the urine exosome gene expression assay with biopsy outcomes in 499 patients with prostate-specific antigen (PSA) levels of 2 to 20 ng/mL. The derived prognostic score was then validated in 1,064 patients from 22 community practice and academic urology clinic sites in the USA. Eligible participants included indolent prostate cancer (PCA)-free men, 50 years or older, scheduled for an initial or repeated prostate needle biopsy due to suspicious digital rectal examination (DRE) findings and/or PSA levels (limit range, 2.0 to 20.0 ng/mL).

The teams used the novel urine-based prostate cancer liquid biopsy test, ExoDx Prostate(IntelliScore) (Exosome Diagnostics, Inc, Cambridge, MA, USA) in non-DRE, first-catch urine samples. The test then analyzes the urine for three biomarkers on exosomal ribonucleic acid (exoRNA) that are expressed in men with high-grade prostate cancer. In 255 men in the training target population (median age 62 years and median PSA level 5.0 ng/mL, and initial biopsy), the urine exosome gene expression assay plus standard of care (SOC) was associated with improved discrimination between Gleason score (GS7) or greater and GS6 and benign disease. Independent validation in 519 patients urine exosome gene expression assay plus SOC was superior to SOC. Using a predefined cut point, 138 of 519 (27%) biopsies would have been avoided, missing only 5% of patients with dominant pattern 4 high-risk GS7 disease.

James McKiernan, MD, the lead author said, “The possibility of a ‘liquid biopsy’ that does not involve an invasive procedure and may be as simple as a urine test, has the potential to change the way we approach the most common cancer in men. If the predictive accuracy of the assay can be validated in further studies, it has the potential to replace the PSA test once and for all.” The study was published on March 31, 2016, in the journal JAMA Oncology.

Related Links:
Columbia University
Exosome Diagnostics