A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy.

IMPORTANCE Overdiagnosis and overtreatment of indolent prostate cancer (PCA) is a serious health issue in most developed countries. There is an unmet clinical need for noninvasive, easy to administer, diagnostic assays to help assess whether a prostate biopsy is warranted. OBJECTIVE To determine the performance of a novel urine exosome gene expression assay (the ExoDx Prostate IntelliScore urine exosome assay) plus standard of care (SOC) (ie, prostate-specific antigen [PSA] level, age, race, and family history) vs SOC alone for discriminating between Gleason score (GS)7 and GS6 and benign disease on initial biopsy. DESIGN, SETTING, AND PARTICIPANTS In training, using reverse-transcriptase polymerase chain reaction (PCR), we compared 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 1064 patients from 22 community practice and academic urology clinic sites in the United States. Eligible participants included 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, 2.0-20.0 ng/mL). MAIN OUTCOMES AND MEASURES Evaluate the assay using the area under receiver operating characteristic curve (AUC) in discrimination of GS7 or greater from GS6 and benign disease on initial biopsy. RESULTS 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 SOC was associated with improved discrimination between GS7 or greater and GS6 and benign disease: AUC 0.77 (95% CI, 0.71-0.83) vs SOC AUC 0.66 (95% CI, 0.58-0.72) (P < .001). Independent validation in 519 patients' urine exosome gene expression assay plus SOC AUC 0.73 (95% CI, 0.68-0.77) was superior to SOC AUC 0.63 (95% CI, 0.58-0.68) (P < .001). 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. CONCLUSIONS AND RELEVANCE This urine exosome gene expression assay is a noninvasive, urinary 3-gene expression assay that discriminates high-grade (≥GS7) from low-grade (GS6) cancer and benign disease. In this study, the urine exosome gene expression assay was associated with improved identification of patients with higher-grade prostate cancer among men with elevated PSA levels and could reduce the total number of unnecessary biopsies.