Background:

New screening methods that can add predictive diagnostic value for aggressive (high-grade, Gleason score⩾ 7) prostate cancer (PCa) are needed to reduce unnecessary biopsies for patients with non-aggressive PCa. This is particularly important for men presenting for an initial biopsy with an equivocal PSA in the 2–10 ng ml− 1 range. PCA3 and ERG are biomarkers that can add predictive value for PCa in urine; however, with a limited utility as a digital rectal exam (DRE) is required.

Methods:

First-catch urine samples were collected at six sites from men scheduled to undergo a prostate biopsy. Exosomal RNA was extracted, RNA copy numbers of ERG and PCA3 were measured by reverse transcription–quantitative PCR (RT–qPCR), and the EXO106 score (the sum of normalized PCA3 and ERG RNA levels) was computed. Performance was compared with standard of care (SOC; PSA, age, race or family history) parameters. Contingency table, logistic regression, receiver operating characteristics curve and box-plot analyses were performed.

Results:

In this cohort (N= 195), a dichotomous EXO106 score demonstrated good clinical performance in predicting biopsy result for both any cancer and high-grade disease. For high-grade disease, the negative and positive predictive values were 97.5% and 34.5%, respectively. The discrimination between high-grade and Gleason score⩽ 6 (including benign) biopsy results by a combination of EXO106 and SOC (area under the curve (AUC)= 0.803) was significantly improved compared with SOC without EXO106 (AUC= 0.6723, P= 0.0009). The median EXO106 score correlated (P< 0.001; Spearman’s rank order) with histologic grade.

Conclusions:

A novel molecular signature (EXO106 score) derived from non-DRE urine demonstrated independent, negative predictive value for the diagnosis of high-grade PCa from initial biopsy for men with ‘gray zone’serum PSA levels. Its use in the biopsy decision process could result in fewer prostate biopsies for clinically insignificant disease.