Performance of a validated urine exosome gene expression test (EPI) in men within the USPSTF suggested age-group of 55 to 69 years at initial biopsy with a PSA 2-10 ng/mL.

Abstract

53 Background: Prostate-specific antigen (PSA) plays a key-role in prostate cancer (PCa) risk stratification but leads to over-diagnosis of low grade PCa. Recently, the USPSTF recommended that the decision to undergo PSA-based screening for men aged 55 to 69 years should be an individual one. We have developed and validated a non-invasive diagnostic test (ExoDx Prostate(IntelliScore), EPI) as a decision aid to guide the initial prostate biopsy decision process for men in the PSA gray zone of 2-10 ng/mL. The EPI test is a urine exosome gene expression assay to discriminate high-grade (GG 2) from low-grade (GG 1) and benign disease, thereby reducing the number of unnecessary biopsies. Methods: Patient data from two clinical trials were merged and constrained by age (55-69) according to the USPSTF suggested age-group resulting in a cohort of 701 patients with PSA 2-10 ng/mL, scheduled for initial prostate needle biopsy. EPI test results as well as PCPT2.0 risk calculator, ERSPC risk calculator and PSA results are compared with biopsy outcomes. Performances are reported using the area under the receiver operating characteristic curve (AUC), Negative predictive value (NPV), Positive predictive value (PPV), Sensitivity, and Specificity for discriminating ≥GG2 from GG1 and benign disease. Results: EPI showed a superior AUC of 0.70 compared to PSA (AUC: 0.57), PCPT2.0 (AUC: 0.60) and ERSPC (AUC: 0.58) (all p-values < 0.001) for discriminating ≥GG2 PCa from benign and GG1. The previously validated EPI cut-point of 15.6 would avoid 22% of all prostate biopsies and 29% of unnecessary biopsies, with an NPV of 93% and miss only 5.4% of ≥GG2, respectively. Conclusions: EPI is a non-invasive, easy to use urine exosome RNA expression assay to discriminate high-grade (GG2) from low-grade (GG1) PCa and benign disease. EPI significantly outperformed the other standard of care parameters tested and applying the EPI test for risk stratification of patients in the USPSTF suggested age group, should reduce the number of unnecessary biopsies.