Predicting high-grade prostate cancer at initial biopsy: clinical performance of the ExoDx (EPI) Prostate Intelliscore test in three independent prospective studies.

BACKGROUND: The ability to discriminate indolent from clinically significant prostate cancer (PC) at the initial biopsy remains a challenge. The ExoDx Prostate (IntelliScore) (EPI) test is a noninvasive liquid biopsy that quantifies three RNA targets in urine exosomes. The EPI test stratifies patients for risk of high-grade prostate cancer (HGPC; ≥ Grade Group 2 [GG] PC) in men ≥ 50 years with equivocal prostate-specific antigen (PSA) (2-10 ng/mL). Here, we present a pooled meta-analysis from three independent prospective-validation studies in men presenting for initial biopsy decision. METHODS: Pooled data from two prospective multi-site validation studies and the control arm of a clinical utility study were analyzed. Performance was evaluated 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 pathology. RESULTS: The combined cohort (n = 1212) of initial-biopsy subjects had a median age of 63 years and median PSA of 5.2 ng/mL. The EPI AUC (0.70) was superior to PSA (0.56), Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) (0.62), and The European Randomized Study of Screening for Prostate Cancer (ERSPC) (0.59), (all p-values <0.001) for discriminating GG2 from GG1 and benign histology. The validated cutoff of 15.6 would avoid 23% of all prostate biopsies and 30% of "unnecessary" (benign or Gleason 6/GG1) biopsies, with an NPV of 90%. CONCLUSIONS: EPI is a noninvasive, easy-to-use, urine exosome-RNA assay that has been validated across 3 independent prospective multicenter clinical trials with 1212 subjects. The test can discriminate high-grade (≥GG2) from low-grade (GG1) cancer and benign disease. EPI effectively guides the biopsy-decision process independent of PSA and other standard-of-care factors.