49 Background: Overdetection and overtreatment of indolent prostate cancer (PCa) remains a significant health issue requiring noninvasive assays to guide the prostate biopsy decision process. We demonstrated that a urine exosome gene expression assay (ExoDx P rostate ( I ntelliScore) (EPI) discriminates GS 7 PCa from GS 6 and benign disease, potentially reducing the number of unnecessary biopsies. The International Society of Urological Pathology (ISUP) proposed a prognostic PCa grading system to accurately reflect the biology of PCa; ISUP separates GS 7 PCa into group 2 (GS 3+4) and group 3 (GS 4+3). We sought to evaluate the performance of the EPI test according to the newly proposed ISUP system. Methods: The 519 patient validation cohort was re-annotated using ISUP and assessed benign (B) +/- ISUP 1 and B+ISUP 1+2 (GS 3+3, GS 3+4) from ISUP 3-5 (GS >= 4+3). We used validated / adjusted cut-points to assess performance with the AUC, sensitivity, specificity and NPV. In addition, we investigated the association of the EPI score with the benign biopsies (BB) and ISUP groups in the combined training and test cohort (n=774). Results: Applying the adjusted cut point (EPI 20) on the 519 ISUP cohort discriminated benign biopsies (BB) + ISUP 1 from >/=ISUP 2, 37% of biopsies avoided, NPV of 90%, equivalent to Gleason grading. Utilizing either the validated (15.6) or adjusted cut points on BB+ISUP 1+ 2 vs. >/=ISUP 3 (dominant pattern 4), 26% vs 37% biopsies avoided, with an improved NPV 98%. In the combined training / test cohort, higher EPI scores were significantly associated with ISUP categories. In this analysis EPI in BB vs. all ISUP groups (p<0.0001); BB+ISUP 1 vs. >/= ISUP2 (p<0.0001) and BB+ISUP 1+2 vs. >/=ISUP3 (p<0.0001); supporting accurate discrimination in high grade PCa. Conclusions: The EPI test is a noninvasive, first-catch non-DRE gene expression assay that accurately discriminates low-grade from high-grade PCa in both ISUP as well as Gleason score based grading systems. The test has the potential to reduce the number of unnecessary biopsies and performs equally well in contemporary approaches to PCa stratification.
The factors predicting upgrading of prostate cancer by using International Society for Urological Pathology (ISUP) 2014 Gleason grading system
