Urine exosome gene expression assay net benefit analysis in a large pooled cohort.

Abstract

287 Background: Over-diagnosis of indolent prostate cancer (PCa), supports the need for non-invasive tools that can differentiate low-grade (≤ Gleason score 6, GS 6) from high-grade (≥ GS 7). We examined the clinical benefit of ExoDx™ Prostate (IntelliScore) (EPI) results in a pooled cohort over a range of probabilities using net benefit analysis. Methods: A pooled dataset of two prior validation cohorts and additional cases from a large group practice provided a large data set (N=1,212) for net benefit analysis. The pooled population consisted of men > 50 years, scheduled for initial biopsy and with a PSA measurement. Urine specimens were collected at enrollment using a provided urine collection device and the EPI tests were run at a CLIA-certified central laboratory at Exosome Diagnostics, Waltham, MA. The clinical decision value of the urine exosome gene expression assay (EPI) was assessed using net benefit analysis and compared EPI results with standard of care information across a range of probabilities for which a patient might decide on a prostate biopsy. The net benefit is determined by adding the true positive results and subtracting the false negatives across different biopsy probability thresholds. Results: The ExoDx IntelliScore or EPI assay (green) demonstrated superior clinical benefit when compared to the Prostate Cancer Prevention Trial (PCPT) prostate cancer risk calculator or PSA. Conclusions: In this new analysis of a large pooled cohort, the EPI exosome gene expression assay had the highest clinical net benefit across the 10% - 50% decision threshold compared to decision support methods currently used in the clinic.