Abstract
BackgroundInitial prostate biopsy often fails to identify prostate cancer resulting in patient anxiety, especially when clinical features such as prostate specific antigen (PSA) remain elevated, leading to the need for repeat biopsies. Prostate biomarker tests, such as the ExoDx™ Prostate (IntelliScore), or EPI test, have been shown to provide individualized risk assessment of clinically significant prostate cancer at initial biopsy; however, the performance in the repeat biopsy setting is not well established.MethodsAs part of a previous prospective clinical validation study evaluating the performance of the EPI test, we collected first-catch, non-DRE urine samples across 22 sites from men with at least one prior negative biopsy scheduled to undergo a repeat prostate biopsy to rule out prostate cancer. All men were 50 years or older with a PSA 2–10 ng/mL. Exosomal mRNA was extracted and expression of three genomic markers, PCA3, ERG and SPDEF was measured. The resulting EPI score was correlated with biopsy results.Results229 men with a prior negative biopsy underwent repeat biopsies. ExoDx Prostate demonstrated good performance ruling out high-grade (Grade group 2, GG2, or higher) prostate cancer (HGPCa) using the previously validated 15.6 cut point in the initial biopsy setting. The EPI test yielded an NPV of 92% independent of other clinical features and would have avoided 26% of unnecessary biopsies while missing only five patients with HGPCa (2.1%). Furthermore, the EPI test provided additional information at a cut-point of 20 and 29.6 with an NPV of 94%, potentially delaying 35 and 61% of unnecessary biopsies, respectively. AUC curves and Net Health Benefit Analyses demonstrated superior performance of ExoDx Prostate over PSA and clinical only risk calculators, i.e. ERSPC.ConclusionsThe EPI test provided good performance using the 15.6 cut-point for ruling out HGPCa / GG2 or higher in men undergoing a repeat prostate biopsy with a PSA of 2–10 ng/ml. Furthermore, the test utilizes gene expression data independent of clinical features to predict the likelihood of HGPCa / GG2 on a subsequent needle biopsy.
Highlights
Initial prostate biopsy often fails to identify prostate cancer resulting in patient anxiety, especially when clinical features such as prostate specific antigen (PSA) remain elevated, leading to the need for repeat biopsies
Prostate needle biopsies are typically recommended for men with elevated serum PSA levels and/or a suspicious digital rectal exam (DRE) with added considerations based on family history, age, and race
Study population First-catch, non-DRE urine samples were collected at 22 clinical sites in the USA from men with a prior negative prostate biopsy scheduled for a repeat biopsy between June 2014 and April 2015
Summary
Initial prostate biopsy often fails to identify prostate cancer resulting in patient anxiety, especially when clinical features such as prostate specific antigen (PSA) remain elevated, leading to the need for repeat biopsies. Prostate biomarker tests, such as the ExoDxTM Prostate (IntelliScore), or EPI test, have been shown to provide individualized risk assessment of clinically significant prostate cancer at initial biopsy; the performance in the repeat biopsy setting is not well established. A large percentage of newly diagnosed prostate cancers are indolent, clinically insignificant, and with low metastatic potential. These cancers typically do not require definitive treatment and may be managed most effectively with Active Surveillance (AS). For each negative initial biopsy, it is unknown whether elevated PSA levels and/or a suspicious DRE facilitated the biopsy decision or if the biopsy missed a cancerous lesion due to sampling error, tumor heterogeneity and multifocality [12]
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