Abstract
BackgroundThe 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.MethodsPooled 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.ResultsThe 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%.ConclusionsEPI 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.
Highlights
Prostate cancer (PC) is the most common cancer in men and the second cause of cancer-related death in the United States
As mentioned in the National Comprehensive Cancer Network (NCCN) 2020 Prostate Cancer Early Detection guidelines, nearly 20 million men in the United States will engage in PC early detection discussions due to anxiety associated with fluctuating prostate-specific antigen (PSA) levels, a positive family history, and race
PSA and age were comparable across all studies, there was a 8% increase in the positive biopsy rate from the first to third validation study (48–56%), a 3% increase received a urine-collection container and shipping kits; men from the first validation study had received a pediatric urine cup with instructions to only collect urine within the requested volume range, while a standardized 20-mL volume-restricted vessel was used in the second validation cohort and the utility study
Summary
Prostate cancer (PC) is the most common cancer in men and the second cause of cancer-related death in the United States. Since PSA is not a reliable biomarker for the identification of clinically significant Grade Group 2 (GG2) and higher disease, there will continue to be a large percentage of men with either benign biopsies or clinically indolent, low-volume GG1 PC in addition to men with a more advanced stage. This cycle will result in a high fraction of men experiencing procedures such as surgery, radiation, or additional biopsies as part of an activesurveillance program [1,2,3,4,5,6]. There have been improvements in the prostate biopsy process—including the use of prophylactic antibiotics—the procedure is not entirely benign and rare complications may result, including an infection rate of 3–5% with the potential for emergency-room visits and hospitalizations [7]
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