Validation of a CE-IVD, urine exosomal RNA expression assay for risk assessment of prostate cancer prior to biopsy

Abstract

Improved risk stratification of patients suspected of prostate cancer prior to biopsy continues to be an unmet clinical need. ExoDx Prostate (IntelliScore) “EPI” is a non-invasive urine test utilizing RNA from exosomes to provide a risk score that correlates with the likelihood of finding high grade prostate cancer at biopsy. Here, we present the results from a prospective clinical validation study of EPI-CE, a CE-marked in-vitro diagnostic (IVD) assay, specifically developed for use in European clinical laboratories. The study (NCT04720599) enrolled patients with ≥ 50 years, PSA 2–10 ng/mL, prior to MRI, who were scheduled for initial biopsy. First catch urine samples were collected from participants without prior digital rectal examination or prostate massage. Exosomal RNA was isolated and expression levels of three biomarkers ERG, PCA3 and SPDEF were analyzed according to the EPI-CE Instructions For Use. In the study cohort of N = 109 patients, EPI-CE was validated to have a Negative Predictive Value of 89%, a Sensitivity of 92% and a superior performance to two commonly used multiparametric risk calculators (PCPT and ERSPC) in both Receiver Operating Characteristics with a higher Area Under the Curve for EPI-CE 0.67 (95% CI 0.56–0.77) versus PCPT 0.59 (95% CI 0.47–0.71) and ERSPC 0.60 (95% CI 0.49–0.72) and higher Net Benefits analysis across a wide range of risk acceptance levels. This is the first clinical study reporting on the performance of EPI-CE. We demonstrate that EPI-CE provides information beyond standard clinical parameters and provides a better risk assessment prior to MRI, of patients suspected of prostate cancer, than the commonly used multiparametric risk calculators.

Liquid Biopsy in Prostate Cancer Management—Current Challenges and Future Perspectives

“…In addition, gene expression signature from urine exosomes also demonstrated a reliable clinically relevant predictive role (NPV 91.0%) in the decision making of patients with negative histological results [64]. Interestingly, the EPI urine biomarker was significantly associated with low-risk disease, making it a good test to select patients for AS [101].…”

Recent Advances in Blood-Based Liquid Biopsy Approaches in Prostate Cancer

“…Publications with the highest level of evidence were selected for review. This yielded 60 articles for which full text evaluation was performed and included in the final review 12–71 . A flow diagram of the article evaluation process is shown in Figure 1.…”

“…In a small cohort, Pang et al 70 showed that size-exclusion chromatography-based methods provided purer populations of EVs compared with precipitation methods in blood for PCa diagnosis. Notably, the ExoDx Prostate (IntelliScore) test based on EV detection of long noncoding and gene fusion RNAs in urine has been shown to aid detection of high-risk disease 66,67 Likewise, when performed before repeat biopsies in men with previous negative biopsies, the ExoDx test could predict high-risk disease in the repeat biopsy setting 64 . In other assays, plasma EVs positive for the protein STEAP1 had significant biomarker potential for detection/diagnosis but carried little prognostic information 69 .…”

Molecular mechanisms and clinical applications of exosomes in prostate cancer

“…The combination of ADSV and TGM4 can be used to distinguish benign tumors from malignant prostate tumors. The ExoDx Prostate IntelliScore from Exosome Diagnostics, which is based on the detection of ERG, PCA3, and SPDEF RNA in urinary exosomes, can be used to distinguish high-grade PC from low-grade PC and benign disease, and the combination of five proteins (i.e., CD63, GLPK5, SPHM, PSA, and PAPP) able to serve a similar purpose [ 168 , 170 , 171 ]. Furthermore, the semen exosome-based PSA/miR-142-3p/miR-142-5p/miR-223-3p model has shown potential for improving PC diagnostic/prognostic efficiency [ 169 ].…”