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

Alexander Kretschmer, Holger Kajau, Eric Margolis, Ronald Tutrone, Tobias Grimm, Matthias Trottmann, Christian Stief, Georg Stoll, Christian A Fischer, Claudia Flinspach, Anja Albrecht, Lisa Meyer, Tina Priewasser, Daniel Enderle, Romy Müller, Phillipp Torkler, Jason Alter, Johan Skog, Mikkel Noerholm, Alexander Kretschmer, Holger Kajau, Eric Margolis, Ronald Tutrone, Tobias Grimm, Matthias Trottmann, Christian Stief, Georg Stoll, Christian A Fischer, Claudia Flinspach, Anja Albrecht, Lisa Meyer, Tina Priewasser, Daniel Enderle, Romy Müller, Phillipp Torkler, Jason Alter, Johan Skog, Mikkel Noerholm

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.

Conflict of interest statement

G.S., C.A.F., C.F., A.A., L.M., D.E., R.M., P.T., J.A., J.S. and M.N. are employees of Exosome Diagnostics. All other authors declare not conflict of interest.

© 2022. The Author(s).

Figures

Figure 1
Figure 1
Waterfall plot of all individual subjects in the study, ranked by EPI score and colored by biopsy pathology outcome. The black horizontal line represents the 15.6 cut-point.
Figure 2
Figure 2
Receiver-Operating-Characteristics Curve and Decision Curve/Net Benefit analysis of EPI-CE compared to PSA and the two multiparametric risk calculators, PCPT and ERSPC, showing that the EPI-CE score provides a higher Area-Under-Curve (AUC) and a higher Net Benefit than either of the multivariate risk calculators across a wide range of risk acceptance levels.

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