doi:10.1002/pros.23964engRubio-Briones, J.Borque-Fernando, A.Esteban, L.M.Mascarós, J.M.Ramírez-Backhaus, M.Casanova, J.Collado, A.Mir, C.Gómez-Ferrer, A.Wong, A.Aragón, F.Calatrava, A.López-Guerrero, J.A.Groskopf, J.Schalken, J.Van Criekinge, W.Domínguez-Escrig, J.Validation of a 2-gene mRNA urine test for the detection of =GG2 prostate cancer in an opportunistic screening populationART-2020-117176Background: A 2-gene urine-based molecular test that targets messenger RNAs known to be overexpressed in aggressive prostate cancer (PCa) has been described as a helpful method for detecting clinically significant prostate cancer (grade group [GG] =2). We performed an external validation of this test in men undergoing initial prostate biopsy (Bx) within a Spanish opportunistic screening scenario. Methods: We analyzed archived samples from 492 men who underwent prostate Bx in an opportunistic screening scenario, with prostate-specific antigen (PSA) 3 to 10 ng/mL and/or suspicious digital rectal exploration (DRE) and without previous multi-parametric magnetic resonance imaging (mpMRI). Urinary biomarker measurements were combined with clinical risk factors to determine a risk score, and accuracy for GG = 2 PCa detection was compared with PCA3, European randomized screening in prostate cancer (ERSPC), and prostate biopsy collaborative group (PBCG) risk calculators in a validation workup that included calibration, discrimination, and clinical utility analysis. Results: In our cohort, the detection rates for GG1 and GG = 2 PCa were 20.3% and 14.0%, respectively. The median PSA level was 3.9 ng/mL and 13.4% of subjects had suspicious DRE findings. The median risk score for men with GG = 2 PCa was 21 (interquartile range: 14-28), significantly higher than benign+GG1 PCa (10, 6-18), P <.001, achieving the highest area under the curve among the models tested, 0.749 (95% confidence interval: 0.690-0.807). The urine test was well-calibrated, while ERSPC showed a slight underestimation and PBCG a slight overestimation of risk. Assuming a GG2 non-detection rate of 11% without using mpMRI, use of the urinary biomarker-based clinical model could have helped avoid 37.2% of excess biopsies while delaying the diagnosis of eight patients (1.6% of the entire cohort) with GG = 2 PCa. Conclusions: In this first evaluation in an opportunistic screening population, the urinary biomarker-based test improved the detection of clinically significant PCa. Facing men with elevated PSA and/or suspicious DRE, it could be a useful tool to help avoid excess initial Bx and to identify patients most likely to benefit from Bx.2020http://zaguan.unizar.es/record/13044910.1002/pros.23964http://zaguan.unizar.es/record/130449oai:zaguan.unizar.es:130449PROSTATE 80, 6 (2020), 500-507All rights reservedhttp://www.europeana.eu/rights/rr-f/info:eu-repo/semantics/closedAccess