Validation of a 2‐gene mRNA urine test for the detection of ≥GG2 prostate cancer in an opportunistic screening population

Background 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