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

Rubio-Briones, J. ; Borque-Fernando, A. (Universidad de Zaragoza) ; 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.

Resumen: 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 <.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.

Idioma: Inglés

DOI: 10.1002/pros.23964

Año: 2020

Publicado en: PROSTATE 80, 6 (2020), 500-507
ISSN: 0270-4137

Factor impacto JCR: 4.104 (2020)

Categ. JCR: UROLOGY & NEPHROLOGY rank: 23 / 89 = 0.258 (2020) - Q2 - T1
Categ. JCR: ENDOCRINOLOGY & METABOLISM rank: 69 / 144 = 0.479 (2020) - Q2 - T2

Factor impacto SCIMAGO: 1.294 - Urology (Q1) - Oncology (Q1)

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Urología (Dpto. Cirugía)