Alexander Haese1, Geert Trooskens2, Sandra Steyaert2, Daphne Hessels2, Michael Brawer2, Virginie Vlaeminck-Guillem3,4, Alain Ruffion5,4, Derya Tilki6, Jack Schalken7, Jack Groskopf2, Wim Van Criekinge8. 1. Martini-Klinik Prostate Cancer Center , Hamburg , Germany. 2. MDxHealth, Inc. , Irvine , California. 3. Medical Unit of Molecular Oncology and Transfer, Department of Biochemistry and Molecular Biology, University Lyon Sud Hospital, Pierre Bénite , Lyon , France. 4. Cancer Research Centre of Lyon, U1052 INSERM, CNRS 5286, Claude Bernard University Lyon 1, Léon Bérard Centre , Lyon , France. 5. Urology Department, University Lyon Sud Hospital, Pierre Bénite , Lyon , France. 6. Department of Urology, University Hospital Hamburg-Eppendorf , Hamburg , Germany. 7. Department of Urology, Radboud University Medical Centre , Nijmegen , The Netherlands. 8. Department of Bioinformatics, Ghent University , Ghent , Belgium.
Abstract
PURPOSE: A 2-gene, urine based molecular test that combines mRNA biomarkers with clinical factors can risk stratify patients for clinically significant prostate cancer. To ensure the generalizability of assay results we optimized and validated the clinical model for men with serum prostate specific antigen less than 10 ng/ml who were undergoing initial prostate biopsy. MATERIALS AND METHODS: Urine samples were collected from 1,955 men from The Netherlands, France and Germany prior to an initial prostate biopsy and study subjects were divided into training and validation cohorts. Urinary HOXC6 and DLX1 mRNA levels were quantified and RNA results were then combined with other risk factors in a clinical model optimized to detect ISUP (International Society of Urological Pathology) Grade Group 2 or greater prostate cancer in men with prostate specific antigen less than 10 ng/ml. Results in the validation cohort were compared with the PCPTRC (Prostate Cancer Prevention Trial Risk Calculator), version 2.0. RESULTS: The optimal clinical model included urinary HOXC6 and DLX1 mRNA levels, patient age, digital rectal examination and prostate specific antigen density (serum prostate specific antigen/prostate volume). In the 715 validation cohort subjects with prostate specific antigen less than 10 ng/ml the AUC was 0.82 with 89% sensitivity, 53% specificity and 95% negative predictive value. The PCPTRC AUC was 0.70. The full validation cohort of 916 men including all prostate specific antigen levels yielded an AUC of 0.85 with 93% sensitivity, 47% specificity and 95% negative predictive value. The PCPTRC AUC was 0.76. CONCLUSIONS: The 2-gene based urine assay, which is optimized for biopsy naïve patients with serum prostate specific antigen less than 10 ng/ml, demonstrated high sensitivity and negative predictive value to detect clinically significant prostate cancer. These data support using the test to help guide initial prostate biopsy decisions.
PURPOSE: A 2-gene, urine based molecular test that combines mRNA biomarkers with clinical factors can risk stratify patients for clinically significant prostate cancer. To ensure the generalizability of assay results we optimized and validated the clinical model for men with serum prostate specific antigen less than 10 ng/ml who were undergoing initial prostate biopsy. MATERIALS AND METHODS: Urine samples were collected from 1,955 men from The Netherlands, France and Germany prior to an initial prostate biopsy and study subjects were divided into training and validation cohorts. Urinary HOXC6 and DLX1 mRNA levels were quantified and RNA results were then combined with other risk factors in a clinical model optimized to detect ISUP (International Society of Urological Pathology) Grade Group 2 or greater prostate cancer in men with prostate specific antigen less than 10 ng/ml. Results in the validation cohort were compared with the PCPTRC (Prostate Cancer Prevention Trial Risk Calculator), version 2.0. RESULTS: The optimal clinical model included urinary HOXC6 and DLX1 mRNA levels, patient age, digital rectal examination and prostate specific antigen density (serum prostate specific antigen/prostate volume). In the 715 validation cohort subjects with prostate specific antigen less than 10 ng/ml the AUC was 0.82 with 89% sensitivity, 53% specificity and 95% negative predictive value. The PCPTRC AUC was 0.70. The full validation cohort of 916 men including all prostate specific antigen levels yielded an AUC of 0.85 with 93% sensitivity, 47% specificity and 95% negative predictive value. The PCPTRC AUC was 0.76. CONCLUSIONS: The 2-gene based urine assay, which is optimized for biopsy naïve patients with serum prostate specific antigen less than 10 ng/ml, demonstrated high sensitivity and negative predictive value to detect clinically significant prostate cancer. These data support using the test to help guide initial prostate biopsy decisions.
Entities:
Keywords:
RNA; biopsy; messenger; prostate specific antigen; prostatic neoplasms; risk
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