Validation of a urine- based proteomics test to predict clinically significant prostate cancer: complementing MRI pathway

medRxiv

Abstract

Abstract Purpose Prostate cancer (PCa) is the most frequently diagnosed cancer in men. One major clinical need is to accurately predict clinically significant PCa (csPCa). A proteomics based 19-biomarker model (19-BM) was previously developed using Capillary Electrophoresis-Mass Spectrometry (CE-MS) and validated in 1000 patients at risk for PCa. Here, our objective was to validate 19-BM in a multicentre prospective cohort of 101 biopsy-naive patients using current diagnostic pathways. Materials and Methods Urine samples from 101 PCa patients were analysed through CE-MS. All patients underwent MRI using a 3-T system. The 19-BM score was estimated via a support vector machine-based software (MosaCluster; v1.7.0), employing previously established cut-off criterion of -0.07. Previously developed diagnostic nomograms were calculated along with MRI. Results Independent validation of the 19-BM yielded a sensitivity of 77% and specificity of 85% (AUC:0.81). This performance surpasses that of PSA (AUC:0.56), and PSA density (AUC:0.69). For PI-RADS≤ 3 patients, the 19-BM showed a sensitivity of 86% and specificity of 88%. Integrating the 19-BM with MRI resulted in significantly better accuracy (AUC:0.90) compared to the individual investigations alone (AUC 19BM =0.81; p=0.004 and AUC MRI :0.79; p=0.001). Examining the decision curve analysis, the 19-BM with MRI surpassed other approaches for the prevailing risk interval from 30% cut-off. Conclusions 19-BM exhibited favourable reproducibility for prediction of csPCa. In PI-RADS≤3 patients the 19-BM correctly classified 88% of the patients with insignificant PCa at the cost of one csPCa patient that was missed. Utilising 19-BM test could prove valuable complementing MRI and reducing the need for unnecessary biopsies.

Authors 15

1. Maria Frantzi

   Mosaiques Diagnostics and Therapeutics (Germany)

   Affiliation as printed

   Mosaiques diagnostics GmbH, Department of Biomarker Research, Hannover, Germany

2. Ana C. Morillo

   Instituto Maimónides de Investigación Biomédica de Córdoba · Hospital Universitario Reina Sofía · University of Córdoba

   Affiliation as printed

   Reina Sofía University Hospital, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), University of Cordoba (UCO), Department of Urology, Cordoba, Spain

3. Guillermo Lendinez

   Hospital Universitario Virgen del Rocío · Instituto de Biomedicina de Sevilla

   Affiliation as printed

   Virgen del Rocio University Hospital, IBIS, Department of Urology, Seville Spain

4. Ana Blanca

   Instituto Maimónides de Investigación Biomédica de Córdoba · Hospital Universitario Reina Sofía · University of Córdoba

   Affiliation as printed

   Reina Sofía University Hospital, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), University of Cordoba (UCO), Department of Urology, Cordoba, Spain

5. Daniel López Ruiz

   Instituto Maimónides de Investigación Biomédica de Córdoba · Hospital Universitario Reina Sofía · University of Córdoba

   Affiliation as printed

   Reina Sofía University Hospital, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), University of Cordoba (UCO), Department of Radiology, Cordoba, Spain

6. Jose Parada

   Hospital Universitario Virgen del Rocío · Instituto de Biomedicina de Sevilla

   Affiliation as printed

   Virgen del Rocio University Hospital, IBIS, Department of Radiology, Seville Spain

7. Isabel Maria Heidegger

   Innsbruck Medical University · Universität Innsbruck

   Affiliation as printed

   Medical University of Innsbruck, Department of Urology, Innsbruck, Austria

8. Zoran Čulig

   Innsbruck Medical University · Universität Innsbruck

   Affiliation as printed

   Medical University of Innsbruck, Department of Urology, Innsbruck, Austria

9. Emmanouil Mavrogeorgis Aachen Institute for Molecular Cardiovascular Research

   RWTH Aachen University · Universitätsklinikum Aachen · Mosaiques Diagnostics and Therapeutics (Germany)

   Affiliation as printed

   Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University Hospital, 52074 Aachen, Germany

   Mosaiques diagnostics GmbH, Department of Biomarker Research, Hannover, Germany

   Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University Hospital, 5204 Aachen, Germany

10. Antonio López-Beltrán

    University of Córdoba

    Affiliation as printed

    University of Cordoba, Department of Pathology, Cordoba, Spain

11. Marina Mora-Ortiz

    Instituto Maimónides de Investigación Biomédica de Córdoba · Hospital Universitario Reina Sofía · University of Córdoba

    Affiliation as printed

    Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofía University Hospital, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), University of Cordoba (UCO), Cordoba, Spain

12. Julia Carrasco‐Valiente

    Instituto Maimónides de Investigación Biomédica de Córdoba · Hospital Universitario Reina Sofía · University of Córdoba

    Affiliation as printed

    Reina Sofía University Hospital, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), University of Cordoba (UCO), Department of Urology, Cordoba, Spain

13. Harald Mischak

    University of Glasgow · Mosaiques Diagnostics and Therapeutics (Germany)

    Affiliation as printed

    Mosaiques diagnostics GmbH, Department of Biomarker Research, Hannover, Germany

    University of Glasgow, Institute of Cardiovascular and Medical Science, Glasgow, United Kingdom

14. Juan Pablo Campos Hernández

    Instituto Maimónides de Investigación Biomédica de Córdoba · Hospital Universitario Reina Sofía · University of Córdoba

    Affiliation as printed

    Reina Sofía University Hospital, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), University of Cordoba (UCO), Department of Urology, Cordoba, Spain

15. Enrique Gómez‐Gómez corresponding

    Instituto Maimónides de Investigación Biomédica de Córdoba · Hospital Universitario Reina Sofía · University of Córdoba

    Affiliation as printed

    Reina Sofía University Hospital, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), University of Cordoba (UCO), Department of Urology, Cordoba, Spain