Autor: |
Erdmann K; Department of Urology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.; National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01307 Dresden, Germany.; German Cancer Consortium (DKTK), Partner Site Dresden, 01307 Dresden, Germany and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Distler F; Department of Urology, Nuremberg General Hospital, Paracelsus Medical University, 90419 Nuremberg, Germany., Gräfe S; Department of Urology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.; National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01307 Dresden, Germany., Kwe J; Department of Urology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany., Erb HHH; Department of Urology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.; German Cancer Consortium (DKTK), Partner Site Dresden, 01307 Dresden, Germany and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Fuessel S; Department of Urology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.; German Cancer Consortium (DKTK), Partner Site Dresden, 01307 Dresden, Germany and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Pahernik S; Department of Urology, Nuremberg General Hospital, Paracelsus Medical University, 90419 Nuremberg, Germany., Thomas C; Department of Urology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.; National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01307 Dresden, Germany., Borkowetz A; Department of Urology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.; German Cancer Consortium (DKTK), Partner Site Dresden, 01307 Dresden, Germany and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. |
Abstrakt: |
Serum prostate-specific antigen (PSA), its derivatives, and magnetic resonance tomography (MRI) lack sufficient specificity and sensitivity for the prediction of risk reclassification of prostate cancer (PCa) patients on active surveillance (AS). We investigated selected transcripts in urinary extracellular vesicles (uEV) from PCa patients on AS to predict PCa risk reclassification (defined by ISUP 1 with PSA > 10 ng/mL or ISUP 2-5 with any PSA level) in control biopsy. Before the control biopsy, urine samples were prospectively collected from 72 patients, of whom 43% were reclassified during AS. Following RNA isolation from uEV, multiplexed reverse transcription, and pre-amplification, 29 PCa-associated transcripts were quantified by quantitative PCR. The predictive ability of the transcripts to indicate PCa risk reclassification was assessed by receiver operating characteristic (ROC) curve analyses via calculation of the area under the curve (AUC) and was then compared to clinical parameters followed by multivariate regression analysis. ROC curve analyses revealed a predictive potential for AMACR, HPN, MALAT1, PCA3, and PCAT29 (AUC = 0.614-0.655, p < 0.1). PSA, PSA density, PSA velocity, and MRI maxPI-RADS showed AUC values of 0.681-0.747 ( p < 0.05), with accuracies for indicating a PCa risk reclassification of 64-68%. A model including AMACR, MALAT1, PCAT29, PSA density, and MRI maxPI-RADS resulted in an AUC of 0.867 ( p < 0.001) with a sensitivity, specificity, and accuracy of 87%, 83%, and 85%, respectively, thus surpassing the predictive power of the individual markers. These findings highlight the potential of uEV transcripts in combination with clinical parameters as monitoring markers during the AS of PCa. |