Title: | Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer |
Author(s): | Leyten, G.H.J.M.; Hessels, D. ; Jannink, S.A. ; Smit, F.P. ; Jong, H. de ; Cornel, E.B. ; Reijke, T.M. de; Vergunst, H.; Kil, P.; Knipscheer, B.C. ; Oort, I.M. van ; Mulders, P.F.A. ; Hulsbergen-van de Kaa, C.A. ; Schalken, J.A. |
Publication year: | 2014 |
Source: | European Urology, vol. 65, iss. 3, (2014), pp. 534-542 |
ISSN: | 0302-2838 |
DOI: | https://doi.org/10.1016/j.eururo.2012.11.014 |
Publication type: | Article / Letter to editor |
Please use this identifier to cite or link to this item : http://hdl.handle.net/2066/136611 ![]() |
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Subject: | Radboudumc 15: Urological cancers RIMLS: Radboud Institute for Molecular Life Sciences |
Organization: | Urology Paediatrics Pathology |
Journal title: |
European Urology
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Volume: | vol. 65 |
Issue: | iss. 3 |
Page start: | p. 534 |
Page end: | p. 542 |
Abstract: |
BACKGROUND: Prostate cancer antigen 3 (PCA3) and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG) gene fusions are promising prostate cancer (PCa) specific biomarkers that can be measured in urine. OBJECTIVE: To evaluate the diagnostic and prognostic value of Progensa PCA3 and TMPRSS2-ERG gene fusions (as individual biomarkers and as a panel) for PCa in a prospective multicentre setting. DESIGN, SETTING, AND PARTICIPANTS: At six centres, post-digital rectal examination first-catch urine specimens prior to prostate biopsies were prospectively collected from 497 men. We assessed the predictive value of Progensa PCA3 and TMPRSS2-ERG (quantitative nucleic acid amplification assay to detect TMPRSS2-ERG messenger RNA [mRNA]) for PCa, Gleason score, clinical tumour stage, and PCa significance (individually and as a marker panel). This was compared with serum prostate-specific antigen and the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculator. In a subgroup (n=61) we evaluated biomarker association with prostatectomy outcome. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariate and multivariate logistic regression analysis and receiver operating curves were used. RESULTS AND LIMITATIONS: Urine samples of 443 men contained sufficient mRNA for marker analysis. PCa was diagnosed in 196 of 443 men. Both PCA3 and TMPRSS2-ERG had significant additional predictive value to the ERSPC risk calculator parameters in multivariate analysis (p<0.001 and resp. p=0.002). The area under the curve (AUC) increased from 0.799 (ERSPC risk calculator), to 0.833 (ERSPC risk calculator plus PCA3), to 0.842 (ERSPC risk calculator plus PCA3 plus TMPRSS2-ERG) to predict PCa. Sensitivity of PCA3 increased from 68% to 76% when combined with TMPRSS2-ERG. TMPRSS2-ERG added significant predictive value to the ERSPC risk calculator to predict biopsy Gleason score (p<0.001) and clinical tumour stage (p=0.023), whereas PCA3 did not. CONCLUSIONS: TMPRSS2-ERG had independent additional predictive value to PCA3 and the ERSPC risk calculator parameters for predicting PCa. TMPRSS2-ERG had prognostic value, whereas PCA3 did not. Implementing the novel urinary biomarker panel PCA3 and TMPRSS2-ERG into clinical practice would lead to a considerable reduction of the number of prostate biopsies.
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