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Eur Urol. 2014 Mar;65(3):534-42. doi: 10.1016/j.eururo.2012.11.014. Epub 2012 Nov 15.

Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer.

Author information

1
Radboud University Nijmegen Medical Centre, Department of Urology, Nijmegen, The Netherlands.
2
Noviogendix, Department of Research and Development, Nijmegen, The Netherlands.
3
ZGT Hospital, Department of Urology, Hengelo, The Netherlands.
4
AMC University Medical Centre, Department of Urology, Amsterdam, The Netherlands.
5
CWZ Hospital, Department of Urology, Nijmegen, The Netherlands.
6
St. Elisabeth Hospital, Department of Urology, Tilburg, The Netherlands.
7
Scheper Hospital, Department of Urology, Emmen, The Netherlands.
8
Radboud University Nijmegen Medical Centre, Department of Pathology, Nijmegen, The Netherlands.
9
Radboud University Nijmegen Medical Centre, Department of Urology, Nijmegen, The Netherlands. Electronic address: j.schalken@uro.umcn.nl.

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.

KEYWORDS:

PCA3; Prognostic; Prostate cancer; TMPRSS2-ERG; Urinary biomarkers

PMID:
23201468
DOI:
10.1016/j.eururo.2012.11.014
[Indexed for MEDLINE]

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