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

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


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.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / urine*
  • Biomarkers / urine
  • Gene Fusion
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / urine*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / urine*
  • Trans-Activators / genetics
  • Trans-Activators / urine*
  • Transcriptional Regulator ERG


  • Antigens, Neoplasm
  • Biomarkers
  • ERG protein, human
  • Trans-Activators
  • Transcriptional Regulator ERG
  • prostate cancer antigen 3, human
  • Serine Endopeptidases
  • TMPRSS2 protein, human