title: Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer.
abstract: OBJECTIVE
  We sought to develop a clinical algorithm combining serum PSA with detection of TMPRSS2:ERG fusion and PCA3 in urine collected after digital rectal exam (post-DRE urine) to predict prostate cancer on subsequent biopsy.
  
  
  METHODS
  Post-DRE urine was collected in 48 consecutive patients before prostate biopsy at 2 centers; quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect PCA3 and TMPRSS2:ERG fusion transcript expression. Serum PSA was measured by clinical assay. The performance of TMPRSS2:ERG fusion, PCA3, and serum PSA as biomarkers predicting prostate cancer at biopsy was measured; a clinically practical algorithm combining serum PSA with TMPRSS2:ERG and PCA3 in post-DRE urine to predict prostate cancer was developed.
  
  
  RESULTS
  Post-DRE urine sediment provided informative RNA in 45 patients; prostate cancer was present on subsequent biopsy in 15. TMPRSS2:ERG in post-DRE urine was associated with prostate cancer (OR = 12.02; P < 0.001). PCA3 had the highest sensitivity in predicting prostate cancer diagnosis (93%), whereas TMPRSS2:ERG had the highest specificity (87%). TMPRSS2:ERG had the greatest discriminatory value in predicting prostate cancer (AUC = 0.77 compared with 0.65 for PCA3 and 0.72 for serum PSA alone). Combining serum PSA, PCA3, and TMPRSS2:ERG in a multivariable algorithm optimized for clinical utility improved cancer prediction (AUC = 0.88; specificity = 90% at 80% sensitivity).
  
  
  CONCLUSIONS
  A clinical algorithm specifying biopsy for all patients with PSA ≥ 10 ng/ml, while restricting biopsy among those with PSA <10 ng/ml to only those with detectable PCA3 or TMPRSS2:ERG in post-DRE urine, performed better than the individual biomarkers alone in predicting prostate cancer.
authors: Division of Urology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors: Simpa S
authors: SS
authors: Salami
authors: Folke
authors: F
authors: Schmidt
authors: Bharathi
authors: B
authors: Laxman
authors: Meredith M
authors: MM
authors: Regan
authors: David S
authors: DS
authors: Rickman
authors: Douglas
authors: D
authors: Scherr
authors: Gerardina
authors: G
authors: Bueti
authors: Javed
authors: J
authors: Siddiqui
authors: Scott A
authors: SA
authors: Tomlins
authors: John T
authors: JT
authors: Wei
authors: Arul M
authors: AM
authors: Chinnaiyan
authors: Mark A
authors: MA
authors: Rubin
authors: Martin G
authors: MG
authors: Sanda
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