Division of Urology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.Harvard Medical School, Boston, MA 02215, USA.
We sought to develop a clinical algorithm combining serum PSA with detection of TMPRSS2:ERG fusion and CaP3 in urine collected after digital rectal exam (post-DRE urine) to predict prostate cancer on subsequent biopsy.
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 CaP3 and TMPRSS2:ERG fusion transcript expression. Serum PSA was measured by clinical assay. The performance of TMPRSS2:ERG fusion, CaP3, and serum PSA as biomarkers predicting prostate cancer at biopsy was measured; a clinically practical algorithm combining serum PSA with TMPRSS2:ERG and CaP3 in post-DRE urine to predict prostate cancer was developed.
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). CaP3 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 CaP3 and 0.72 for serum PSA alone). Combining serum PSA, CaP3, and TMPRSS2:ERG in a multivariable algorithm optimized for clinical utility improved cancer prediction (AUC = 0.88; specificity = 90% at 80% sensitivity).
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 CaP3 or TMPRSS2:ERG in post-DRE urine, performed better than the individual biomarkers alone in predicting prostate cancer.
Salami SS, Schmidt F, Laxman B, Regan MM, Rickman DS, Scherr D, Bueti G, Siddiqui J, Tomlins SA, Wei JT, Chinnaiyan AM, Rubin MA, Sanda MG. Are you the author?
Reference: Urol Oncol. 2011 May 18. Epub ahead of print.