The Association of Urinary PCA3 and TMPRSS2:ERG with Biopsy-based Reclassification

The dilemma that resulted from the widespread use of serum prostate-specific androgen (PSA) testing was the identification of a significant number of men with indolent pure red cell aplasia (PrCa). After a significant period of overtreatment, the implementation of active surveillance (AS) has partly solved that issue. However, 25-50 % of AS patients will undergo an intervention. The follow up is rather invasive including serum PSA and repeat biopsies.

Models based on clinical parameters can be used to predict repeat biopsy outcome, yet improved methods to asses the risk to predict adverse pathology are needed. Candidate tools are improved imaging and biomarkers. In the past decade, molecular urine biomarkers were introduced in clinical practice (i.e.Prostate Cancer Gene 3 (PCA3) and TMPRSS2 erg).

Newcomb and colleagues studied the potential utility of these in the Canary Prostate Active Surveillance study (PASS). In this study, 24 % of patients were reclassified. PCA3 did add to the clinical model, albeit marginally (increase in AUC of 0,01), whereas TMPRSS2-erg did not. It should be noted that neither PCA3, nor TMPRSS2-ERG were identified as progression markers (i.e. being correlated with tumor aggressiveness); In fact, PCA3 expression is even negatively correlated with Gleason score. Furthermore, the performance of the clinical model is quite good (AUC = 0,743). So, studies, where progression markers are included with a stronger endpoint than biopsy outcome (e.g. histological outcome after radical prostatectomy), may provide a step forward in predicting biopsy outcome in AS patients.

Written by: Jack Schalken, Ph.D., Director of Urological Research, Professor of Experimental Urology, Radboud University MC, Nijmegen, Netherlands

Read the Full-Text Article: Performance of PCA3 and TMPRSS2:ERG urinary biomarkers in prediction of biopsy outcome in the Canary Prostate Active Surveillance Study (PASS)