Combining Serum Prostate Health Index With Urinary PCA3 and TMPRSS2:ERG RNA Testing Improves Detection of Clinically Significant Prostate Cancer.

Purpose: We sought to determine whether combining prostate health index (Phi) with urinary prostate cancer antigen 3 (PCA3) and TMPRSS2:ERG (T2:ERG) could improve selection of men for prostate biopsy. These biomarkers have been validated in prostate cancer (PCa) detection separately, but their combination has not previously been developed. Materials and Methods: Prebiopsy blood and post-digital rectal examination urine specimens were assayed to predict subsequent biopsy outcomes from training and validation cohorts (1073 participants across 11 academic centers). Clinical algorithms for combining Phi and PCA3-T2:ERG to predict Grade Group ≥ 2 (GG ≥ 2) PCa were formulated using the training cohort (N = 512). Prediction rules and hypotheses were locked before validation using biopsy-naïve men from the NCI Early Detection Research Network urinary PCA3 trial (N = 561). Rules were compared in weighted sum of specificity and sensitivity with weights specified a priori, and Results: Primary validation analysis showed that Phi combined with urinary PCA3 outperformed Phi alone ( Conclusions: Combining serum Phi with urinary PCA3 RNA alone or together with urinary T2:ERG RNA, simultaneously or sequentially, improves selection of men for initial prostate biopsy and represents an avenue to improve early detection of aggressive PCa.