Comparative Assessment of Urinary Prostate Cancer Antigen 3 and TMPRSS2:ERG Gene Fusion with the Serum [−2]Proprostate-Specific Antigen–Based Prostate Health Index for Detection of Prostate Cancer

Abstract

BACKGROUND We compared urinary prostate cancer antigen 3 (PCA3), transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG), and the serum [−2]proprostate-specific antigen ([−2]proPSA)-based prostate health index (Phi) for predicting biopsy outcome. METHODS Serum samples and first-catch urine samples were collected after digital rectal examination (DRE) from consented outpatients with PSA 0.5–20 μg/L who were scheduled for prostate biopsy. The PCA3 score (PROGENSA PCA3, Hologic Gen-Probe) and T2:ERG score (Hologic Gen-Probe) were determined. Measurements of serum PSA, free PSA, and [−2]proPSA (Beckman Coulter) were performed, and the percentages of free PSA (%fPSA) and Phi ([−2]proPSA/fPSA × √PSA) were determined. RESULTS Of 246 enrolled men, prostate cancer (PCa) was diagnosed in 110 (45%) and there was no evidence of malignancy (NEM) in 136 (55%). A first set of biopsies was performed in 136 (55%) of all men, and 110 (45%) had ≥1 repeat biopsies. PCA3, Phi, and T2:ERG differed significantly between men with PCa and NEM, and these markers showed the largest areas under the ROC curve (AUCs) (0.74, 0.68, and 0.63, respectively). PCA3 had the largest AUC of all parameters, albeit not statistically different from Phi. Phi showed somewhat lower specificities than PCA3 at 90% sensitivity. Combination of both markers enhanced diagnostic power with modest AUC gains of 0.01–0.04. Although PCA3 had the highest AUC in the repeat-biopsy cohort, the highest AUC for Phi was observed in DRE-negative patients with PSA in the 2–10 μg/L range. CONCLUSIONS PCA3 and Phi were superior to the other evaluated parameters but their combination gave only moderate enhancements in diagnostic accuracy for PCa at first or repeat prostate biopsy.

The Roles of Multiparametric Magnetic Resonance Imaging, PCA3 and Prostate Health Index—Which is the Best Predictor of Prostate Cancer after a Negative Biopsy?

“…6,23 To date 2 studies have reported on head-to-head comparisons between PCA3 and PHI to establish which test has the highest accuracy in predicting prostate cancer with RB. 7,8 In the first study the performance of the 2 biomarkers was compared in a cohort of 246 patients undergoing initial or repeat biopsy. 7 In the RB cohort the PCA3 results were more discriminating.…”

“…7,8 In the first study the performance of the 2 biomarkers was compared in a cohort of 246 patients undergoing initial or repeat biopsy. 7 In the RB cohort the PCA3 results were more discriminating. In the second study Scattoni et al evaluated the results of the 2 biomarkers in 95 patients who underwent RB.…”

The way of prostate cancer diagnostics

“…While prostate-specific antigen (PSA) remains the basic parameter, the additional value of the two 2012 FDA-approved biomarkers prostate health index (PHI) in serum and prostate cancer gene 3 (PCA3) in urine has been confirmed numerous times [1]. The detection of TMPRSS2-ERG gene fusions in the tissue of approximately 50% of all prostate cancer patients and the subsequently developed urinary assay [2] put hope on further diagnostic improvement that could unfortunately only be partially fulfilled [3][4][5].The senior author of this article [6] in this issue of Clinical Chemistry and Laboratory Medicine played the key role in detecting PCA3 and developing urinary assays for PCA3 and TMPRSS2-ERG [7]. And this group is now the first that compared both markers in whole urine, urinary sediment and exosomes.…”

“…While prostate-specific antigen (PSA) remains the basic parameter, the additional value of the two 2012 FDA-approved biomarkers prostate health index (PHI) in serum and prostate cancer gene 3 (PCA3) in urine has been confirmed numerous times [1]. The detection of TMPRSS2-ERG gene fusions in the tissue of approximately 50% of all prostate cancer patients and the subsequently developed urinary assay [2] put hope on further diagnostic improvement that could unfortunately only be partially fulfilled [3][4][5].…”

Thiosulfate in urine: new hope or new failure of a biomarker for prostate cancer?

“…Chwatko et al [11] did not incorporate the already mentioned new urinary biomarkers PCA3 and TMPRSS2:ERG in the study. In recent studies, especially PCA3 has been proven to be superior to PSA and percent free PSA [24,25]. Thus, a comparison of the clinical validity of thiosulfate with PCA3 and TMPRSS2:ERG in a cohort with similar PSA concentrations below 10 µg/L or at least < 20 µg/L would be necessary.…”