Urine TMPRSS2:ERG Plus PCA3 for Individualized Prostate Cancer Risk Assessment

Abstract

Background TMPRSS2:ERG (T2:ERG) and prostate cancer antigen 3 (PCA3) are the most advanced urine-based prostate cancer (PCa) early detection biomarkers. Objective Validate logistic regression models, termed Mi-Prostate Score (MiPS), that incorporate serum prostate-specific antigen (PSA; or the multivariate Prostate Cancer Prevention Trial risk calculator version 1.0 [PCPTrc]) and urine T2:ERG and PCA3 scores for predicting PCa and high-grade PCa on biopsy. Design, setting, and participants T2:ERG and PCA3 scores were generated using clinical-grade transcription-mediated amplification assays. Pretrained MiPS models were applied to a validation cohort of whole urine samples prospectively collected after digital rectal examination from 1244 men presenting for biopsy. Outcome measurements and statistical analysis Area under the curve (AUC) was used to compare the performance of serum PSA (or the PCPTrc) alone and MiPS models. Decision curve analysis (DCA) was used to assess clinical benefit. Results and limitations Among informative validation cohort samples (n = 1225 [98%], 80% from patients presenting for initial biopsy), models incorporating T2:ERG had significantly greater AUC than PSA (or PCPTrc) for predicting PCa (PSA: 0.693 vs 0.585; PCPTrc: 0.718 vs 0.639; both p < 0.001) or high-grade (Gleason score >6) PCa on biopsy (PSA: 0.729 vs 0.651, p < 0.001; PCPTrc: 0.754 vs 0.707, p = 0.006). MiPS models incorporating T2:ERG score had significantly greater AUC (all p < 0.001) than models incorporating only PCA3 plus PSA (or PCPTrc or high-grade cancer PCPTrc [PCPThg]). DCA demonstrated net benefit of the MiPS_PCPTrc (or MiPS_PCPThg) model compared with the PCPTrc (or PCPThg) across relevant threshold probabilities. Conclusions Incorporating urine T2:ERG and PCA3 scores improves the performance of serum PSA (or PCPTrc) for predicting PCa and high-grade PCa on biopsy. Patient summary Incorporation of two prostate cancer (PCa)-specific biomarkers (TMPRSS2:ERG and PCA3) measured in the urine improved on serum prostate-specific antigen (or a multivariate risk calculator) for predicting the presence of PCa and high-grade PCa on biopsy. A combined test, Mi-Prostate Score, uses models validated in this study and is clinically available to provide individualized risk estimates.

What are the New Developments in Urinary, Serum and Tissue Biomarkers in Prostate Cancer?

“…Bu skorla gereksiz biyopsilerden kaçınılırken prostat kanseri için daha iyi bir risk sınıflaması yapılabilmektedir. Bu test yaklaşık 2000 idrar örneği ile valide edilmiştir (9,42,43).…”

The context of prostate cancer genomics in personalized medicine

“…The HOXC6 and DLX1 homeobox genes are upregulated in prostate cancer cells and their expression increases during the progression of cancer to a higher-grade, castration-resistant and metastatic stage (55,56). The Mi-Prostate Score combined the expression signatures of urine ERG-TMPRSS2 and PCA3 with serum PSA, may improve the prediction of cancer risk and high-grade cancer following biopsy (57). A novel urine exosome 3-gene expression assay, which includes sterile alpha motif pointed domain, ERG and PCA3, may distinguish high-grade tumors (GS, ≥7) from low-risk (GS, ≤6) and benign disease when combined with standard factors (58).…”

The way of prostate cancer diagnostics

“…Despite a clear clinical usefulness of PCA3 [10] its limitations are the relative complicated measurement procedure and the low sensitivity at high values of > 100 [11]. However, the combination of PCA3 and TMPRSS2-ERG scores within several PSAbased models improved the predicting of PCa and highgrade PCa [5]. But it should be noted that the PCA3 and TMPRSS2-ERG-based Michigan-Prostate Score (MiPS) has costs of ~750 $.…”

“…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].…”