899 - Urine extracellular vesicle GATA2 mRNA alone and in a multigene test predicts initial prostate biopsy result

Background

Prostate specific antigen (PSA) detection in blood is widely used to screen for prostate cancer (PCa). However, PSA has limited utility in discriminating high risk tumors (Gleason score≥7) from indolent-low risk tumors, which leads to unnecessary biopsies and highlights the need to identify better biomarkers for the detection of clinically significant PCa. GATA2 is a pioneer transcription factors which expression is increased in high-risk prostate cancer (PCa), but its utility in discriminating for PCa remains untested.

Methods

To determine whether extracellular vesicle (EV) GATA2 mRNA provides clinically relevant information to distinguish PCa, we prospectively analyzed non-digital rectal exam (DRE) urine EV GATA2 mRNA levels from 165 males with suspicion of PCa prior to biopsy and correlated GATA2 levels alone and combined in a multigene (PCA3 and TMPRSS2) EV mRNA assay to biopsy result.

Results

Prostate origin of GATA2 mRNA detected in urine EVs was confirmed by observing that GATA2 mRNA levels significantly dropped after prostatectomy (p < 0.05) and positively correlated to PCa tissue GATA2 mRNA levels. GATA2 increased in biopsy-positive PCa patients (p < 0.0001) and high-grade disease (p < 0.01). Multivariable analysis showed that GATA2 is an independent predictive factor of any cancer and high-grade PCa. GATA2 alone and combined in a multigene test with PCA3 and TMPRSS2-ERG (GAPT-E) improved discrimination of any cancer (GAPT-E1) and high-grade cancer (GAPT-E2): standard of care (SOC) area under the curve (AUC) of 0.62 and 0.65, SOC plus GATA2 AUC of 0.68 and 0.69, and SOC plus GAPT-E (1-2) AUC of 0.75 and 0.75, respectively. A GAPT-E1 cut-point of 57 would avoid 25.6% of unnecessary prostate biopsies and 13.7% of total biopsies with NPV 50% and missing 9% of PCa. Limitations include lack of PCa volume and imaging assessment of the cohort.

Conclusions

Non-DRE urine EV GATA2 mRNA alone and in combination with other urine EV biomarkers in men with suspicion of PCa provides useful information to distinguish any cancer and high-risk PCa and may reduce the number of biopsies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

NCI/NIH.

Disclosure

K. Yadav: Full / Part-time employment: SEMA4. A. Tewari: Research grant / Funding (self): Boston Scientific Corporation, Medtronic, Inc. (10/15/2013); Licensing / Royalties: DNA Based Bicistronic Vectors with Inducible and Constitutive Promoters - ID#: 160608, High Intensity Focus Ultrasound and CPG-Brachyury-siRNA for Treatment of Prostate Cancer - ID# 160403, Patent for a Catheterless Device and Approach, Uretheral Catheter; Leadership role: Global Prostate Cancer Research Foundation, Kalyani Prostate Cancer Institute, Peter Georgescu Foundation Award, Promaxo; Advisory / Consultancy: Roivant, Siemens. W.K. Kelly: Advisory / Consultancy: Sanofi, Foundation Medicine; Travel / Accommodation / Expenses: Janssen Oncology; Honoraria (self): Janssen Oncology, Constellation Pharmaceuticals; Research grant / Funding (institution): Sanofi, Novartis, Janssen Oncology, Bayer, Exelixis, Seattle Genetics, Endocyte. B.E. Leiby: Advisory / Consultancy: Bayer. L. Gomella: Honoraria (self), Advisory / Consultancy: Astellas/Janssen/Mdx Health/Strand; Research grant / Funding (self): FKD; Licensing / Royalties: Jefferson IP. All other authors have declared no conflicts of interest.