Abstract 899
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.
Resources from the same session
1500 - Retrospective evaluation of neutropenic admission events in metastatic or high-risk hormone-sensitive prostate cancer (HSPC) patients having docetaxel chemotherapy upfront or for castrate-resistant prostate cancer (CRPC) in STAMPEDE
Presenter: Harriet Mintz
Session: Poster Display session 3
Resources:
Abstract
3524 - Cabazitaxel For Octogenarian Patients With Metastatic Castration-Resistant Prostate Cancer (MCRPC).
Presenter: Paolo Tralongo
Session: Poster Display session 3
Resources:
Abstract
5637 - External Validation of a Prognostic Score in First-Line Metastastic Castration-Resistant Prostate Cancer (mCRPC)
Presenter: David Lorente
Session: Poster Display session 3
Resources:
Abstract
3228 - Treatment outcomes of 3rd treatment in a real-world metastatic castration resistant prostate cancer (mCRPC) population: results from the Dutch CAPRI-registry
Presenter: Jessica Notohardjo
Session: Poster Display session 3
Resources:
Abstract
4695 - Pelvic lymph node dissection and its extent on survival benefit in prostate cancer patients with a risk of lymph node invasion>5%: a propensity score matching analysis from SEER database
Presenter: Junru Chen
Session: Poster Display session 3
Resources:
Abstract
4438 - Multi-institutional evaluation of therapeutic management for oligometastatic cancer prostate recurrence with choline-PET/CT
Presenter: Morgane Guibert-broudic
Session: Poster Display session 3
Resources:
Abstract
4574 - Safety of new androgen receptor inhibitors (ARi) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC): a network meta-analysis of randomized controlled trials (RCT)
Presenter: Amelia Altavilla
Session: Poster Display session 3
Resources:
Abstract
3816 - Real-world use of radium-223 for treatment of metastatic castration resistant-prostate cancer (mCRPC): results from the Dutch CAPRI registry
Presenter: Malou Kuppen
Session: Poster Display session 3
Resources:
Abstract
5180 - A phase 2a study of radium-223 dichloride (Ra-223) alone or in combination with abiraterone acetate or enzalutamide in metastatic castration-resistant prostate cancer (mCRPC)
Presenter: Daniel Petrylak
Session: Poster Display session 3
Resources:
Abstract
1067 - Adding ADT to PSMA-PET/CT-guided SBRT for oligometastatic prostate cancer improves distant progression-free survival
Presenter: Carole Mercier
Session: Poster Display session 3
Resources:
Abstract