PD71-06 CTC-BASED GENE EXPRESSION FOR PREDICTING RESISTANCE TO ABIRATERONE AND ENZALUTAMIDE IN MCRPC

Abstract

You have accessJournal of UrologyProstate Cancer: Markers III1 Apr 2017PD71-06 CTC-BASED GENE EXPRESSION FOR PREDICTING RESISTANCE TO ABIRATERONE AND ENZALUTAMIDE IN MCRPC Jae-Seung Chung, Yugang Wang, Henderson James, Udit Singhal, Yuanyuan Qiao, Alexander Zaslavsky, Dan Hovelson, Felix Feng, Ganesch Palapattu, Taichman Russell, Arul Chinnaiyan, Scott Tomlins, and Todd Morgan Jae-Seung ChungJae-Seung Chung More articles by this author , Yugang WangYugang Wang More articles by this author , Henderson JamesHenderson James More articles by this author , Udit SinghalUdit Singhal More articles by this author , Yuanyuan QiaoYuanyuan Qiao More articles by this author , Alexander ZaslavskyAlexander Zaslavsky More articles by this author , Dan HovelsonDan Hovelson More articles by this author , Felix FengFelix Feng More articles by this author , Ganesch PalapattuGanesch Palapattu More articles by this author , Taichman RussellTaichman Russell More articles by this author , Arul ChinnaiyanArul Chinnaiyan More articles by this author , Scott TomlinsScott Tomlins More articles by this author , and Todd MorganTodd Morgan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3173AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There is a continued need to develop liquid biomarkers that predict response to 2nd generation hormonal therapies. While circulating tumor cell (CTC)-based detection of AR-V7 has been shown to be one potential marker, the apparent rarity of AR-V7 positivity is indicative of the importance of other drivers of resistance in this setting. We sought to utilize a multiplex gene expression platform for assessing CTCs in order to determine other potential predictive biomarkers of response to abiraterone and enzalutamide. METHODS Whole blood (~5mL) was obtained from 37 patients with metastatic castration resistant prostate cancer (mCRPC) starting enzalutamide (n=16) or abiraterone (n=21). CTCs were isolated using anti-EpCAM-conjugated magnetic beads, and following cell lysis, mRNA was extracted followed by multiplex qRT-PCR for 44 prostate cancer-related genes plus internal controls. Gene expression was normalized to controls, and samples were considered CTC-positive based on a previously established set of epithelial markers (EpCAM, EGFR, DSG2, KRT8, KRT18 and KRT19). The primary endpoint was PSA progression-free survival (PFS), with PSA progression defined as an increase of 25% or more above the nadir. Univariable Cox regression analyses were performed to assess for genes associated with PFS at false discovery rate (FDR) < 0.20. RESULTS We identified 27 (73%) patients with detectable CTCs among the 37mCRPC patients. The median age of the cohort was 73 years (IQR 64-78), and patients were followed for a median of 7.4 months (IQR 3.8-18.5). A total of 22 (81.5%) patients suffered PSA progression at a median time of 3.3 months (IQR 1.5-6.8). In the Cox analysis, PSMA (HR 3.83, 95%CI 1.62-9.03, p=0.002), TSPAN8 (HR 2.04, 95%CI 1.21-3.46, p=0.008), BMP7 (HR 1.46, 95%CI 1.09-1.95, p=0.017), and GAS6 (HR 2.29, 95%CI 1.16-4.51, p=0.017) were independent predictors of shorter PFS. CONCLUSIONS We identified four prostate cancer-related genes that can be identified in CTCs and appear to predict short PFS in men with mCRPC being treated with enzalutamide or abiraterone. While this is a small cohort and prospective validation is needed, these findings highlight the potential role for this approach in helping guide therapy choice. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1357 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Jae-Seung Chung More articles by this author Yugang Wang More articles by this author Henderson James More articles by this author Udit Singhal More articles by this author Yuanyuan Qiao More articles by this author Alexander Zaslavsky More articles by this author Dan Hovelson More articles by this author Felix Feng More articles by this author Ganesch Palapattu More articles by this author Taichman Russell More articles by this author Arul Chinnaiyan More articles by this author Scott Tomlins More articles by this author Todd Morgan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...