ARV7 status and CTC count: A combined biomarker for the baseline therapeutic decision in each line of mCRPC treatment

Abstract

Background: Metastatic Castration Resistant Prostate Cancer (mCRPC) is an entity for which we have more than one therapeutic option. Chemotherapy and novel hormonal agents (NHAs) are the main choices. Despite clinical, biochemical, radiological and histologic parameters, we have not yet confirmed the ideal sequence of regimens. Since PSA is not enough to guide treatment selection in mCRPC, there is a need for a biomarker that would lead us to the ideal regimen choice in each line of therapy for each patient (pt) in order to transform mCRPC into a chronic disease. ARV7 status and circulating tumor cells (CTCs) have shown some potential as biomarkers the last 2 years. The aim of this study was to combine these two biomarkers as a parameter for selecting the optimal treatment strategy. We aimed to categorize mCRPC pts by combining ARV7 status and CTC count and correlating this with response to therapy and, consequently, regimen choice. Methods: CellSearch was used for CTC counts.We developed a highly sensitive and specific multiplex RT-qPCR assay in the LightCycler platform for the simultaneous quantification of AR splice variants (AR-FL, AR-V7, AR-567, AR-total) in CTCs. 41 pts and 57 samples were categorized in four groups: 1. CTChigh(h) (CTC count >10) ARV7+(14 samples) 2. CTClow(l) (CTCcount