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.
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
PSA response to chemotherapy or NHAs was studied for each group, as well as duration of treatment and change of pt classification in groups. In each group, pts were categorized according to treatment type (chemotherapy, NHAs) and PSA responses were categorized as PSA decline or not. Group 1 pts did not appear to respond to NHAs but only to chemotherapy and had a worse prognosis compared to all other groups; pts in group 2 appeared to have an excellent and long term response to NHAs, though if chemo was received they also responded equally to both treatment options and had a better prognosis compared to all other groups; pts in group 3 responded better to chemotherapy than NHAs (though not excluding NHAs as a treatment choice); pts in group 4 responded to chemo and not NHAs.
Pts CTCl and ARV7- could safely be treated with NHAs while CTCl and ARV7+ pts could be treated with either chemotherapy or NHAs, with chemotherapy probably being a “safer” choice (less PSA non responses 1/8 vs 3/6). ARV7+ status does not seem to be an exclusion criteria alone for NHAs used in this category. For CTCh pts, chemotherapy is the best choice especially when pts are ARV7+. Since CTC and ARV7 status can change, these could be used as the baseline biomarker for regimen choice.
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All authors have declared no conflicts of interest.