AUTHOR=Gurioli Giorgia , Conteduca Vincenza , Lolli Cristian , Schepisi Giuseppe , Gargiulo Stefania , Altavilla Amelia , Casadei Chiara , Scarpi Emanuela , De Giorgi Ugo 

TITLE=Plasma AR Copy Number Changes and Outcome to Abiraterone and Enzalutamide

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.567809

DOI=10.3389/fonc.2020.567809

ISSN=2234-943X

ABSTRACT=<p><bold>Introduction:</bold> Plasma androgen receptor (<italic>AR</italic>) copy number (CN) status identifies castration-resistant prostate cancer (CRPC) patients with worse outcome on abiraterone/enzalutamide. However, the impact of <italic>AR</italic> CN changes on clinical outcome in CRPC is unknown.</p><p><bold>Materials and Methods:</bold> Plasma samples from 73 patients treated with abiraterone or enzalutamide were collected at baseline and at the time of progression disease (PD). Droplet digital polymerase chain reaction was used to assess <italic>AR</italic> CN status.</p><p><bold>Results:</bold> We showed that 11 patients (15.1%) changed <italic>AR</italic> CN status from baseline to PD (9 patients from normal to gain, 2 from gain to normal). Patients changing <italic>AR</italic> CN status from normal at baseline to gain at PD had intermediate median overall survival (OS) of 20.5 months (95% CI = 8.0–44.2) between those who remained <italic>AR</italic> CN normal from baseline to PD (27.3 months [95% CI = 21.9–34.4]) and those who remained <italic>AR</italic> CN gain from baseline to PD (9.1 months [95% CI = 3.8–14.5], <italic>p</italic> &lt; 0.0001). Patients changing <italic>AR</italic> CN from normal at baseline to gain at PD had a median progression-free survival (PFS) of 9.2 months (95% CI = 2.0–14.7), patients who remained <italic>AR</italic> CN normal had a median PFS of 9.1 months (95% CI = 7.2–10.1), and patients who remained <italic>AR</italic> CN gain had a median PFS of 5.4 (95% CI = 3.6–6.5, <italic>p</italic> = 0.0005). Both OS and PFS were not significantly different between patients with <italic>AR</italic> CN that changes from normal to gain and patients with stable <italic>AR</italic> CN normal.</p><p><bold>Conclusions:</bold> We showed that CRPC patients changing <italic>AR</italic> CN status from baseline to progression time point had intermediate OS and we suggested that <italic>AR</italic> CN evaluation at baseline could be the most informative for clinical outcome of CRPC patients treated with abiraterone or enzalutamide. Larger prospective studies are warranted.</p>