Prognostic and therapeutic implications of circulating androgen receptor gene copy number in prostate cancer patients using droplet digital polymerase chain reaction

Abstract

Because resistance mechanisms in the androgen receptor (AR) pathway remain key drivers of progression, we assessed the AR gene copy number (CN) gain in a general population (n = 100) and its implications in prostate cancer. AR CN gain was found to be a promising biomarker anticipating faster progression to castration-resistant prostate cancer (CRPC), a poor prognosis, and worse abiraterone and enzalutamide outcomes in CRPC.Background: Resistance mechanisms in the androgen receptor (AR) signaling pathway remain key drivers in the progression to castration-resistant prostate cancer (CRPC) and relapse under antihormonal therapy. Materials and Methods: We evaluated the circulating AR gene copy number (CN) gain using droplet digital polymerase chain reaction in 21 control and 91 prostate cancer serum samples and its prognostic and therapeutic implications in prostate cancer. Results: In CRPC, AR CN gain was associated with faster progression to CRPC (P = .026), a greater number of previous treatments (P = .045), and previous chemotherapy (P = .016). Comparing patients with and without CN gain, the median progression-free survival (PFS) in the abiraterone subgroup was 1.7 months versus not reached (P = .004), and the median overall survival (OS) was 7 months versus 20.9 months (P = .020). In the enzalutamide subgroup, PFS was 1.7 versus 10.8 months (P = .006), and OS was 6.1 versus 16.5 months (P = .042). In the taxane subgroup, PFS was 3.2 versus 6.5 months (P = .093), and OS was 3.9 months versus not reached (P = .026). The presence of more AR copies correlated with shorter androgen deprivation (P = .002), abiraterone (P = .022), enzalutamide (P = .008), and taxane (P = .039) therapy. Conclusion: Circulating AR CN gain predicts for a poor prognosis in CRPC. It is a promising biomarker predetermining rapid CRPC progression and predicting worse abiraterone and enzalutamide outcomes. Furthermore, it is associated with multiple previous treatments and previous chemotherapy. (C) 2017 Elsevier Inc. All rights reserved.