Sarah Buelens1, Tom Claeys2, Bert Dhondt3, Filip Poelaert3, Matthijs Vynck4, Nurten Yigit5, Olivier Thas6, Piet Ost7, Jo Vandesompele5, Nicolaas Lumen3, Candy Kumps2. 1. Department of Urology, Ghent University Hospital, Ghent, Belgium; Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent, Ghent University, Ghent, Belgium. Electronic address: sarah.buelens@uzgent.be. 2. Department of Urology, Ghent University Hospital, Ghent, Belgium. 3. Department of Urology, Ghent University Hospital, Ghent, Belgium; Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent, Ghent University, Ghent, Belgium. 4. Department of Data Analysis and Mathematical Modelling, Ghent University, Ghent, Belgium. 5. Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent, Ghent University, Ghent, Belgium; Center for Medical Genetics, Ghent University, Ghent, Belgium. 6. Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent, Ghent University, Ghent, Belgium; Department of Data Analysis and Mathematical Modelling, Ghent University, Ghent, Belgium; National Institute for Applied Statistics Research Australia, University of Wollongong, Wollongong, NSW, Australia. 7. Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent, Ghent University, Ghent, Belgium; Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium.
Abstract
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.
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.