AR-V7 in Peripheral Whole Blood of Patients with Castration-resistant Prostate Cancer: Association with Treatment-specific Outcome Under Abiraterone and Enzalutamide

Abstract Background It has been demonstrated that androgen receptor splice variant 7 (AR-V7) expression in circulating tumor cells(CTCs) predicts poor treatment response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abirateroneor enzalutamide. Objective To develop a practical and robust liquid profiling approach for direct quantification of AR-V7 in peripheral whole bloodwithout the need for CTC capture and to determine its potential for predicting treatment response in mCRPC patients. Design, setting, and participants Whole bloodsamples from a prospective biorepositoryof 85 mCRPC patients before treatment initiation with abiraterone( n =56) or enzalutamide( n =29) were analyzed via droplet digital polymerase chain reaction. Outcome measurements and statistical analysis The association of AR-V7 status with prostate-specific antigen (PSA) response defined by PSA decline ≥50% and with PSA–progression-free survival (PSA-PFS), clinical PFS, and overall survival (OS) was assessed. Results and limitations High AR-V7 expression levels in whole bloodwere detectable in 18% (15/85) of patients. No patient with high AR-V7 expression achieved a PSA response, and AR-V7 status was an independent predictor of PSA response in multivariable logistic regression analysis ( p =0.03). High AR-V7 expression was associated with shorter PSA-PFS (median 2.4 vs 3.7 mo; p p p p p =0.02), and shorter OS (HR 3.0, 95% CI 1.4–6.3; p =0.005). Conclusions Testing of AR-V7 mRNA levels in whole bloodis a simple and promising approach to predict poor treatment outcome in mCRPC patients receiving abirateroneor enzalutamide. Patient summary We established a method for determining AR-V7 status in whole blood. This test predicted treatment resistance in patients with metastatic castration-resistant prostate cancer undergoing treatment with abirateroneor enzalutamide. Prospective validation is needed before application to clinical practice.