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

作者：Seitz Anna Katharina; Thoene Silvia; Bietenbeck Andreas; Nawroth Roman; Tauber Robert; Thalgott Mark; Schmid Sebastian; Secci Ramona; Retz Margitta; Gschwend Juergen E; Ruland Juergen; Winter Christof; Heck Matthias M

来源：European Urology, 2017, 72(5): 828-834.

DOI：10.1016/j.eururo.2017.07.024

• Androgen receptor splice variant
• Resistance
• Castration-resistant prostate cancer
• Liquid profiling
• Droplet digital polymerase chain reaction

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 abiraterone or enzalutamide.
Objective: To develop a practical and robust liquid profiling approach for direct quantification of AR-V7 in peripheral whole blood without the need for CTC capture and to determine its potential for predicting treatment response in mCRPC patients.
Design, setting, and participants: Whole blood samples from a prospective biorepository of 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 blood were detectable in 18% (15/85) of patients. No patient with high AR-V7 expression achieved a PSA response, and AR-V7 statuswas an independent predictor of PSA response in multivariable logistic regression analysis (p = 0.03). High AR-V7 expression was associated with shorter PSAPFS (median 2.4 vs 3.7 mo; p < 0.001), shorter clinical PFS (median 2.7 vs 5.5 mo; p < 0.001), and shorter OS (median 4.0 vs. 13.9 mo; p < 0.001). On multivariable Cox regression analysis, high AR-V7 expression remained an independent predictor of shorter PSA-PFS (hazard ratio [HR] 7.0, 95% confidence interval [CI] 2.3-20.7; p < 0.001), shorter clinical PFS (HR 2.3, 95% CI 1.1-4.9; 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 blood is a simple and promising approach to predict poor treatment outcome in mCRPC patients receiving abiraterone or 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 abiraterone or enzalutamide. Prospective validation is needed before application to clinical practice.

• 出版日期2017-11