AR-V7 in Peripheral Whole Blood of Patients with Castration-resistant Prostate Cancer: Association with Treatment-specific Outcome Under Abiraterone and Enzalutamide
Androgen receptor splice variant 7 (AR-V7) expression in circulating tumor cells (CTCs) was demonstrated to predict poor treatment response in metastatic castrationresistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide.
To develop a practical and robust liquid profiling approach for direct quantification of AR-V7 in peripheral whole blood without the need of CTC capturing and to determine its potential to predict 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 with droplet digital PCR.
Outcome measurement and statistical analyses
The association of AR-V7 status with prostate-specific antigen (PSA) response defined by PSA decline ≥50% as well as 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 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 months, p<0.001), shorter clinical PFS (median 2.7 vs. 5.5 months, p<0.001), and shorter OS (median 4.0 vs. 13.9 months, 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% 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).
AR-V7 mRNA level testing in whole blood is a simple and promising approach to predict poor treatment outcome in mCRPC patients undergoing treatment with abiraterone or enzalutamide.
In this report 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.