AR-V7 in peripheral whole blood of patients with castration-resistant prostate cancer: association with treatment-specific outcome under abiraterone and enzalutamide
AK Seitz, S Thoene, A Bietenbeck, R Nawroth… - European urology, 2017 - Elsevier
AK Seitz, S Thoene, A Bietenbeck, R Nawroth, R Tauber, M Thalgott, S Schmid, R Secci…
European urology, 2017•ElsevierBackground 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 …
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 …
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 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 < 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.
Elsevier
