EURURO Vol. 72 No. 5

828 860

Prostate Cancer
AR-V7 in Peripheral Whole Blood of Patients with
Castration-resistant Prostate Cancer: Association with
Treatment-specific Outcome Under Abiraterone and Enzalutamide
Anna Katharina Seitz [3_TD$DIFF] Silvia Thoene [4_TD$DIFF] Andreas Bietenbeck Roman Nawroth
Robert Tauber Mark Thalgott Sebastian Schmid Ramona Secci Margitta Retz
Ju¨rgen E. Gschwend Ju¨rgen Ruland Christof Winter [1_TD$DIFF] [5_TD$DIFF] Matthias M. Heck
a Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Germany; bInstitute of Clinical Chemistry and Pathobiochemistry,
Klinikum rechts der Isar, Technical [7_TD$DIFF]University [8_TD$DIFF]of Munich, Munich, Germany; c German Cancer Consortium,[9_TD$DIFF] partner site Munich, Germany; dGerman Cancer
Research Center, Heidelberg, Germany; e Current address: Department of Urology, University Hospital of Würzburg, Germany.
available at
journal homepage:
Article info
Article history:
Accepted July 20, 2017
Associate Editor:
Giacomo Novara
Statistical Editor:
Andrew Vickers
Keywords:
Androgen receptor splice variant
Resistance
Castration-resistant prostate
cancer
Liquid profiling
Droplet digital polymerase chain
reaction
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 abirater-
one or enzalutamide.
Objective: To develop a practical and robust liquid profiling approach for direct quanti-
fication 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 bioreposi-
tory 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 inwhole 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%[15_TD$DIFF] CI 1.4–6.3; p = 0.005).
y These authors contributed equally to this work.
z These authors share senior authorship.
** Corresponding author. Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der
Isar, Technical University of Munich, Ismaninger Strasse 22, 81675 Munich, Germany.
Tel. +49 89 41404765.
E-mail address: (C. Winter).
* Corresponding author. Department of Urology, Klinikum rechts der Isar, Technical University of
Munich, Ismaninger Strasse 22, 81675 Munich, Germany. Tel. +49 89 41402520;
Fax: +49 89 41404843.
E-mail address: (M.M. Heck).
0302-2838/© 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.