Objectives: To investigate if full-length androgen receptor (AR-FL) is associated with resistance to androgen receptor (AR)-directed therapy independently and/or combined with AR splice variant 7 (AR-V7). Patients and Methods: Plasma samples were prospectively collected from 73 patients with castrate-resistant prostate cancer before first- or second-line AR-directed therapy. mRNA was isolated from exosomes and AR-FL and AR-V7 were analysed by droplet digital PCR. Results: AR-FL was detected in all patients and 22% of them were AR-V7-positive at baseline. AR-FL expression was significantly higher in AR-V7-positive vs AR-V7-negative patients (P < 0.0001). After stratifying patients by tertile for AR-FL expression, progression-free survival (PFS) was 22 vs 18 vs 4 months for lower vs intermediate vs higher tertile, respectively (P = 0.0003). The median PFS and overall survival were significantly longer in AR-V7-negative vs AR-V7-positive patients (20 vs 4 months, P < 0.0001; not reached vs 9 months, P < 0.0001, respectively). Conclusions: Resistance to AR-directed therapy was associated with the presence of AR-V7; however, AR-FL expression may help better refine response and survival of patients to AR-directed therapy. Both biomarkers, if validated in prospective trials, could be used to select the best treatment strategy.

Additional Metadata
Keywords #PCSM, #ProstateCancer, AR-directed therapy, AR-FL, AR-V7, castrate-resistant prostate cancer, predictive biomarkers
Persistent URL dx.doi.org/10.1111/bju.14792, hdl.handle.net/1765/120252
Journal BJU International
Citation
Del Re, M, Crucitta, S. (Stefania), Sbrana, A. (Andrea), Rofi, E, Paolieri, F. (Federico), Gianfilippo, G. (Giulia), … Danesi, R. (2019). Androgen receptor (AR) splice variant 7 and full-length AR expression is associated with clinical outcome: a translational study in patients with castrate-resistant prostate cancer. BJU International, 124(4), 693–700. doi:10.1111/bju.14792