Expression of androgen receptor splice variant 7 (AR-V7) in circulating tumour cells (CTCs) has been associated with resistance to abiraterone and enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC). We used a sensitive whole blood RT-PCR assay that does not require CTC enrichment to correlate outcomes on abiraterone with whole blood expression of AR-V7 and other prostate cancer-associated transcripts.
Expression of AR-V7, FOXA1, GRHL2, HOXB13, KLK2, KLK3 and TMPRSS2:ERG mRNA were assessed in 2.5 ml whole blood of 27 mCRPC patients and 33 non-cancer controls (discovery cohort). Cycle threshold (Ct) values of controls with highest gene expression were set as the threshold for a positive test. Thresholds were then applied to a validation cohort of 37 patients with mCRPC commencing abiraterone. Gene expression was correlated with PSA response rate (PSA RR) using Chi squared test; and with time to PSA progression (PSA-PFS) and overall survival (OS) using log-rank.
In the discovery cohort, 3/27 (11.1%) CRPC patients were AR-V7 positive vs. 4/37 (10.8%) of patients in the validation cohort. In the validation cohort, patients with an AR-V7+ test had lower PSA RR (0% vs. 42%, P=0.27) together with shorter median PSA-PFS (0.7 months vs. 4.0 months, P<0.001) and median OS (5.5 months vs. 22.1 months, P<0.001).
RT-PCR detection of AR-V7 transcripts in whole blood was associated with inferior outcomes in patients treated with abiraterone. These results reinforce the potential utility of AR-V7 as a prognostic and predictive biomarker for mCRPC.
The Journal of urology. 2016 Jul 16 [Epub ahead of print]
Tilman Todenhöfer, Arun Azad, Craig Stewart, Jian Gao, Bernhard J Eigl, Martin E Gleave, Anthony M Joshua, Peter C Black, Kim N Chi
Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Department of Urology, University Hospital, Tübingen, Germany., British Columbia Cancer Agency, British Columbia, Vancouver, Canada; Department of Medicine, Monash University, Melbourne, Australia., Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada., Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada., British Columbia Cancer Agency, British Columbia, Vancouver, Canada., Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada., Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada., Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; British Columbia Cancer Agency, British Columbia, Vancouver, Canada. Electronic address: .