A new report in European Urology shows that expression of androgen receptor variants 7 and 9 (AR-V7 and AR-V9) measured in whole blood is not predictive of treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC).

“AR-Vs are truncated isoforms of the AR that retain constitutive activity and are purported to be associated with resistance to novel hormonal therapies (abiraterone and enzalutamide),” explains Arun Azad, senior author of the study. “However, data from the ARMOR-3 trial called this belief into question; hence, we felt it was critical to assess AR-V7 and AR-V9 expression in patients with mCRPC to determine the predictive utility of these AR variants.”

Expression of AR-V7 or AR-V9 was not associated with a PSA response

The team collected whole-blood samples from 37 patients with mCRPC before these men started abiraterone or enzalutamide treatment and determined AR-V RNA levels using reverse transcription (RT)-PCR assays with primers specific for AR-V7 and AR-V9. Clinical outcome data were collected at a median follow-up time of 7.3 months. Overall, 24% of men were AR-V+ (seven were AR-V7+ and two were AR-V9+). Expression of AR-V7 or AR-V9 was not associated with a PSA response (50% decrease at 3 weeks) or PSA-progression-free survival (PFS). Analysing AR-V7 positivity, 57% of AR-V7+ men and 66% of AR-V7− men had a PSA response (P = 0.6). Analysing both AR-V7 and AR-V9 positivity together, 66% of men who were either AR-V7+ or AR-V9+ and 64% of AR-V7−AR-V9− men had a PSA response (P = 0.9). PSA-PFS was also not different between groups in either analysis (P = 0.4 and P = 0.9, respectively).

“These findings are in contrast to several studies that found that AR-V7 expression was a negative predictive factor for patients treated with abiraterone or enzalutamide,” highlights Azad. “However, they support the findings of the ARMOR-3 trial, which assessed AR-V7 expression in circulating tumour cells.”

The team is planning to expand on these results to assess the utility of AR-V expression in whole blood as a biomarker across the disease and treatment spectrum. “We continue to expand and analyse our current patient cohort and are working on detecting additional AR-Vs,” Azad summarizes. “We will also investigate the significance of AR-V expression in the context of other treatments, such as chemotherapy, and in men with earlier-stage prostate cancer, such as hormone-sensitive disease.”