A new study in European Urology shows that knowledge of the androgen receptor variant 7 protein (AR-V7) status of circulating tumour cells (CTCs) when making therapy decisions at the point of starting the second or greater line of therapy would prolong survival in men with progressing metastatic castration-resistant prostate cancer (mCRPC).

Men with mCRPC usually initially receive a next-generation AR signalling inhibitor (ARSI), but the best treatment after ARSI failure (taxane-based chemotherapy or a further ARSI) remains unclear. Two previous cohort analyses showed that men who had nuclear-localized AR-V7 in CTCs before starting second-line therapy had more favourable overall survival when receiving a taxane than when receiving an ARSI. In this new study, Graf et al. used those data with an extended follow-up period to investigate drivers of treatment choice when AR-V7 status is unknown and to estimate survival had the status been available to show clinical utility of an AR-V7 biomarker test. The analysis showed that the most influential drivers for physicians choosing a taxane were the number of previous systemic mCRPC therapies, liver metastases, PSA level and ARSI as the preceding treatment. Men who were assigned a taxane had more aggressive disease, more previous therapies and a higher risk of death than those assigned an ARSI.

Men assigned an ARSI had longer overall survival than those assigned a taxane (median 17.4 and 13.0 months; P = 0.00021), but when adjusting for physician choice propensity no difference was seen. Notably, taking into account AR-V7 status, AR-V7+ men had longer survival when receiving a taxane than when receiving an ARSI (median 9.8 and 5.7 months; P = 0.041), and AR-V7– men had, overall, longer survival when receiving an ARSI than when receiving a taxane (P = 0.033). Taken together, the analysis shows that survival would have been longer if data on nuclear AR-V7 status of CTCs had been available to guide treatment choice.