LAUSR

A critical unmet need in advanced prostate cancer (PCa) management is how to best sequence the available lifeprolonging therapies to maximize clinical benefit for the individual patient and, in particular, to identify those men most likely to respond to a next-generation hormonal agent (abiraterone or enzalutamide) versus a taxane agent (docetaxel or cabazitaxel). In 2014, it was first reported that the detection of androgen receptor splice variant 7 (AR-V7) messenger RNA (mRNA) in circulating tumor cells (CTCs) isolated from the blood of patients about to start a new line of therapy for castration-resistant prostate cancer (CRPC) was associated with a lack of response to abiraterone and enzalutamide [1]. This clinical observation was consistent with the known biological functions of AR-V7 and the mechanism of action of the drugs, and it was subsequently confirmed by multiple groups using a range of laboratory assays [2]. No such association was observed with taxane-based therapies, suggesting that this class of agent would be more likely to benefit patients in whom AR-V7 was detected in CTCs [3,4]. The report by Bernemann et al [5] in this month’s issue of European Urology, in which the authors conclude that ‘‘6 of 21 AR-V7–positive patients experienced benefit’’ from abiraterone or enzalutamide, appears to contradict the growing body of evidence. A critical review of the findings, however, does not support this conclusion and highlights the need for adherence to the evidentiary standards for biomarker validation (analytical and clinical) and the reporting of treatment outcomes. It also underlines the appropriate concern of regulators and