EURURO Vol. 71 No. 4

E105 692

Letter to the Editor
Re: Christof Bernemann, Thomas J. Schnoeller, Manuel
Luedeke, et al. Expression of AR-V7 in Circulating
[3_TD$DIFF]Tumour Cells Does Not Preclude Response to Next
Generation Androgen Deprivation Therapy in Patients
with Castration Resistant Prostate Cancer. Eur Urol
2017;71:1–3
Failure of endocrine treatment in prostate cancer (PCa) is
often associated with the emergence of constitutively
active, androgen receptor (AR)-splice variants (AR-V).
Devoid of a ligand-binding domain, AR-Vs are insensitive
to all classical endocrine therapies targeting directly
(antiandrogens) or indirectly (castration) the androgen/
AR-signaling axis . Recent clinical reports suggest that
the presence of AR-V7 transcripts in liquid biopsies of PCa
patients (circulating tumor cells [CTCs] or cell free serum
messenger RNA [mRNA]) is a strong predictor of abirater-
one/enzalutamide insensitivity . In contrast, Berne-
mann and colleagues recently showed in a preliminary
study that 25% of patients (six out of 25) presenting with
AR-V7 positive CTCs, were still responsive to abiraterone or
enzalutamide. The authors suggest that AR-V7 in the CTCs
of castration-resistant PCa (CRPC) patients does not
preclude a response to next generation androgen depriva-
tion. In consequence, abiraterone or enzalutamide should
not be systematically denied to patients with an AR-V7
positive CTC status, especially since alternative treatment
options are limited.
The fact that AR-V7-mRNA is not a perfect predictor of
enzalutamide/abiraterone failure is an important finding,
although not unexpected. Taking advantage of their unique
exon compositions and/or exon-exon junctions, different
AR-Vs can be reliably detected by reverse transcription
polymerase chain reaction Due to its specificity and
high sensitivity, the detection of AR-V7 mRNA by reverse
transcription polymerase chain reaction is the current
method of choice, especially when tumor material (eg,
CTCs) is sparse Unfortunately, the detection of AR-V7
mRNA from pooled CTCs has its limitations as AR-V7
transcripts do not preclude the presence of AR-V7 protein
nor do they give any information on CTC clonal subpopula-
tions or AR-V7 nuclear localization, the latter being a
prerequisite for the genomic functions of a constitutively
active AR-variant . To overcome the limitations
of mRNA-based AR-V7 assays Scher et al recently
evaluated a commercial platform/assay
) able to analyze the presence, clonal selection, and
intracellular localization of AR-V7 in CTCs of patients
suffering from advanced PCa. As the AR-V7 protein has
been implicated in the development of CRPC and the
resistance to abiraterone and enzalutamide, the addition-
al information delivered by protein-based AR-V7 assays,
as described by Scher et al , should reinforce our
knowledge about the role of AR-V7 as an effector/marker
in CRPC.
Conflicts of interest: The authors have nothing to disclose.
References
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DOI of original article: .
0302-2838/# 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.