EURURO Vol. 71 No. 4

E107 692

Letter to the Editor
Reply to Marcus V. Cronauer, Axel S. Merseburger,
and[2_TD$DIFF] M. Raschid Hoda’s Letter to the Editor re:
Christof Bernemann, Thomas J. Schnoeller,
Manuel Luedeke, et al. Expression of AR-V7 in
Circulating 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
We appreciate the comments by Cronauer et al on our
recent study In brief, we had reported that a subset of six
out of 21 AR-V7–positive patients (not N = 25 as stated by
Cronauer et al) responded to abiraterone/enzalutamide
According to current paradigms these responders
are unexpected. Cronauer et al speculate that mRNA-
based assays are the underlying reason for the unexpected
responses, and jump to the conclusion that protein-based
assays may overcome assumed limitations To the
best of our knowledge, studies directly comparing
the predictive performance of mRNA- and protein-based
assays are ongoing and results have not been released
(eg, NCT02269982). In light of the authors’ expertise, we
have to assume that Cronauer et al have access to
preliminary supporting data. Until the field has access
to these data, we abstain from unsubstantiated conclusions
because these may trigger (or reinforce) beliefs rather than
providing scientifically sound conclusions to shape opi-
nions. Thus, we see the letter by Cronauer et al as a
theoretical exercise to bridge cell-biological data with
clinical findings that we find intellectually appealing.
We have no stakes in mRNA testing, and for our patients
we hope that protein testing may improve response
predictions. While we agree that proteins are carriers of
biological function, the molecular biology of AR and AR-V7
proteins is by no means black and white. For example, how
do we account for differences in protein degradation when
recent data indicate that AR-V7 is more stable than full-
length How do we account for specificity issues of the
antibody ? How can we identify clonal circulating tumor-
cell subpopulations at the single cell level — as underscored
by Cronauer et al — when reliable identification requires
separate slides ? How do we incorporate findings for
DuCaP cells in which parental as well as enzalutamide-
resistant clones exhibit comparable sensitivity to abirater-
one, despite being AR-V7–positive How do we integrate
the various resistance-mediating aberrations in prostate
cancer, including protein data, alternative transcripts other
than AR-V7, AR gene mutations, and AR gene copy-number
gains ? Tightly focused experiments will be necessary to
clarify these questions. Nonetheless, these molecular
considerations should not distract us from looking at all
possible causes for the unexpected responses; for example,
there seems to be a relation to line of therapy . To
prevent systematic denial of effective therapeutic options,
we should make rational decisions regarding AR-V7 testing
practice . In other words, limiting the explanation of
our findings to analytical testing issues may be an
oversimplification.
Conflicts of interest: The authors have nothing to disclose.
References
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[7] Hoefer J, Akbor M, Handle F, et al. Critical role of androgen receptor
level in prostate cancer cell resistance to new generation antiandro-
gen enzalutamide. Oncotarget.
ava ilable at
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DOIs of original articles: , .
0302-2838/# 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.