EURURO Vol. 73 No. 1

E9 148

Letter to the Editor
Re: Marzia Del Re, Elisa Biasco, Stefania Crucitta, et al.
The Detection of Androgen Receptor Splice Variant
7 in Plasma-derived Exosomal RNA Strongly Predicts
Resistance to Hormonal Therapy in Metastatic Prostate
Cancer Patients. Eur Urol 2017;71:680–7
We read with great interest the paper by Del Re et al
regarding detection of androgen receptor splice variant 7
(AR-V7) in plasma-derived exosomal RNA frompatients with
metastatic castration-resistant prostate cancer (mCRPC)
treated with novel AR-directed therapies (ADT), such as
abiraterone and enzalutamide, considered as a strong
predictor of clinical outcome for this patient cohort. The
authors reported on 14 patients who were AR-V7–positive
(AR-V7+) and 22 who were AR-V7 –negative (AR-V7 ) with
median progression-free survival (PFS) of 3 and 20 mo
(p < 0.001) and median overall survival (OS) of 8 mo and not
reached (p < 0.001), respectively.
However, 13 of the 14 AR-V7+ patients (93%) received
treatment in the post-docetaxel setting, including six
patients (43%) with visceral metastases and four men
(29%) pretreated with abiraterone and four (29%) with
cabazitaxel, whereas 11 of 22 AR-V7 patients (50%) had
post-docetaxel mCRPC, and only one case with visceral
metastases and no cases treated with another ADT or
cabazitaxel. The differences in median PFS and OS could be
affected by these different prognostic factors in the AR-V7+
and AR-V7 groups. Previous studies reported worse PFS and
OS with ADT among pretreated patients A recent study
reported on the association between plasma AR status and
outcome among post-docetaxel mCRPC patients treated
with ADT , but we excluded 48 cases pretreated with
other ADTs to avoid a significantly negative impact on PFS
and OS: median PFS was 6.2 mo in ADT-naïve and 3.6 mo in
ADT-pretreated men (hazard ratio [HR] 2.14, 95% confidence
interval [CI] 1.43–3.20; p = 0.0002) while median OS was
14.3 versus 8.3 mo (HR 1.76, 95% CI 1.16–2.64; p = 0.007).
In their multivariate analysis including AR-V7 status and
expression levels, prior taxane use, and hemoglobin levels,
AR-V7 status was not an independent factor, probably as a
consequence of the impact of prior docetaxel use . More-
over, the multivariate analysis should be adjusted for the
different distribution of patient characteristics between the
AR-V7 groups reported in Table 1 prior use of docetaxel
(Fisher’s exact test, p = 0.011), prior use of abiraterone
(p = 0.017), and the presence of visceral metastases
(p = 0.008).
The authors compared their results to those from the
pivotal study on AR-V7 detected in circulating tumor cells
(CTCs) in post-docetaxel mCRPC , and observed similar
results for AR-V7+ status, with the larger difference in
median PFS compared to AR-V7 patients suggesting higher
sensitivity for the exosome approach over CTCs, but the
magnitude of the reported difference in PFS compared to
AR-V7 could be a consequence of the proportion of pre-
docetaxel cases (50%) besides the fewer pretreated post-
docetaxel cases in the AR-V7 group. The authors should
contextualize their results within the post-docetaxel
mCRPC setting to yield a more homogeneous result for
the effect of AR-V7 detection.
In conclusion, the authors are the first to describe a
plasma-derived approach using exosomes for AR-V7 detec-
tion that may have several cost and feasibility advantages
over CTCs, but a direct comparison of AR-V7 detection
between exosomes and CTCs in larger studies with
homogeneous patient populations could provide the evi-
dence needed to consider this tool as a potential source of a
circulating biomarker in mCRPC.
Conflicts of interest: The authors have nothing to disclose.
References
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DOI of original article: .
0302-2838/© 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.