Improved Androgen Receptor Splice Variant 7 Detection Using a Highly Sensitive Assay to Predict Resistance to Abiraterone or Enzalutamide in Metastatic Prostate Cancer Patients.
Androgen receptor signaling inhibitors
Androgen receptor splice variant 7 (AR-V7)
Circulating tumor cells
Highly sensitive AR-V7 assay
Liquid profiling
Metastatic castration-resistant prostate cancer
Journal
European urology oncology
ISSN: 2588-9311
Titre abrégé: Eur Urol Oncol
Pays: Netherlands
ID NLM: 101724904
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
02
05
2019
revised:
04
07
2019
accepted:
15
08
2019
pubmed:
5
11
2019
medline:
2
2
2022
entrez:
3
11
2019
Statut:
ppublish
Résumé
In metastatic castration-resistant prostate cancer (mCRPC), androgen receptor splice variant 7 (AR-V7) expression is associated with a low response to androgen receptor signaling (ARS) inhibitors such as abiraterone or enzalutamide. To perform a highly sensitive assay for detecting AR-V7 (hsAR-V7) in circulating tumor cells (CTCs) and evaluate its ability to predict response to ARS inhibitors. From 41 mCRPC patients, CTCs were prospectively enriched using AdnaTest platform and analyzed for AR-V7 with and without the highly sensitive assay. The first objective of the study was to compare AR-V7 detection rates with and without the highly sensitive assay. Next, we investigated how AR-V7 (detected without the highly sensitive assay) and hsAR-V7 status influenced prostate-specific antigen (PSA) response and long-term clinical outcomes (PSA progression-free survival [PFS] and radiological PFS) after ARS-inhibitor treatment. Finally, discriminatory abilities of the assays were assessed by C-index to compare their impact on long-term clinical outcomes. AR-V7 detection rates increased from 22% to 56% when the highly sensitive assay was used. The discriminatory abilities of hsAR-V7 for PSA PFS (C-index, 0.74; 95% confidence interval [CI], 0.60-0.88) and radiological PFS (0.70; 95% CI, 0.55-0.85) were higher than those of AR-V7 detected without the highly sensitive assay (0.60, 0.51-0.72, and 0.56, 0.44-0.67, respectively). After ARS-inhibitor treatment, PSA response was lower in hsAR-V7 The hsAR-V7 assay achieved the highest AR-V7 detection rates among those reported in mCRPC. Discriminatory abilities for long-term clinical outcomes were better with hsAR-V7 assay. We prospectively analyzed circulating tumor cells from men with metastatic castration-resistant prostate cancer for androgen receptor splice variant 7 (AR-V7) status using a highly sensitive assay. It yielded higher AR-V7 detection rates and predicted resistance to androgen receptor signaling inhibitors with better discriminatory abilities for long-term clinical outcomes.
Sections du résumé
BACKGROUND
In metastatic castration-resistant prostate cancer (mCRPC), androgen receptor splice variant 7 (AR-V7) expression is associated with a low response to androgen receptor signaling (ARS) inhibitors such as abiraterone or enzalutamide.
OBJECTIVE
To perform a highly sensitive assay for detecting AR-V7 (hsAR-V7) in circulating tumor cells (CTCs) and evaluate its ability to predict response to ARS inhibitors.
DESIGN, SETTING, AND PARTICIPANTS
From 41 mCRPC patients, CTCs were prospectively enriched using AdnaTest platform and analyzed for AR-V7 with and without the highly sensitive assay.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
The first objective of the study was to compare AR-V7 detection rates with and without the highly sensitive assay. Next, we investigated how AR-V7 (detected without the highly sensitive assay) and hsAR-V7 status influenced prostate-specific antigen (PSA) response and long-term clinical outcomes (PSA progression-free survival [PFS] and radiological PFS) after ARS-inhibitor treatment. Finally, discriminatory abilities of the assays were assessed by C-index to compare their impact on long-term clinical outcomes.
RESULTS AND LIMITATIONS
AR-V7 detection rates increased from 22% to 56% when the highly sensitive assay was used. The discriminatory abilities of hsAR-V7 for PSA PFS (C-index, 0.74; 95% confidence interval [CI], 0.60-0.88) and radiological PFS (0.70; 95% CI, 0.55-0.85) were higher than those of AR-V7 detected without the highly sensitive assay (0.60, 0.51-0.72, and 0.56, 0.44-0.67, respectively). After ARS-inhibitor treatment, PSA response was lower in hsAR-V7
CONCLUSIONS
The hsAR-V7 assay achieved the highest AR-V7 detection rates among those reported in mCRPC. Discriminatory abilities for long-term clinical outcomes were better with hsAR-V7 assay.
PATIENT SUMMARY
We prospectively analyzed circulating tumor cells from men with metastatic castration-resistant prostate cancer for androgen receptor splice variant 7 (AR-V7) status using a highly sensitive assay. It yielded higher AR-V7 detection rates and predicted resistance to androgen receptor signaling inhibitors with better discriminatory abilities for long-term clinical outcomes.
Identifiants
pubmed: 31676281
pii: S2588-9311(19)30136-1
doi: 10.1016/j.euo.2019.08.010
pii:
doi:
Substances chimiques
Androstenes
0
Benzamides
0
Nitriles
0
Receptors, Androgen
0
Phenylthiohydantoin
2010-15-3
enzalutamide
93T0T9GKNU
abiraterone
G819A456D0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
609-617Informations de copyright
Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.