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Clinical Utility of CLIA-Grade AR-V7 Testing in Patients With Metastatic Castration-Resistant Prostate Cancer.


ABSTRACT: A splice variant of the androgen receptor, AR-V7, confers resistance to AR-targeted therapies (ATTs) but not taxane chemotherapies in patients with metastatic castration-resistant prostate cancer. Since August 2015, a clinical-grade assay to detect AR-V7 messenger RNA expression in circulating tumors cells (CTCs) has been available to providers through a Clinical Laboratory Improvement Amendments-certified laboratory at Johns Hopkins University.We contacted ordering providers of the first 150 consecutive tests by using a questionnaire-based survey to determine how the results of AR-V7 testing were used to influence clinical practice.In all, 142 (95%) of 150 questionnaires were completed by 38 providers from 29 sites across the United States and Canada. AR-V7 test results were reported either as CTC- (28%), CTC+/AR-V7- (30%), or CTC+/AR-V7+ (42%). Prevalence of AR-V7 detection increased with prior exposure to ATTs (abiraterone and enzalutamide naïve, 22%; after abiraterone or enzalutamide, 35%; after abiraterone and enzalutamide, 43%). Overall, management was affected by AR-V7 testing in 53% of the patients and even more often with CTC+/AR-V7+ results. AR-V7+ patients were commonly switched from ATT to taxane chemotherapy (43%) or were offered a clinical trial (43%); management remained unchanged in only 14% of these patients. Overall, patients who had a change in management on the basis of AR-V7 testing were significantly more likely to achieve a physician-reported 50% decline in prostate-specific antigen response on next-line therapy than those who did not change treatment (54% v 31%; P = .015).Providers used AR-V7 testing to influence clinical decision making more often than not. Physicians reported thatmenwithAR-V7+results had the most treatment changes, and such men were preferentially managed with taxane therapy or offered a clinical trial, which may have improved outcomes.

SUBMITTER: Markowski MC 

PROVIDER: S-EPMC5697780 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Clinical Utility of CLIA-Grade AR-V7 Testing in Patients With Metastatic Castration-Resistant Prostate Cancer.

Markowski Mark C MC   Silberstein John L JL   Eshleman James R JR   Eisenberger Mario A MA   Luo Jun J   Antonarakis Emmanuel S ES  

JCO precision oncology 20171030


<h4>Purpose</h4>A splice variant of the androgen receptor, AR-V7, confers resistance to AR-targeted therapies (ATTs) but not taxane chemotherapies in patients with metastatic castration-resistant prostate cancer. Since August 2015, a clinical-grade assay to detect AR-V7 messenger RNA expression in circulating tumors cells (CTCs) has been available to providers through a Clinical Laboratory Improvement Amendments-certified laboratory at Johns Hopkins University.<h4>Methods</h4>We contacted orderi  ...[more]

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