Clinical utility of the nuclear-localized AR-V7 biomarker in circulating tumor cells in improving physician treatment choice in castration-resistant prostate cancer Journal Article

  

Authors:	Graf, R. P.; Hullings, M.; Barnett, E. S.; Carbone, E.; Dittamore, R.; Scher, H. I.
Article Title:	Clinical utility of the nuclear-localized AR-V7 biomarker in circulating tumor cells in improving physician treatment choice in castration-resistant prostate cancer
Abstract:	Background: Proof of the clinical utility of a biomarker is when its use informs a management decision and improves patient outcomes relative to when it is not used. Objective: To model the clinical benefit of the nuclear-localized androgen receptor splice variant 7 (AR-V7) test for men with progressing metastatic castration-resistant prostate cancer (mCRPC) at the second line of therapy or greater to inform the choice of an androgen receptor signaling inhibitor (ARSI) or a taxane. Design, setting, and participants: The study population was a cross-sectional cohort of 193 unique patients with progressing mCRPC from whom 255 samples were drawn at the time of the second line or later treatment decision who then received an ARSI or taxane, with up to 3 yr of additional follow-up Circulating tumor cells (CTCs) were identified from blood samples and tested for AR-V7. Physicians were blinded to AR-V7 status and the testing laboratory was blinded to outcomes. Outcome measurements and statistical analyses: We measured physician propensity for choosing an ARSI or taxane based on patient prognosis. We also measured overall survival (OS) adjusted for physician propensity by drug class; OS data were analyzed both without and with knowledge of nuclear-localized AR-V7 status. Results and limitations: Treating physicians had a propensity for choosing a taxane over an ARSI for patients with more advanced disease or who received an ARSI as the immediate prior therapy. After adjusting for physician propensity, discernible OS differences were not observed between taxane- and ARSI-treated patients (median 15.6 vs 14.4 mo; p =0.11). Patients with detectable nuclear-localized AR-V7 in CTCs had superior survival with taxanes over ARSIs (median 9.8 vs 5.7 mo; p = 0.041). AR-V7–negative patients had superior survival on ARSIs over taxanes (p = 0.033) but overlapping curves limit the interpretation. Mutivariable models showed a robust interaction between AR-V7 status and drug, and a lower risk of death on taxanes for AR-V7–positive men. Conclusions: Use of the nuclear-localized AR-V7 CTC test to inform treatment choice can improve patient outcomes relative to decisions based solely on standard-of-care measures. Patient summary: Men with metastatic prostate cancer who test positive for AR-V7 protein in circulating tumor cells are likely to live longer if taxane chemotherapy is used. © 2019 Use of the nuclear-localized AR-V7 biomarker in circulating tumor cells can improve physician treatment choices aimed at extending life in castration-resistant prostate cancer. © 2019
Keywords:	adult; cancer chemotherapy; controlled study; treatment outcome; aged; unclassified drug; human cell; major clinical study; overall survival; cancer growth; bone metastasis; paclitaxel; outcome assessment; follow up; lymph node metastasis; medical decision making; prostate specific antigen; metastasis; cohort analysis; hemoglobin; docetaxel; prostate cancer; alkaline phosphatase; liver metastasis; lung metastasis; albumin; blood sampling; cellular distribution; androgen receptor; cross-sectional study; lactate dehydrogenase; cell nucleus; circulating tumor cells; circulating tumor cell; castration resistant prostate cancer; drug choice; abiraterone; cabazitaxel; treatment decisions; cancer prognosis; enzalutamide; human; male; priority journal; article; patient risk; apalutamide; liquid biopsy; mortality risk; ar-v7; androgen receptor splice variant 7
Journal Title:	European Urology
Volume:	77
Issue:	2
ISSN:	0302-2838
Publisher:	Elsevier Science, Inc.
Date Published:	2020-02-01
Start Page:	170
End Page:	177
Language:	English
DOI:	10.1016/j.eururo.2019.08.020
PUBMED:	31648903
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85073143345&doi=10.1016%2fj.eururo.2019.08.020&partnerID=40&md5=d0acbd18d051a20dd139b0e05e5afe27
Notes:	Article -- Export Date: 3 February 2020 -- Source: Scopus