Literature DB >> 29508425

AR-V7 in circulating tumor cells cluster as a predictive biomarker of abiraterone acetate and enzalutamide treatment in castration-resistant prostate cancer patients.

Takatsugu Okegawa1, Naoki Ninomiya1, Kazuki Masuda1, Yu Nakamura1, Mitsuhiro Tambo1, Kikuo Nutahara1.   

Abstract

OBJECTIVE: We examined whether androgen receptor splice variant 7 (AR-V7) in circulating tumor cell(CTC)clusters can be used to predict survival in patients with bone metastatic castration resistant-prostate cancer (mCRPC) treated with abiraterone or enzalutamide.
METHODS: We retrospectively enrolled 98 patients with CRPC on abiraterone or enzalutamide, and investigated the prognostic value of CTC cluster detection (+ v -) and AR-V7 detection (+ v -) using a CTC cluster detection - based AR-V7 mRNA assay. We examined ≤50% prostate-specific antigen (PSA) responses, PSA progression-free survival (PSA-PFS), clinical and radiological progression-free survival (radiologic PSF), and overall survival (OS). We then assessed whether AR-V7 expression in CTC clusters identified after On-chip multi-imaging flow cytometry was related to disease progression and survival after first-line systemic therapy.
RESULTS: All abiraterone-treated or enzalutamide-treated patients received prior docetaxel. The median follow-up was 20.7 (range: 3.0-37.0) months in the abiraterone and enzalutamide cohorts, respectively. Forty-nine of the 98 men (50.0%) were CTC cluster (-), 23 of the 98 men (23.5%) were CTC cluster(+)/AR-V7(-), and 26 of the 98 men (26.5%) were CTC cluster(+)/AR-V7(+). CTC cluster(+)/AR-V7(+) patients were more likely to have EOD ≥3 at diagnosis (P = 0.003), pain (P = 0.023), higher alkaline phosphatase levels (P < 0.001), and visceral metastases (P < 0.001). On multivariable analysis, pretherapy CTC cluster(+), CTC cluster(+)/AR-V7(-), and ALP >UNL were independently associated with a poor PSA-PFS, radiographic PFS, and OS in abiraterone-treated patients and enzalutamide-treated patients.
CONCLUSION: The CTC clusters and AR-V7-positive CTC clusters detected were important for assessing the response to abiraterone or enzalutamide therapy and for predicting disease outcome.
© 2018 Wiley Periodicals, Inc.

Entities:  

Keywords:  androgen receptor splice variant 7; biomarker; castration-resistant prostate cancer; circulating tumor cells cluster

Mesh:

Substances:

Year:  2018        PMID: 29508425     DOI: 10.1002/pros.23501

Source DB:  PubMed          Journal:  Prostate        ISSN: 0270-4137            Impact factor:   4.104


  20 in total

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