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Original Research

Open Access

The association of AR-V7 with resistance to Abiraterone in metastatic castration-resistant prostate cancer

  • Shuo Wang1,†
  • Yudong Cao1,†
  • Xingxing Tang2
  • Xiao Yang1
  • Jinchao Ma1
  • Ziyi Yu1
  • Yong Yang1
  • Peng Du1,*,

1Department of Urology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of education/Beijing), Peking University Cancer Hospital and Institute, 100142 Beijing, China

2Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, 100034 Beijing, China

DOI: 10.31083/j.jomh1803061 Vol.18,Issue 3,March 2022 pp.1-8

Submitted: 20 October 2021 Accepted: 01 December 2021

Published: 31 March 2022

*Corresponding Author(s): Peng Du E-mail: dupeng9000@126.com

† These authors contributed equally.

Abstract

Background: This paper sought to investigate the association between androgen receptor splice variant 7 (AR-V7) status in circulating tumors cells (CTCs) and resistance to abiraterone (Abi) and docetaxel (Doc) in men with metastatic castration-resistant prostate cancer (mCRPC). Methods: This was a prospective clinical study, newly confirmed mCRPC patients who were randomized going to receive Abi or Doc with age ≥18 years were enrolled to detect the AR-V7 mRNA in CTCs. The association of AR-V7 status with Gleason Score, prostate specific antigen response rate (PSA RR), hormone-sensitive duration time (HSDT), time-to event outcomes, including PSA progression-free survival (PFS), clinical PFS, radiographic PFS and cancer-specific survival (CSS) was examined. Results: 139 patients with mCPRC were enrolled; 67 received Abi and 72 received Doc. The proportion of AR-V7-positive patients was 35.8% in Abi-treated patients and 34.7% in Doc-treated patients. Our results were as follows: (1) among men receiving Abi, AR-V7-positive patients had a higher Gleason Score (8.34 ± 1.03 vs. 7.29 ± 0.76, p = 0.012) and lower PSA RR (20.8% vs. 65.1%, p = 0.001) compared with AR-V7-negative patients; in a multivariable COX model, AR-V7 positivity was an independent risk factor for shorter PSA PFS (p = 0.012), clinical PFS (p = 0.036) and radiographic PFS (p = 0.028); (2) among men receiving Doc, AR-V7-positive patients also had a higher Gleason Score compared with AR-V7-negative patients (8.86 ± 0.66 vs. 7.57 ± 0.94, p < 0.0001), but no differences in PSA RR, PSA PFS, clinical PFS, radiographic PFS or CSS were observed; (3) among AR-V7-positive patients, men receiving Abi had lower a PSA RR compared with men receiving Doc (20.8% vs. 48%, p = 0.046); in a multivariable COX model, Abi was an independent risk factor for shorter PSA PFS (p = 0.040) and clinical PFS (p = 0.046); (4) among AR-V7-negative patients, there were no differences in PSA RR, PSA PFS, clinical PFS, radiographic PFS or CSS between Abi- and Doc-treated patients. Conclusion: AR-V7-positive patients commonly have a higher Gleason Score than AR-V7 negative patients, and AR-V7 positivity is strongly associated with Abi resistance in mCRPC but is not associated with the effectiveness of Doc.

Keywords

Castration-resistant prostate cancer; Androgen receptor splice variant 7; Abiraterone; Docetaxel

Cite and Share

Shuo Wang,Yudong Cao,Xingxing Tang,Xiao Yang,Jinchao Ma,Ziyi Yu,Yong Yang,Peng Du. The association of AR-V7 with resistance to Abiraterone in metastatic castration-resistant prostate cancer. Journal of Men's Health. 2022. 18(3);1-8.

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