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

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

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

^*Correspondence: dupeng9000@126.com (Peng Du)
^†These authors contributed equally.

J. Mens. Health 2022, 18(3), 61; https://doi.org/10.31083/j.jomh1803061

Submitted: 20 October 2021 | Accepted: 1 December 2021 | Published: 2 March 2022

This is an open access article under the CC BY 4.0 license.

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 $\geq$ 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 $\pm$ 1.03 vs. 7.29 $\pm$ 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 $\pm$ 0.66 vs. 7.57 $\pm$ 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

Figures

Fig. 1.

Previous article in this issue

Next article in this issue

Fig. 1.

Kaplan–Meier analysis of prostate specific antigen (PSA) progression free survival (PFS), clinical PFS, radiographic PFS and cancer specific survival (CSS) according to androgen receptor splice variant 7 (AR-V7) status in abiraterone (Abi) treated patients. (A) PSA PFS of AR-V7-negative patients was longer than AR-V7-positive patients by log-rank test, p $<$ 0.0001. (B) Clinical PFS of AR-V7-negative patients was longer than AR-V7-positive patients by log-rank test, p = 0.012. (C) Radiographic PFS of AR-V7-negative patients was longer than AR-V7-positive patients by log-rank test, p = 0.037. (D) No differences in CSS were observed according to AR-V7 status by log-rank test, p = 0.474.

1 of 2

J. Mens. Health Print ISSN 1875-6867 Electronic ISSN 1875-6859