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

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.