The Role of Androgen Receptor Splicing Variant 7 in Predicting the Prognosis of Metastatic Castration-Resistant Prostate Cancer: Systematic Review and Meta-Analysis

Objective: The purpose of this meta-analysis was to study the prognostic effects of androgen receptor splicing variant 7 (AR-V7) on metastatic castration-resistant prostate cancer (mCRPC) under different treatment options (chemotherapy, hormone therapy). Methods: We conducted a systematic search of PubMed, EMBASE and Cochrane databases for clinical studies up to June 4, 2021, and used prostate-specific antigen (PSA) progression free-survival (PSA-PFS), radiologic PFS (r-PFS), overall survival (OS) and PSA response rate (PSA RR) as the main endpoints. Subgroup analyses were conducted based on the source of the specimens. STATA v.15 software was used for data analysis. Results: Twenty-one studies were included in this meta-analysis, with a total of 1578 samples. In the abiraterone (AA)/enzalutamide (E) treatment group, AR-V7 positive patients had worse PSA-PFS (hazard ratio [HR] = 3.40; 95% confidence interval [95%CI] 2.56-4.51; P < 0.05) and worse r-PFS (HR = 2.69; 95%CI 1.70-4.24; P < 0.05) and OS (HR = 3.02; 95%CI 1.73-5.30; P < 0.05). Multivariate Cox regression results showed that AR-V7 positive status was an independent risk factor for OS in the AA/E treatment group. In the taxane treatment group, AR-V7-positive and negative patients had similar PSA-PFS (HR = 0.87; 95%CI 0.46-1.63; P = 0.657), r-PFS (HR = 1.01; 95%CI 0.53-1.96; P = 0.965) and OS (HR = 1.50; 95%CI 0.89-2.52; P = 0.127). For AR-V7-positive patients, the difference in OS between taxane and AA/E treatment was not statistically significant (HR = 1.03; 95%CI 0.52-2.06; P = 0.930). However, multivariate Cox regression results suggested that for AR-V7-positive patients, taxane therapy was a protective factor for OS (HR = 0.35; 95%CI 0.20-0.60; P < 0.05). Conclusion: The expression of AR-V7 indicates a poor prognosis and is an independent risk factor for OS in AA/E-treated mCRPC patients. However, AR-V7 positive status does not play the same role in taxane-treated patients. In addition, compared to AA/E, taxane treatment is a protective factor for OS in AR-V7-positive patients. AR-V7 may thus be an effective biomarker for treatment prognosis in patients with mCRPC.

Automated summary

AR-V7 expression indicates poor prognosis and is an independent risk factor for OS in AA/E-treated mCRPC patients, but plays a different role in taxane-treated patients. Taxane treatment is a protective factor for OS in AR-V7-positive patients compared to AA/E. AR-V7 may be an effective biomarker for treatment prognosis in mCRPC patients.