The Prognostic Value of Androgen Receptor Splice Variant 7 in Castration-Resistant Prostate Cancer Treated With Novel Hormonal Therapy or Chemotherapy: A Systematic Review and Meta-analysis
Overview
Affiliations
Purpose: This study aimed to evaluate the prognostic role of AR-V7 in terms of prostate-specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS) in CRPC patients treated with novel hormonal therapy (NHT) (Abiraterone and Enzalutamide) or taxane-based chemotherapy (Docetaxel and Cabazitaxel).
Methods: A comprehensive literature search was conducted on PubMed, Embase, and the Web of Science from inception to February 2020. Studies focusing on the prognostic values of AR-V7 in CRPC patients treated with NHT or chemotherapy were included in our meta-analysis. The OS and PFS were analyzed based on Hazard ratios (HRs) and 95% confidence intervals (CIs). Furthermore, Odds ratios (ORs) and 95% CIs were summarized for the AR-V7 conversion after treatment and the PSA response.
Results: The AR-V7 positive proportion increased significantly after NHT treatment (OR 2.56, 95% CI 1.51-4.32, P<0.001), however, it declined after chemotherapy (OR 0.51, 95% CI 0.28-0.93, P=0.003). AR-V7-positive patients showed a significantly decreased PSA response rate after NHT (OR 0.13, 95% CI 0.09-0.19, P<0.001) but not statistically significant for chemotherapy (OR 0.63, 95% CI 0.40-1.01, P=0.06). Notably, PFS (HR 3.56, 95% CI 2.53-5.01, P<0.001) and OS (HR 4.47, 95% CI 3.03-6.59, P<0.001) were worse in AR-V7-positive ttreated with NHT. Similarly, AR-V7 positivity correlated with poor prognosis after chemotherapy as evidenced by shorter OS (HR 1.98, 95% CI 1.48-2.66, P<0.001) and a significantly shorter PFS (HR 1.35, 95% CI 0.97-1.87, P=0.07).
Conclusion: NHT treatment increased AR-V7 positive proportion whereas chemotherapy decreased it. Moreover, AR-V7 positivity correlated with lower PSA response, poorer PFS, and OS in CRPC treated with NHT, and shorter OS in patients receiving chemotherapy.
Inhibition of the serine/threonine kinase BUB1 reverses taxane resistance in prostate cancer.
Martinez M, Lyles R, Peinetti N, Grunfeld A, Burnstein K iScience. 2023; 26(9):107681.
PMID: 37705955 PMC: 10495664. DOI: 10.1016/j.isci.2023.107681.
Gravestock P, Clark E, Morton M, Sharma S, Fisher H, Walker J NIHR Open Res. 2023; 2:49.
PMID: 37035713 PMC: 7614403. DOI: 10.3310/nihropenres.13284.2.
Miller K, Henry I, Maylin Z, Smith C, Arunachalam E, Pandha H Front Oncol. 2023; 13:1129140.
PMID: 36937454 PMC: 10014620. DOI: 10.3389/fonc.2023.1129140.
Overcoming Obstacles in Liquid Biopsy Developments for Prostate Cancer.
Jang A, Rauterkus G, Vaishampayan U, Barata P Onco Targets Ther. 2022; 15:897-912.
PMID: 36051571 PMC: 9427206. DOI: 10.2147/OTT.S285758.
Khan T, Becker T, Scott K, Descallar J, de Souza P, Chua W Front Oncol. 2022; 12:868031.
PMID: 35372002 PMC: 8971301. DOI: 10.3389/fonc.2022.868031.