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

Abstract

PurposeThis 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).MethodsA 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.ResultsThe 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).ConclusionNHT 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.

Impact of Time to Castration Resistance on Survival in Metastatic Hormone Sensitive Prostate Cancer Patients in the Era of Combination Therapies

“…However, OS differences between TTCR groups cannot be explained by differences in patient or baseline tumor characteristics alone. It is very likely that other factors, such as genetic differences or gene mutations, play a crucial role in TTCR for which we could unfortunately not account for (27,28).…”

Commentary: Meta-Analyses Reporting the Prognostic Value of Androgen Receptor Splice Variant 7 in Castration-Resistant Prostate Cancer

“…The concurrent systematic reviews recently published in Frontiers in Oncology by Zhize Wang et al (1) and Jiaxin Wang et al (2) provide a very similar report on the prognostic value of the androgen receptor splice variant 7 (AR-V7) in castration-resistant prostate cancer. As these might appear, at first glance, to be nearly identical, we believed it was pertinent to herein highlight the differences and summarize the findings.…”

Beyond the Androgen Receptor: The Sequence, the Mutants, and New Avengers in the Treatment of Castrate-Resistant Metastatic Prostate Cancer

“…1 In recent years, the molecular characterization of mCRPC has proved critical to improving disease outcome and understanding responses to antiandrogen therapy, chemotherapy, targeted therapies, and immunotherapy. [2][3][4][5][6][7][8][9][10][11][12] Identification of novel therapeutics to improve survival and achieve durable responses in CRPC is a clinical necessity. In this review, we discuss the sequencing of the available avengers, the mutant avengers (i.e., targeting androgen-indifferent prostate cancers [AIPC]), and the evolving new avengers for the treatment of mCRPC.…”