Prognostic Value of Androgen Receptor Splice Variant 7 in the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

Abstract

BackgroundThe prognostic value of androgen receptor splice variant 7 (AR-V7) for the treatment response of metastatic castration-resistant prostate cancer (mCRPC) remains unclear. In this study, we aimed to synthesize relevant studies that assessed the prognostic value of AR-V7 status for the treatment response of mCRPC patients treated with androgen receptor signalling inhibitors (ARSis) and chemotherapy.MethodsWe searched the PubMed, Embase, and MEDLINE databases by using the keywords AR-V7 and prostate cancer to identify relevant studies published before 25 September 2019. The main outcomes were prostate-specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS). Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale.ResultsA total of 1,545 patients from 21 studies were included. For the mCRPC patients treated with ARSis, AR-V7-positive patients had a lower PSA response rate (OR 6.01, 95% CI 2.88–12.51; P < 0.001), shorter PFS (HR 2.56, 95% CI 1.80–3.64; P < 0.001) and shorter OS (HR 4.28, 95% CI 2.92–6.27; P < 0.001) than AR-V7-negative patients. Although AR-V7-positive patients treated with chemotherapy also had a lower PSA response rate (OR 2.23, 95% CI 1.38–3.62; P = 0.001) and shorter OS than AR-V7-negative patients (HR 1.60, 95% CI 1.02–2.53; P = 0.043), there was no significant difference in PFS (HR 1.05, 95% CI 0.74–1.49; P = 0.796) between these groups. Furthermore, AR-V7-positive patients receiving ARSis had a shorter median OS than those receiving chemotherapy (HR 3.50, 95% CI 1.98–6.20; P < 0.001); There was no significant difference among AR-V7-negative patients (HR 1.30, 95% CI 0.64–2.62; P = 0.47).ConclusionsAR-V7 is a potential biomarker of treatment resistance in mCRPC patients. AR-V7-positive mCRPC patients had poorer treatment outcomes than AR-V7-nagetive patients when treated with ARSis. AR-V7-positive patients have better outcomes when treated with taxane than ARSis. Furthermore, the ability of AR-V7 status to predict treatment outcomes varies from different detection methods. The detection of AR-V7 before treatment is important for the selection of treatment modalities for mCRPC patients.

Enzalutamide-Resistant Progression of Castration-Resistant Prostate Cancer Is Driven via the JAK2/STAT1-Dependent Pathway

“…This suggested that ARv7 might be involved in the cross-resistance between ENZ and ABI. Although ARv7-positive patients showed much worse treatment responses to NHT (Armstrong et al, 2020;Wang et al, 2020a;Wang et al, 2020b), the clinical data analysis demonstrated that these patients could significantly benefit from taxane chemotherapy, which was possibly related to the higher activity of the E2F1/AR3 feed-forward loop (Xu et al, 2020). The CXCR7-JAK2/STAT1 signaling pathway, as an independent AR bypass pathway, may also participate in resistance to androgen target therapy.…”

Liquid Biopsy in Prostate Cancer Management—Current Challenges and Future Perspectives

“…It has been demonstrated that the exosome-RNA and CTC isolated by plasma samples could be used to detect the androgen receptor splicing variant 7 (AR-V7), a predictive variant of resistance to AR signaling inhibitors. Furthermore, Tagawa and coworkers showed that the absence of the same variants in mCRPC CTC patients may be associated with better taxane treatment outcomes [111][112][113]. In addition, liquid biopsy could be also used to predict resistance to PARP inhibitors (PARPi), which are approved for treatment or maintenance therapy for several malignancies, including PCa.…”

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.…”