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. 2022 Mar 18:12:868031.
doi: 10.3389/fonc.2022.868031. eCollection 2022.

Prognostic and Predictive Value of Liquid Biopsy-Derived Androgen Receptor Variant 7 (AR-V7) in Prostate Cancer: A Systematic Review and Meta-Analysis

Tanzila Khan  1   2   3 , Therese M Becker  2   3   4 , Kieran F Scott  1   2 , Joseph Descallar  4   5 , Paul de Souza  1   2   6 , Wei Chua  1   2   4   7 , Yafeng Ma  2   3   4
Affiliations

Prognostic and Predictive Value of Liquid Biopsy-Derived Androgen Receptor Variant 7 (AR-V7) in Prostate Cancer: A Systematic Review and Meta-Analysis

Tanzila Khan et al. Front Oncol. .

Abstract

In advanced prostate cancer, access to recent diagnostic tissue samples is restricted and this affects the analysis of the association of evolving biomarkers such as AR-V7 with metastatic castrate resistance. Liquid biopsies are emerging as alternative analytes. To clarify clinical value of AR-V7 detection from liquid biopsies, here we performed a meta-analysis on the prognostic and predictive value of androgen receptor variant 7 (AR-V7) detected from liquid biopsy for patients with prostate cancer (PC), three databases, the Embase, Medline, and Scopus were searched up to September 2021. A total of 37 studies were included. The effects of liquid biopsy AR-V7 status on overall survival (OS), radiographic progression-free survival (PFS), and prostate-specific antigen (PSA)-PFS were calculated with RevMan 5.3 software. AR-V7 positivity detected in liquid biopsy significantly associates with worse OS, PFS, and PSA-PFS (P <0.00001). A subgroup analysis of patients treated with androgen receptor signaling inhibitors (ARSi such as abiraterone and enzalutamide) showed a significant association of AR-V7 positivity with poorer OS, PFS, and PSA-PFS. A statistically significant association with OS was also found in taxane-treated patients (P = 0.04), but not for PFS (P = 0.21) or PSA-PFS (P = 0.93). For AR-V7 positive patients, taxane treatment has better OS outcomes than ARSi (P = 0.01). Study quality, publication bias and sensitivity analysis were integrated in the assessment. Our data show that liquid biopsy AR-V7 is a clinically useful biomarker that is associated with poor outcomes of ARSi-treated castrate resistant PC (CRPC) patients and thus has the potential to guide patient management and also to stratify patients for clinical trials. More studies on chemotherapy-treated patients are warranted.

Systematic review registration: PROSPERO, CRD42021239353.

Keywords: AR-V7; liquid biopsy; meta-analysis; prognosis; prostate cancer.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of literature search and study selection.
Figure 2
Figure 2
Forest plot of hazard ratios (HRs) for association of liquid biopsy AR-V7 status with overall survival (OS) in all included studies. Pooled HRs were calculated using random effect model. AR-V7, androgen receptor splice variant 7; CI, confidence interval and bars indicate 95% CIs. Subgroup analysis (ARSi, enzalutamide or abiraterone; Enz, enzalutamide; Abi, abiraterone; Chemo, taxane based chemotherapy; Miscellaneous, treatments that do not belong to above treatments or not clearly defined) were assessed.
Figure 3
Figure 3
Forest plot of hazard ratios (HRs) for association of liquid biopsy AR-V7 status with PFS in all studies. Pooled HRs were calculated using random effect model. AR-V7: androgen receptor splice variant 7. CI, confidence interval and bars indicate 95% CIs. Subgroup analysis (ARSi, enzalutamide or abiraterone; Enz, enzalutamide; Abi, abiraterone; Chemo, taxane based chemotherapy; Miscellaneous, treatments that do not belong to above treatments or not clearly defined) were assessed.
Figure 4
Figure 4
Forest plot of hazard ratios (HRs) for association of liquid biopsy AR-V7 status with PSA-PFS in all studies. Pooled HRs were calculated using random effect model. AR-V7, androgen receptor splice variant 7; CI, confidence interval and bars indicate 95% CIs. Subgroup analysis (ARSi, enzalutamide or abiraterone; Enz, enzalutamide; Abi, abiraterone; Chemo, taxane based chemotherapy; Miscellaneous, treatments that do not belong to above treatments or not clearly defined) were assessed.
Figure 5
Figure 5
Forest plots for association of liquid biopsy AR-V7 status with OS in (A) AR-V7 positive (ARSi vs. Chemotherapy) and (B) AR-V7 negative patients (ARSi vs. Chemotherapy). Pooled HRs were calculated using random effect model. AR-V7, androgen receptor splice variant 7; CI, confidence interval and bars indicate 95% CIs.
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