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AR-V7 in Peripheral Whole Blood of Patients with Castration-resistant Prostate Cancer: Association with Treatment-specific Outcome Under Abiraterone and Enzalutamide
European Urology ( IF 23.4 ) Pub Date : 2017-08-14 , DOI: 10.1016/j.eururo.2017.07.024
Anna Katharina Seitz 1 , Silvia Thoene 2 , Andreas Bietenbeck 3 , Roman Nawroth 1 , Robert Tauber 1 , Mark Thalgott 1 , Sebastian Schmid 1 , Ramona Secci 2 , Margitta Retz 1 , Jürgen E Gschwend 1 , Jürgen Ruland 2 , Christof Winter 2 , Matthias M Heck 1
Affiliation  

Background

It has been demonstrated that androgen receptor splice variant 7 (AR-V7) expression in circulating tumor cells (CTCs) predicts poor treatment response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide.

Objective

To develop a practical and robust liquid profiling approach for direct quantification of AR-V7 in peripheral whole blood without the need for CTC capture and to determine its potential for predicting treatment response in mCRPC patients.

Design, setting, and participants

Whole blood samples from a prospective biorepository of 85 mCRPC patients before treatment initiation with abiraterone (n = 56) or enzalutamide (n = 29) were analyzed via droplet digital polymerase chain reaction.

Outcome measurements and statistical analysis

The association of AR-V7 status with prostate-specific antigen (PSA) response defined by PSA decline ≥50% and with PSA–progression-free survival (PSA-PFS), clinical PFS, and overall survival (OS) was assessed.

Results and limitations

High AR-V7 expression levels in whole blood were detectable in 18% (15/85) of patients. No patient with high AR-V7 expression achieved a PSA response, and AR-V7 status was an independent predictor of PSA response in multivariable logistic regression analysis (p = 0.03). High AR-V7 expression was associated with shorter PSA-PFS (median 2.4 vs 3.7 mo; p < 0.001), shorter clinical PFS (median 2.7 vs 5.5 mo; p < 0.001), and shorter OS (median 4.0 vs. 13.9 mo; p < 0.001). On multivariable Cox regression analysis, high AR-V7 expression remained an independent predictor of shorter PSA-PFS (hazard ratio [HR] 7.0, 95% confidence interval [CI] 2.3–20.7; p < 0.001), shorter clinical PFS (HR 2.3, 95% CI 1.1–4.9; p = 0.02), and shorter OS (HR 3.0, 95% CI 1.4–6.3; p = 0.005).

Conclusions

Testing of AR-V7 mRNA levels in whole blood is a simple and promising approach to predict poor treatment outcome in mCRPC patients receiving abiraterone or enzalutamide.

Patient summary

We established a method for determining AR-V7 status in whole blood. This test predicted treatment resistance in patients with metastatic castration-resistant prostate cancer undergoing treatment with abiraterone or enzalutamide. Prospective validation is needed before application to clinical practice.



中文翻译:

去势抵抗性前列腺癌患者外周全血中的 AR-V7:与阿比特龙和恩杂鲁胺治疗特异性结果的相关性

背景

已经证明,循环肿瘤细胞 (CTC) 中雄激素受体剪接变体 7 (AR-V7) 的表达预示着接受阿比特龙或恩杂鲁胺治疗的转移性去势抵抗性前列腺癌 (mCRPC) 患者的治疗反应不佳。

客观的

开发一种实用且稳健的液体分析方法,用于在不需要 CTC 捕获的情况下直接定量外周全血中的 AR-V7,并确定其预测 mCRPC 患者治疗反应的潜力。

设计、设置和参与者

在开始使用阿比特龙 ( n  = 56) 或恩杂鲁胺 ( n  = 29) 进行治疗之前,来自 85 名 mCRPC 患者的前瞻性生物样本库的全血样本通过液滴数字聚合酶链反应进行了分析。

结果测量和统计分析

评估了 AR-V7 状态与由 PSA 下降≥50% 定义的前列腺特异性抗原 (PSA) 反应以及与 PSA 无进展生存 (PSA-PFS)、临床 PFS 和总生存 (OS) 的关联。

结果和限制

在 18% (15/85) 的患者中可检测到全血中的高 AR-V7 表达水平。没有高表达 AR-V7 的患者达到 PSA 反应,在多变量逻辑回归分析中,AR-V7 状态是 PSA 反应的独立预测因子 ( p  = 0.03)。AR-V7 高表达与更短的 PSA-PFS(中位 2.4 与 3.7 个月;p  < 0.001)、更短的临床 PFS(中位 2.7 与 5.5 个月;p  < 0.001)和更短的 OS(中位 4.0 与 13.9 个月;p  < 0.001)。在多变量 Cox 回归分析中,高 AR-V7 表达仍然是更短 PSA-PFS(风险比 [HR] 7.0,95% 置信区间 [CI] 2.3-20.7;p  < 0.001)、更短临床 PFS(HR 2.3)的独立预测因子, 95% CI 1.1–4.9;p  = 0.02)和更短的 OS(HR 3.0,95% CI 1.4–6.3;p  = 0.005)。

结论

检测全血中 AR-V7 mRNA 水平是一种简单且有前景的方法,可用于预测接受阿比特龙或恩杂鲁胺治疗的 mCRPC 患者的不良治疗结果。

患者总结

我们建立了一种确定全血中 AR-V7 状态的方法。该测试预测了接受阿比特龙或恩杂鲁胺治疗的转移性去势抵抗性前列腺癌患者的治疗耐药性。在应用于临床实践之前需要进行前瞻性验证。

更新日期:2017-08-14
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