Dept. of Medical Oncology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD, Rotterdam, Netherlands.
Dept. of Medical Oncology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD, Rotterdam, Netherlands.
Eur J Cancer. 2019 Nov;121:48-54. doi: 10.1016/j.ejca.2019.08.005. Epub 2019 Sep 19.
The interpretation of the presence of AR-V7 in circulating tumour cells (CTCs) in men with metastatic castration-resistant prostate cancer (mCRPC) remains to be elucidated. AR-V7 may hold promise as a predictive biomarker, but there may be prognostic impact of AR-V7 positivity as well. To investigate the clinical value of AR-V7, we determined whether AR-V7 detection in CTCs in patients with mCRPC is associated with CTC counts and survival.
Between December 2011 and January 2019, three prospective clinical trials collected clinical data of patients with mCRPC, who progressed after docetaxel and/or enzalutamide or abiraterone. Baseline (and follow-up) blood samples were withdrawn determining CTC count and AR-V7 expression. The majority of patients started cabazitaxel as the next line of treatment after AR-V7 characterisation.
A total of 127 samples were evaluable for the analysis of CTC count versus AR-V7 status. Although an association was observed between AR-V7 and CTC count in all patients with mCRPC (p = 0.017), no such association was found in the prognostic unfavourable subgroup of patients with ≥5 CTCs. After adjusting for clinical prognostic factors, AR-V7 expression in CTCs was not associated with overall survival (hazard ratio = 1.33, 95% confidence interval = 0.81-2.15, p = 0.25).
We found that AR-V7 expression in CTCs had no additional prognostic value in patients with mCRPC, mostly treated with cabazitaxel. In patients with mCRPC with a predefined worse prognosis of a higher CTC count (≥5), a predictive biomarker is an important unmet medical need. Prospective trials should investigate whether AR-V7 detection in CTCs may guide treatment selection for these adverse prognosis patients.
在转移性去势抵抗性前列腺癌（mCRPC）男性患者的循环肿瘤细胞（CTC）中，AR-V7 的存在意义仍有待阐明。AR-V7 可能是一种有前途的预测生物标志物，但也可能具有阳性预后影响。为了研究 AR-V7 的临床价值，我们确定了 mCRPC 患者 CTC 中 AR-V7 的检测是否与 CTC 计数和生存相关。
在 2011 年 12 月至 2019 年 1 月期间，三项前瞻性临床试验收集了 mCRPC 患者的临床数据，这些患者在接受多西他赛和/或恩扎鲁胺或阿比特龙治疗后进展。在基线（和随访）时采集血液样本，以确定 CTC 计数和 AR-V7 表达。大多数患者在 AR-V7 特征确定后开始使用卡巴他赛作为下一线治疗。
共有 127 个样本可用于分析 CTC 计数与 AR-V7 状态之间的关系。尽管在所有 mCRPC 患者中观察到 AR-V7 与 CTC 计数之间存在关联（p=0.017），但在 CTC 计数≥5 的预后不良亚组中未发现这种关联。在调整了临床预后因素后，CTC 中的 AR-V7 表达与总生存无关（危险比=1.33，95%置信区间=0.81-2.15，p=0.25）。
我们发现，在主要接受卡巴他赛治疗的 mCRPC 患者中，CTC 中的 AR-V7 表达没有额外的预后价值。在 CTC 计数较高（≥5）的 mCRPC 患者中，预测性生物标志物是一个重要的未满足的医疗需求。前瞻性试验应研究在 CTC 中检测 AR-V7 是否可以指导这些预后不良患者的治疗选择。
