The Institute for Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK.
The Institute for Cancer Research, London, UK.
Eur Urol. 2019 Nov;76(5):676-685. doi: 10.1016/j.eururo.2019.04.006. Epub 2019 Apr 27.
Detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumour cells (CTCs) is associated with worse outcome in metastatic castration-resistant prostate cancer (mCRPC). However, studies rarely report comparisons with CTC counts and biopsy AR-V7 protein expression.
To determine the reproducibility of AdnaTest CTC AR-V7 testing, and associations with clinical characteristics, CellSearch CTC counts, tumour biopsy AR-V7 protein expression and overall survival (OS).
DESIGN, SETTING, AND PARTICIPANTS: CTC AR-V7 status was determined for 227 peripheral blood samples, from 181 mCRPC patients with CTC counts (202 samples; 136 patients) and matched mCRPC biopsies (65 samples; 58 patients).
CTC AR-V7 status was associated with clinical characteristics, CTC counts, and tissue biopsy AR-V7 protein expression. The association of CTC AR-V7 status and other baseline variables with OS was determined.
Of the samples, 35% were CTC+/AR-V7+. CTC+/AR-V7+ samples had higher CellSearch CTC counts (median CTC; interquartile range [IQR]: 60, 19-184 vs 9, 2-64; Mann-Whitney test p<0.001) and biopsy AR-V7 protein expression (median H-score, IQR: 100, 63-148 vs 15, 0-113; Mann-Whitney test p=0.004) than CTC+/AR-V7- samples. However, both CTC- (63%) and CTC+/AR-V7- (62%) patients had detectable AR-V7 protein in contemporaneous biopsies. After accounting for baseline characteristics, there was shorter OS in CTC+/AR-V7+ patients than in CTC- patients (hazard ratio [HR] 2.13; 95% confidence interval [CI] 1.23-3.71; p=0.02); surprisingly, there was no evidence that CTC+/AR-V7+ patients had worse OS than CTC+/AR-V7- patients (HR 1.26; 95% CI 0.73-2.17; p=0.4). A limitation of this study was the heterogeneity of treatment received.
Studies reporting the prognostic relevance of CTC AR-V7 status must account for CTC counts. Discordant CTC AR-V7 results and AR-V7 protein expression in matched, same-patient biopsies are reported.
Liquid biopsies that determine circulating tumour cell androgen receptor splice variant-7 status have the potential to impact treatment decisions in metastatic castration-resistant prostate cancer patients. Robust clinical qualification of these assays is required before their routine use.
循环肿瘤细胞（CTC）中雄激素受体剪接变体-7（AR-V7）mRNA 的检测与转移性去势抵抗性前列腺癌（mCRPC）的预后较差相关。然而，研究很少报告与 CTC 计数和活检 AR-V7 蛋白表达的比较。
确定 AdnaTest CTC AR-V7 检测的可重复性，以及与临床特征、CellSearch CTC 计数、肿瘤活检 AR-V7 蛋白表达和总生存期（OS）的相关性。
设计、地点和参与者：对 181 名 mCRPC 患者的 227 份外周血样本（202 份样本；136 名患者）和匹配的 mCRPC 活检（65 份样本；58 名患者）进行了 CTC AR-V7 状态的检测。
检测了 CTC AR-V7 状态与临床特征、CTC 计数和组织活检 AR-V7 蛋白表达的相关性。确定了 CTC AR-V7 状态与其他基线变量与 OS 的关系。
在这些样本中，有 35%为 CTC+/AR-V7+。与 CTC+/AR-V7-样本相比，CTC+/AR-V7+样本的 CellSearch CTC 计数更高（中位数 CTC；四分位距 [IQR]：60，19-184 比 9，2-64；曼-惠特尼检验，p<0.001），活检 AR-V7 蛋白表达（中位数 H 评分，IQR：100，63-148 比 15，0-113；曼-惠特尼检验，p=0.004）更高。然而，在同期活检中，CTC-（63%）和 CTC+/AR-V7-（62%）患者都有可检测到的 AR-V7 蛋白。在考虑了基线特征后，与 CTC-患者相比，CTC+/AR-V7+患者的 OS 更短（风险比 [HR] 2.13；95%置信区间 [CI] 1.23-3.71；p=0.02）；令人惊讶的是，没有证据表明 CTC+/AR-V7+患者的 OS 比 CTC+/AR-V7-患者更差（HR 1.26；95%CI 0.73-2.17；p=0.4）。本研究的一个局限性是接受治疗的异质性。
报告 CTC AR-V7 状态预后相关性的研究必须考虑 CTC 计数。报告了同一患者配对活检中存在不一致的 CTC AR-V7 结果和 AR-V7 蛋白表达。
确定循环肿瘤细胞雄激素受体剪接变体-7 状态的液体活检有可能影响转移性去势抵抗性前列腺癌患者的治疗决策。在常规使用这些检测方法之前，需要对其进行严格的临床验证。
