Wang Jiaxin, Zhang Yucong, Wei Chao, Gao Xintao, Yuan Penghui, Gan Jiahua, Li Rui, Liu Zhuo, Wang Tao, Wang Shaogang, Liu Jihong, Liu Xiaming
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Oncol. 2020 Nov 30;10:562504. doi: 10.3389/fonc.2020.562504. eCollection 2020.
The 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.
We searched the PubMed, Embase, and MEDLINE databases by using the keywords and 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.
A 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; < 0.001), shorter PFS (HR 2.56, 95% CI 1.80-3.64; < 0.001) and shorter OS (HR 4.28, 95% CI 2.92-6.27; < 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; = 0.001) and shorter OS than AR-V7-negative patients (HR 1.60, 95% CI 1.02-2.53; = 0.043), there was no significant difference in PFS (HR 1.05, 95% CI 0.74-1.49; = 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; < 0.001); There was no significant difference among AR-V7-negative patients (HR 1.30, 95% CI 0.64-2.62; = 0.47).
AR-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.
雄激素受体剪接变体7（AR-V7）对转移性去势抵抗性前列腺癌（mCRPC）治疗反应的预后价值仍不明确。在本研究中，我们旨在综合评估AR-V7状态对接受雄激素受体信号抑制剂（ARSis）和化疗的mCRPC患者治疗反应的预后价值的相关研究。
我们通过使用关键词在PubMed、Embase和MEDLINE数据库中进行检索，以识别2019年9月25日前发表的相关研究。主要结局为前列腺特异性抗原（PSA）反应、无进展生存期（PFS）和总生存期（OS）。使用随机效应模型计算合并比值比（OR）和风险比（HR）以及95%置信区间（CI）。使用纽卡斯尔-渥太华质量评估量表评估纳入研究的质量。
共纳入来自21项研究的1545例患者。对于接受ARSis治疗的mCRPC患者，AR-V7阳性患者的PSA反应率较低（OR 6.01，95%CI 2.88-12.51；P<0.001），PFS较短（HR 2.56，95%CI 1.80-3.64；P<0.001），OS也较短（HR 4.28，95%CI 2.92-6.27；P<0.001），均低于AR-V7阴性患者。尽管接受化疗的AR-V7阳性患者的PSA反应率也低于AR-V7阴性患者（OR 2.23，95%CI 1.38-3.62；P=0.001），OS也较短（HR 1.60，95%CI 1.02-2.53；P=0.043），但两组之间的PFS无显著差异（HR 1.05，95%CI 0.74-1.49；P=0.796）。此外，接受ARSis治疗的AR-V7阳性患者的中位OS短于接受化疗的患者（HR 3.50，95%CI 1.98-6.20；P<0.001）；AR-V7阴性患者之间无显著差异（HR 1.30，95%CI 0.64-2.62；P=0.47）。
AR-V7是mCRPC患者治疗抵抗的潜在生物标志物。AR-V7阳性的mCRPC患者接受ARSis治疗时的治疗结局比AR-V7阴性患者差。AR-V7阳性患者接受紫杉烷治疗时的结局比接受ARSis治疗时更好。此外，AR-V7状态预测治疗结局的能力因检测方法不同而有所差异。治疗前检测AR-V7对mCRPC患者治疗方式的选择很重要。
