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Abstract：
BACKGROUND: Baseline plasma androgen-receptor copy number (AR-CN) is a promising biomarker for metastatic castration-resistant prostate cancer (mCRPC) outcome and treatment response; however, the role of its longitudinal testing is unproven. We aimed to evaluate the prognostic role of AR-CN assessed before subsequent treatment lines in mCRPC patients.
METHODS: A subgroup analysis of a prospective multicenter biomarker trial (IRSTB030) was carried out. Plasma AR-CN status (classified as normal or gain, cut-off value = 2) was assessed with digital PCR before each treatment line.
RESULTS: Forty mCRPC patients receiving sequentially docetaxel, cabazitaxel and an AR signaling inhibitor (abiraterone or enzalutamide) were analyzed. At multivariate analysis, at each assessment overall survival (OS) was independently correlated with AR-CN status [first line: hazard ratio (HR) 4.1 [95% confidence interval (CI) 1.6-10.5]; second line: HR 2.4 (95% CI 1.1-5.3); third line: HR 2.1 (95% CI 1.0-4.3)] and median prostate-specific antigen [first line: HR 4.4 (95% CI 1.8-10.9); second line: HR 3.4 (95% CI 1.6-7.2); third line: HR 2.5 (95% CI 1.2-5.6)]. In the three subsequent assessments, AR-CN status changed from normal to gain in 15 (38%) patients. These patients had longer OS (47 months) compared with patients presenting AR-CN gain from first assessment (36 months), but shorter than those maintaining normal AR-CN (69 months) (P = 0.003).
CONCLUSIONS: Plasma AR-CN correlates with survival not only at baseline (before first treatment), but also in the assessments before the following lines. Interestingly, AR-CN status may change from normal to gain across subsequent treatments in a significant number of cases, identifying a group of patients with intermediate outcomes. Longitudinal assessment of AR-CN status could represent a promising method to capture mCRPC intrinsic heterogeneity and to improve clinical management.
METHODS: A subgroup analysis of a prospective multicenter biomarker trial (IRSTB030) was carried out. Plasma AR-CN status (classified as normal or gain, cut-off value = 2) was assessed with digital PCR before each treatment line.
RESULTS: Forty mCRPC patients receiving sequentially docetaxel, cabazitaxel and an AR signaling inhibitor (abiraterone or enzalutamide) were analyzed. At multivariate analysis, at each assessment overall survival (OS) was independently correlated with AR-CN status [first line: hazard ratio (HR) 4.1 [95% confidence interval (CI) 1.6-10.5]; second line: HR 2.4 (95% CI 1.1-5.3); third line: HR 2.1 (95% CI 1.0-4.3)] and median prostate-specific antigen [first line: HR 4.4 (95% CI 1.8-10.9); second line: HR 3.4 (95% CI 1.6-7.2); third line: HR 2.5 (95% CI 1.2-5.6)]. In the three subsequent assessments, AR-CN status changed from normal to gain in 15 (38%) patients. These patients had longer OS (47 months) compared with patients presenting AR-CN gain from first assessment (36 months), but shorter than those maintaining normal AR-CN (69 months) (P = 0.003).
CONCLUSIONS: Plasma AR-CN correlates with survival not only at baseline (before first treatment), but also in the assessments before the following lines. Interestingly, AR-CN status may change from normal to gain across subsequent treatments in a significant number of cases, identifying a group of patients with intermediate outcomes. Longitudinal assessment of AR-CN status could represent a promising method to capture mCRPC intrinsic heterogeneity and to improve clinical management.
摘要：
背景：基线血浆雄激素受体拷贝数（AR-CN）是转移性去势抵抗性前列腺癌（mCRPC）结果和治疗反应的有希望的生物标志物；然而，其纵向测试的作用未经证实。我们旨在评估mCRPC患者在后续治疗线之前评估的AR-CN的预后作用。
方法：进行前瞻性多中心生物标志物试验（IRSTB030）的亚组分析。血浆AR-CN状态（分类为正常或增益，在每个处理线之前，用数字PCR评估截断值=2）。
结果：40名mCRPC患者依次接受多西他赛，分析了卡巴他赛和AR信号传导抑制剂（阿比特龙或恩杂鲁胺）。在多变量分析中，每次评估时,总生存期(OS)与AR-CN状态[第一行:风险比(HR)4.1[95%可信区间(CI)1.6-10.5];第二行:HR2.4(95%CI1.1-5.3);第三行:HR2.1(95%CI1.0-4.3)]和中位前列腺特异性抗原[第一行:HR4.4(95%CI1.8-10.9);第二行:HR3.4(95%CI1.2-2.5);在随后的三次评估中，15例（38％）患者的AR-CN状态从正常变为增益。与首次评估（36个月）出现AR-CN增益的患者相比，这些患者的OS更长（47个月），但短于维持正常AR-CN（69个月）（P=0.003）。
结论：血浆AR-CN不仅与基线时（首次治疗前）的生存率相关，而且在评估之前还包括以下几行。有趣的是,在大量病例中，AR-CN状态可能会在后续治疗中从正常变为增益，确定一组具有中间结果的患者。AR-CN状态的纵向评估可能代表了捕获mCRPC内在异质性并改善临床管理的有希望的方法。
方法：进行前瞻性多中心生物标志物试验（IRSTB030）的亚组分析。血浆AR-CN状态（分类为正常或增益，在每个处理线之前，用数字PCR评估截断值=2）。
结果：40名mCRPC患者依次接受多西他赛，分析了卡巴他赛和AR信号传导抑制剂（阿比特龙或恩杂鲁胺）。在多变量分析中，每次评估时,总生存期(OS)与AR-CN状态[第一行:风险比(HR)4.1[95%可信区间(CI)1.6-10.5];第二行:HR2.4(95%CI1.1-5.3);第三行:HR2.1(95%CI1.0-4.3)]和中位前列腺特异性抗原[第一行:HR4.4(95%CI1.8-10.9);第二行:HR3.4(95%CI1.2-2.5);在随后的三次评估中，15例（38％）患者的AR-CN状态从正常变为增益。与首次评估（36个月）出现AR-CN增益的患者相比，这些患者的OS更长（47个月），但短于维持正常AR-CN（69个月）（P=0.003）。
结论：血浆AR-CN不仅与基线时（首次治疗前）的生存率相关，而且在评估之前还包括以下几行。有趣的是,在大量病例中，AR-CN状态可能会在后续治疗中从正常变为增益，确定一组具有中间结果的患者。AR-CN状态的纵向评估可能代表了捕获mCRPC内在异质性并改善临床管理的有希望的方法。
