Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola.
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola; Department of Medical and Surgical Sciences, Unit of Medical Oncology and Biomolecular Therapy, University of Foggia, Policlinico Riuniti, Foggia.
ESMO Open. 2023 Dec;8(6):102036. doi: 10.1016/j.esmoop.2023.102036. Epub 2023 Oct 20.
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.
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.
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).
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.
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）预后和治疗反应的有前途的生物标志物；然而，其纵向检测的作用尚未得到证实。我们旨在评估 mCRPC 患者后续治疗线前评估的 AR-CN 的预后作用。
对一项前瞻性多中心生物标志物试验（IRSTB030）进行了亚组分析。使用数字 PCR 在每个治疗线之前评估血浆 AR-CN 状态（分类为正常或增益，截断值= 2）。
分析了 40 名接受序贯多西他赛、卡巴他赛和 AR 信号抑制剂（阿比特龙或恩扎鲁胺）治疗的 mCRPC 患者。在多变量分析中，在每次评估时，总生存期（OS）均与 AR-CN 状态独立相关[一线：风险比（HR）4.1[95%置信区间（CI）1.6-10.5]；二线：HR 2.4（95%CI 1.1-5.3）；三线：HR 2.1（95%CI 1.0-4.3）]和中位前列腺特异性抗原[一线：HR 4.4（95%CI 1.8-10.9）；二线：HR 3.4（95%CI 1.6-7.2）；三线：HR 2.5（95%CI 1.2-5.6）]。在随后的三次评估中，15 名（38%）患者的 AR-CN 状态从正常变为增益。这些患者的 OS 更长（47 个月），与首次评估时 AR-CN 增益的患者相比（36 个月），但比维持正常 AR-CN 的患者（69 个月）短（P=0.003）。
血浆 AR-CN 与生存相关，不仅在基线（第一次治疗前），而且在后续线的评估中也是如此。有趣的是，在大量病例中，AR-CN 状态可能会从正常变为增益，从而确定一组中间结果的患者。AR-CN 状态的纵向评估可能是一种很有前途的方法，可以捕捉 mCRPC 的内在异质性并改善临床管理。
