Qu Fangfang, Xie Wanling, Nakabayashi Mari, Zhang Haitao, Jeong Seong Ho, Wang Xiaodong, Komura Kazumasa, Sweeney Christopher J, Sartor Oliver, Lee Gwo-Shu Mary, Kantoff Philip W
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Clin Cancer Res. 2017 Feb 1;23(3):726-734. doi: 10.1158/1078-0432.CCR-16-1070. Epub 2016 Aug 3.
We evaluated the association of PSA and androgen receptor splice variant-7 (AR-V7) transcript levels in patients' blood with time to treatment failure (TTF) and overall survival (OS) with abiraterone acetate and/or enzalutamide treatment in castration-resistant prostate cancer (CRPC) patients.
RNA levels of AR-V7 and PSA in peripheral blood collected before treatment were quantified using droplet digital-PCR in retrospective cohorts treated with abiraterone acetate (N = 81) or enzalutamide (N = 51) for CRPC. Multivariable Cox regression adjusted for known prognostic factors was used for analyses.
PSA transcripts were detected in 57% of abiraterone acetate-treated patients and in 63% of enzalutamide-treated patients. PSA-positive patients had a shorter TTF than PSA-negative patients [adjusted HR = 2.27 (95% confidence interval (CI) 1.26-4.10) and 2.60 (95% CI, 1.19-5.69); P = 0.006 and 0.017 in abiraterone acetate and enzalutamide cohorts, respectively]. Patients with a higher-AR-V7 transcript level had a shorter TTF with abiraterone acetate and enzalutamide in univariate analysis (median 8.0 months vs. 15.6 months, P = 0.046 in abiraterone acetate-cohort and 3.6 months vs. 5.6 months; P = 0.050 in enzalutamide cohort). In multivariable models, the association with TTF remained significant in the enzalutamide cohort (adjusted HR = 2.02; 95% CI, 1.01-4.05; P = 0.048), but statistically insignificant in the abiraterone acetate cohort. In both cohorts, we observed potential prognostic value of both PSA and AR-V7 RNA expression on OS; patients with detectable PSA transcripts and high AR-V7 predicted the poorest OS.
PSA and AR-V7 transcripts in blood potentially serve as biomarkers predicting TTF and OS with abiraterone acetate or enzalutamide treatment. If validated prospectively, their detection could be facilitated without isolation of circulating tumor cells. Clin Cancer Res; 23(3); 726-34. ©2016 AACR.
我们评估了去势抵抗性前列腺癌（CRPC）患者血液中前列腺特异性抗原（PSA）和雄激素受体剪接变异体7（AR-V7）转录水平与醋酸阿比特龙和/或恩杂鲁胺治疗的治疗失败时间（TTF）及总生存期（OS）之间的关联。
在接受醋酸阿比特龙（N = 81）或恩杂鲁胺（N = 51）治疗CRPC的回顾性队列中，使用液滴数字PCR对治疗前采集的外周血中AR-V7和PSA的RNA水平进行定量。采用针对已知预后因素进行调整的多变量Cox回归分析。
在接受醋酸阿比特龙治疗的患者中有57%检测到PSA转录本，恩杂鲁胺治疗的患者中有63%检测到。PSA阳性患者的TTF短于PSA阴性患者[调整后风险比（HR）分别为2.27（95%置信区间（CI）1.26 - 4.10）和2.60（95% CI，1.19 - 5.69）；在醋酸阿比特龙和恩杂鲁胺队列中P值分别为0.006和0.017]。在单变量分析中，AR-V7转录水平较高的患者接受醋酸阿比特龙和恩杂鲁胺治疗后的TTF较短（醋酸阿比特龙队列中分别为8.0个月对15.6个月，P = 0.046；恩杂鲁胺队列中为3.6个月对5.6个月，P = 0.050）。在多变量模型中，与TTF的关联在恩杂鲁胺队列中仍然显著（调整后HR = 2.02；95% CI，1.01 - 4.05；P = 0.048），但在醋酸阿比特龙队列中无统计学意义。在两个队列中，我们观察到PSA和AR-V7 RNA表达对OS均具有潜在的预后价值；检测到PSA转录本且AR-V7水平高的患者OS最差。
血液中的PSA和AR-V7转录本可能作为预测醋酸阿比特龙或恩杂鲁胺治疗TTF和OS的生物标志物。如果前瞻性验证成功，无需分离循环肿瘤细胞即可方便地进行检测。《临床癌症研究》；23(3)；726 - 34。©2016美国癌症研究协会。
