Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer
Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer
复制标题
DOI：
10.1158/1078-0432.ccr-08-0872
复制
发表时间：
2008-10-01
影响因子：
11.5
通讯作者：
Raghavan, Derek
中科院分区：
文献类型：
--
作者：
de Bono, Johann S.;Scher, Howard I.;Raghavan, Derek
目的：一种计数循环肿瘤细胞（CTC）的方法已获得监管批准。这项前瞻性研究的主要目的是确定去势抵抗性前列腺癌（CRPC）治疗后CTC计数与总生存期（OS）之间的关系。次要目标包括确定的预后效用CTC测量开始治疗前，CTC前列腺特异性抗原（PSA）的变化和CIS在这些和其他时间点的关系，并在这些和其他timepoint.Experimental设计：血液抽取从CRPC患者进行性疾病开始一个新的化疗线治疗前和每月之后。将患者分为预定的有利或不利组（= 5CTC/7.5mL）。结果：276例入选患者中有231例（84%）可评价。治疗前CTC不佳的患者（57%）CS较短（中位OS，11.5 vs 21.7个月;考克斯风险比，3.3; P < 0.0001）。不利的治疗后CTC计数也预测2 - 5、6 - 8、9 - 12和13 - 20周的OS较短（中位OS，6.7-9.5 vs 19.6-20.7个月;考克斯风险比，3.6-6.5; P < 0.0001）。在所有时间点，CTC计数预测OS优于PSA减量算法; CTC的受试者工作曲线下面积为81%至87%，PSA降低30%时为58%至68%（P = 0.0218）。（a）基线CTC不利的患者转化为CTC有利的患者预后改善（6.8至21.3个月）;（B）基线CTC有利的患者转化为CTC不利的患者预后恶化（>26至9.3个月）。这些数据导致美国食品药品监督管理局批准该测定法用于评价CRPC。
Purpose: A method for enumerating circulating tumor cells (CTC) has received regulatory clearance. The primary objective of this prospective study was to establish the relationship between posttreatment CTC count and overall survival (OS) in castration-resistant prostate cancer (CRPC). Secondary objectives included determining the prognostic utility of CTC measurement before initiating therapy, and the relationship of CTC to prostate-specific antigen (PSA) changes and CIS at these and other time points.Experimental Design: Blood was drawn from CRPC patients with progressive disease starting a new line of chemotherapy before treatment and monthly thereafter. Patients were stratified into predetermined Favorable or Unfavorable groups (= 5 CTC/7.5mL).Results: Two hundred thirty-one of 276 enrolled patients (84%) were evaluable. Patients with Unfavorable pretreatment CTC (57%) had shorter CS (median OS, 11.5 versus 21.7 months; Cox hazard ratio, 3.3; P < 0.0001). Unfavorable posttreatment CTC counts also predicted shorter OS at 2 to 5, 6 to 8, 9 to 12, and 13 to 20 weeks (median OS, 6.7-9.5 versus 19.6-20.7 months; Cox hazard ratio, 3.6-6.5; P < 0.0001). CTC counts predicted OS better than PSA decrement algorithms at all time points; area under the receiver operator curve for CTC was 81% to 87% and 58% to 68% for 30% PSA reduction (P = 0.0218). Prognosis for patients with (a) Unfavorable baseline CTC who converted to Favorable CTC improved (6.8 to 21.3 months); (b) Favorable baseline CTC who converted to Unfavorable worsened (>26 to 9.3 months).Conclusions: CTC are the most accurate and independent predictor of OS in CRPC. These data led to Food and Drug Administration clearance of this assay for the evaluation of CRPC.