外周血循环肿瘤细胞计数对去势抵抗性前列腺癌患者预后的预测作用

Prognostic value of circulating tumor cell enumeration for castration refractory prostate cancer

目的 探讨采用CellSearch检测系统进行的外周血循环肿瘤细胞（circulating tumor cell,CTC）计数对去势抵抗性前列腺癌（castration resistant prostate cancer,CRPC）患者预后的预测能力.方法 收集2013年1月至2014年6月就诊的92例初诊为CRPC患者的外周血,所有入组患者中位年龄69岁（53 ～ 85岁）,初诊PSA中位值19.1 ng/ml（2.6 ～273.0 ng/ml）,血红蛋白中位值124g/L（69～ 156 g/L）,碱性磷酸酶中位值87.0 U/L（29.0～2778.5 U/L）,乳酸脱氢酶中位值207 U/L（114～2467 U/L）,血白蛋白中位值44.0 g/L（32.3 ～52.2 g/L）.美国东部肿瘤协作组（ECOG）评分0～1分79例（85.9％）,≥2分13例（14.1％）.Gleason评分：＜8分36例（39.1％）,8分30例（32.6％）,＞8分26例（28.3％）.伴骨转移86例（93.5％）,其次为淋巴结转移29例（31.5％）.采用CellSearch检测系统对血标本进行CTC计数.同时收集5例健康人外周血作为对照组.92例CRPC患者中42例接受多西他赛＋泼尼松一线化疗,余50例因身体无法耐受或拒绝化疗而接受了酮康唑、雌激素或中药治疗.记录患者总体生存时间,绘制生存曲线,分析影响预后的危险因素.结果 本组92例CRPC患者的中位随访时间为16.2个月（7.0～26.0个月）,至末次随访死亡41例.对照组5例外周血中均未检测到CTC.92例CRPC患者按照外周血CTC计数分为2组,CTC＜5个组56例,中位生存时间25个月;CTC≥5个组36例,中位生存时间18个月,差异有统计学意义（P＜0.05）.单因素分析发现乳酸脱氢酶（P=0.02）、血红蛋白（P=0.00）、碱性磷酸酶（P=0.00）、血白蛋白（P=0.00）、ECOG评分（P=0.00）、外周血CTC计数（P=0.00）与患者预后相关.多因素分析发现仅血白蛋白（P=0.01）、ECOG评分（P=0.01）、外周血CTC计数（Jp=0.00）是影响CRPC患者预后的独立危险因素.根据患者是否接受多西他赛＋泼尼松一线化疗进行亚组分析,外周血CTC≥5个的患者均预后较差（P＜0.05）.结论 利用CellSearch检测系统对外周血的CTC计数可以协助判断CRPC患者的预后.

Objective To investigating the prognostic value of the CellSearch CTC enumeration system for the castration resistant prostate cancer （CRPC） patients.Methods From January 2013 to June 2014,92 CRPC patients＆#39;peripheral blood were collected and tested by CellSearch CTC detection system.The median age was 69 （range 53-85） years old and the median PSA was 19.1 （range 2.6-273.0） ng/ml.The median serum hemoglobin was 124（69-156）g/L,the serum alkaline phosphatase was 87.0 （29.0-2778.5） U/L,the serum lactate dehydrogenase was 207 （114-2467） U/ L and the serum albumin was 44.0 （32.3-52.2）g/L respectively.Among all the patients,39.1％ （36/92） was Gleason score below 8,32.6％ （30/ 92）was 8 and 28.3％ （26/92） was over 8.93.5％ （86/92） of the patients were diagnosed as bone metastasis and 31.5％ （29/92）as lymph node metastasis.Another 5 healthy volunteers with no evidence of tumor history were also tested as the control group.During the follow up,42 patients were treated with docetaxel plus prednisone as their first-line therapeutic regimen,and the remaining 50 patients who were intolerant to or refused chemotherapy were treated with ketoconazole,estrogen or traditional Chinese medicine.For the survival analysis,Kaplan-Meier plots were generated based on CTC enumeration at baseline and Log-rank test was conducted for calculating the survival difference between the groups.The independent prognostic factors were analyzed by the univariate and multivariate Cox analysis.Results At the time of follow-up,41 patients had died of prostate cancer with the median follow up of 16.2 mouths （range：7.0-26.0 months）.All the five patients were detected with no CTC.Ninety-two patients were divided into two groups based on CTC enumeration.Fifty-six patients were defined as favorable CTC counts group （CTC ＜ 5） with median follow up of 25 months and 36 as unfavorable CTC counts group （CTC ≥ 5） with median follow up of 18 months.Unfavorable CTC enumerations were predictive of shorter overall survival （Log-rank P =0.00）.In the univariate analysis,lactate dehydrogenase （P =0.02）,hemoglobin （P =0.00）,alkaline phosphatase（P =0.00）,serum albumin（P =0.01）,ECOG performance status（P =0.00） and CTC enumeration（P =0.00） were associated with prognosis of CRPC patients.A multivariate analysis indicated that only baseline serum alumin （P =0.01）,ECOG performance status（P =0.01） and CTC enumeration （P =0.00） were independent prognostic factors for overall survival.Subgroup analysis still support the notion that CTC ≥ 5 are indicative of poor prognosis regardless of receiving docetaxel plus prednisone as their first-line therapeutic regimen or not（P ＜ 0.05）.Conclusions In the current study,we validated that CTC enumeration could provide a useful prognostic determinant for CRPC patients.