Kienel Alexandra, Porres Daniel, Heidenreich Axel, Pfister David
Department of Urology, University Hospital, RWTH Aachen University, Aachen, Germany.
Department of Urology, University Hospital, RWTH Aachen University, Aachen, Germany.
J Urol. 2015 Oct;194(4):966-71. doi: 10.1016/j.juro.2015.04.055. Epub 2015 Apr 18.
Chemotherapy is an integral part of the treatment of castration resistant prostate cancer. With the introduction of new drugs the need to identify nonresponders is increasing. To our knowledge there are no prognostic parameters to date for use upon the initiation of any treatment.
cfDNA was isolated from a serum specimen before chemotherapy. Its value was correlated to recurrence-free and overall survival using Kaplan-Meier curves. Univariate and multivariate Cox regression analysis was performed to identify independent predictors.
Of 59 men 48 (81.4%) had a measurable prostate specific antigen decrease from baseline. Median followup was 15.0 months (range 2.4 to 58.4). The median cfDNA concentration in all men in this study was 27.71 ng/ml (mean 32.64). A threshold of 55.03 ng/ml was significantly associated with a poor prostate specific antigen response of less than 30% (p = 0.005). On univariate and multivariate analysis circulating cfDNA was an independent predictor of overall survival (HR 0.36, 95% CI 0.13-0.97, p = 0.044 and HR 0.34, 95% CI 0.12-0.91, p = 0.032, respectively). Limitations of the study are its retrospective character, and first and second line therapies.
Our trial shows that the cfDNA concentration before therapy may be a useful predictive and prognostic biomarker for prostate specific antigen response and survival.
化疗是去势抵抗性前列腺癌治疗的一个重要组成部分。随着新药的引入，识别无反应者的需求日益增加。据我们所知，目前在任何治疗开始时都没有可用的预后参数。
化疗前从血清标本中分离出游离DNA（cfDNA）。使用Kaplan-Meier曲线将其值与无复发生存率和总生存率相关联。进行单变量和多变量Cox回归分析以识别独立预测因素。
59名男性中，48名（81.4%）的前列腺特异性抗原从基线水平有可测量的下降。中位随访时间为15.0个月（范围2.4至58.4个月）。本研究中所有男性的cfDNA浓度中位数为27.71 ng/ml（平均值32.64）。55.03 ng/ml的阈值与小于30%的不良前列腺特异性抗原反应显著相关（p = 0.005）。在单变量和多变量分析中，循环cfDNA是总生存的独立预测因素（HR分别为0.36，95%CI 0.13 - 0.97，p = 0.044和HR 0.34，95%CI 0.12 - 0.91，p = 0.032）。本研究的局限性在于其回顾性特点以及一线和二线治疗。
我们的试验表明，治疗前的cfDNA浓度可能是前列腺特异性抗原反应和生存的有用预测和预后生物标志物。
