Taplin Mary-Ellen, George Daniel J, Halabi Susan, Sanford Ben, Febbo Philip G, Hennessy Kristen T, Mihos Christos G, Vogelzang Nicholas J, Small Eric J, Kantoff Philip W
Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Urology. 2005 Aug;66(2):386-91. doi: 10.1016/j.urology.2005.03.040.
To test the hypothesis that chromogranin A (CgA) levels are prognostic in patients with metastatic hormone-refractory prostate cancer (HRPC). The extent of neuroendocrine differentiation in prostate cancer correlates with aggressive disease and with progression to HRPC. Plasma CgA levels in patients with prostate cancer may reflect the extent of the tumor neuroendocrine phenotype.
Pretreatment plasma was collected from 390 patients with metastatic HRPC enrolled in the Cancer and Leukemia Group B (CALGB) 9480 trial, a study of three different doses of suramin. Plasma CgA levels were determined in 321 samples in duplicate using a quantitative sandwich immunoassay. The proportional hazards model was used to assess the prognostic significance of CgA in predicting overall survival.
The median plasma CgA level was 12 U/L (interquartile range 7.7 to 19.3). In univariate analysis, plasma CgA correlated inversely with survival times, with a survival time of 17 months for low CgA (less than 12 U/L, 95% CI 14 to 19) compared with 11 months for high CgA (95% CI 8 to 14, P = 0.014) and at all exploratory cutpoints, including CgA of 9.5 U/L or less versus greater than 9.5 U/L, with survival of 19 months compared with 12 months (P = 0.0015). In multivariate models (adjusting for performance status, prostate-specific antigen, and lactate dehydrogenase), the plasma CgA levels remained predictive of overall survival.
These results support the hypothesis that serum CgA levels correlate with outcome in patients with HRPC, although the clinical significance needs to be established in confirmatory studies before incorporation of CgA measurements in clinical practice.
检验嗜铬粒蛋白A（CgA）水平对转移性激素难治性前列腺癌（HRPC）患者具有预后价值这一假设。前列腺癌中神经内分泌分化程度与侵袭性疾病以及进展为HRPC相关。前列腺癌患者的血浆CgA水平可能反映肿瘤神经内分泌表型的程度。
从参与癌症与白血病B组（CALGB）9480试验（一项关于三种不同剂量苏拉明的研究）的390例转移性HRPC患者中收集预处理血浆。使用定量夹心免疫测定法对321份样本的血浆CgA水平进行了两次测定。采用比例风险模型评估CgA在预测总生存方面的预后意义。
血浆CgA水平中位数为12 U/L（四分位间距7.7至19.3）。在单因素分析中，血浆CgA与生存时间呈负相关，低CgA水平（低于12 U/L，95%可信区间14至19）患者的生存时间为17个月，而高CgA水平（95%可信区间8至14，P = 0.014）患者的生存时间为11个月；在所有探索性切点处，包括CgA为9.5 U/L及以下与大于9.5 U/L相比，生存时间分别为19个月和12个月（P = 0.0015）。在多变量模型中（校正了体能状态、前列腺特异性抗原和乳酸脱氢酶），血浆CgA水平仍然是总生存的预测指标。
这些结果支持血清CgA水平与HRPC患者的预后相关这一假设，不过在将CgA检测纳入临床实践之前，还需要在验证性研究中确定其临床意义。
