Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
Eur Urol. 2012 Oct;62(4):685-95. doi: 10.1016/j.eururo.2012.01.020. Epub 2012 Jan 23.
We recently identified apolipoprotein A2 (ApoA2) and serum amyloid α (SAA) as independent prognosticators in metastatic renal cell carcinoma (mRCC) patients, thereby improving the accuracy of the Memorial-Sloan Kettering Cancer Center (MSKCC) model.
Validate these results prospectively in a separate cohort of mRCC patients treated with tyrosine kinase inhibitors (TKIs).
DESIGN, SETTING, AND PARTICIPANTS: For training we used 114 interferon-treated mRCC patients (inclusion 2001-2006). For validation we studied 151 TKI-treated mRCC patients (inclusion 2003-2009).
Using Cox proportional hazards regression analysis, SAA and ApoA2 were associated with progression-free survival (PFS) and overall survival (OS). In 72 TKI-treated patients, SAA levels were analyzed longitudinally as a potential early marker for treatment effect.
Baseline ApoA2 and SAA levels significantly predicted PFS and OS in the training and validation cohorts. Multivariate analysis identified SAA in both separate patient sets as a robust and independent prognosticator for PFS and OS. In contrast to our previous findings, ApoA2 interacted with SAA in the validation cohort and did not contribute to a better predictive accuracy than SAA alone and was therefore excluded from further analysis. According to the tertiles of SAA levels, patients were categorized in three risk groups, demonstrating accurate risk prognostication. SAA as a single biomarker showed equal prognostic accuracy when compared with the multifactorial MSKCC risk mode. Using receiver operating characteristic analysis, SAA levels >71 ng/ml were designated as the optimal cut-off value in the training cohort, which was confirmed for its significant sensitivity and specificity in the validation cohort. Applying SAA >71 ng/ml as an additional risk factor significantly improved the predictive accuracy of the MSKCC model in both independent cohorts. Changes in SAA levels after 6-8 wk of TKI treatment had no value in predicting treatment outcome.
SAA but not ApoA2 was shown to be a robust and independent prognosticator for PFS and OS in mRCC patients. When incorporated in the MSKCC model, SAA showed additional prognostic value for patient management.
我们最近发现载脂蛋白 A2（ApoA2）和血清淀粉样蛋白 A（SAA）是转移性肾细胞癌（mRCC）患者独立的预后指标，从而提高了 Memorial-Sloan Kettering 癌症中心（MSKCC）模型的准确性。
在接受酪氨酸激酶抑制剂（TKI）治疗的 mRCC 患者的另一个队列中前瞻性验证这些结果。
设计、地点和参与者：为了进行训练，我们使用了 114 例接受干扰素治疗的 mRCC 患者（纳入时间为 2001-2006 年）。为了验证，我们研究了 151 例接受 TKI 治疗的 mRCC 患者（纳入时间为 2003-2009 年）。
使用 Cox 比例风险回归分析，SAA 和 ApoA2 与无进展生存期（PFS）和总生存期（OS）相关。在 72 例接受 TKI 治疗的患者中，作为治疗效果的潜在早期标志物，对 SAA 水平进行了纵向分析。
在训练和验证队列中，基线 ApoA2 和 SAA 水平显著预测 PFS 和 OS。多变量分析确定 SAA 在两个独立的患者组中是 PFS 和 OS 的一个强大而独立的预后指标。与我们之前的发现相反，ApoA2 在验证队列中与 SAA 相互作用，并且没有比单独的 SAA 提供更好的预测准确性，因此被排除在进一步的分析之外。根据 SAA 水平的三分位数，患者被分为三个风险组，证明了准确的风险预测。SAA 作为单一生物标志物在预测准确性方面与多因素 MSKCC 风险模型相当。使用接收者操作特征分析，将 SAA 水平>71ng/ml 定义为训练队列中的最佳截断值，该值在验证队列中得到了显著的灵敏度和特异性的确认。在两个独立队列中，将 SAA>71ng/ml 作为附加风险因素显著提高了 MSKCC 模型的预测准确性。TKI 治疗 6-8 周后 SAA 水平的变化对预测治疗结果没有价值。
SAA 而不是 ApoA2 是 mRCC 患者 PFS 和 OS 的强大而独立的预后指标。当纳入 MSKCC 模型时，SAA 为患者管理提供了额外的预后价值。
