Department of Urology, Southern General Hospital, 1345 Govan Road, Glasgow, G51 4TF, UK.
Mol Diagn Ther. 2009;13(5):277-81. doi: 10.1007/BF03256333.
Treatment of metastatic renal cell cancer (RCC) has entered a new paradigm since the development of tyrosine kinase inhibitors such as sorafenib (Nexavar) and sunitinib (Sutent). Despite these advances, immunotherapy, the traditional mainstay of treatment, is not yet obsolete. Immunotherapy offers the possibility of a complete response for a small number of patients with favorable disease factors. However, immunotherapy is a toxic treatment, with a significant impact on quality of life in comparison with a relatively modest survival advantage for most. As such, the search for a biomarker to select patients for immunotherapy and to monitor their progress still remains a clinical and research goal for those involved in treating patients with metastatic renal cancer. At present, performance status and a number of prognostic scores incorporating performance status and laboratory variables are the most widely used indicators of suitability for immunotherapy. More recently, the histological expression of carbonic anhydrase IX has been reported as a biomarker of response to interleukin (IL)-2 immunotherapy. C-reactive protein (CRP) is an acute-phase protein synthesized as part of the systemic inflammatory response. It is readily measured by standardized assays and is reliable, without variability for age, sex, or bodyweight. The presence of an elevated CRP is a prognostic indicator in a number of solid tumors, both in localized and metastatic disease. In advanced renal cancer, the Glasgow Prognostic Score, which is based on elevated CRP and low albumin, has shown prognostic value. CRP is also superior to the widely used performance status in predicting survival for patients treated with either interferon (IFN)-alpha or IL-2. As such, CRP is an increasingly exciting biomarker for predicting outcomes in immunotherapy. Currently, no other biomarker has been applicable for use in both IFNalpha and IL-2 immunotherapy. More recently, changes in CRP kinetics have shown promise as a predictive tool, although more research is required. Use of CRP as a biomarker can improve stratification of patients with metastatic renal cancer, allowing the patients less likely to benefit from immunotherapy to avoid a potentially toxic treatment. The ongoing selection of patients based on biomarkers should enable continued research on the optimum dose and timing of immunotherapy while managing toxicity and optimizing outcomes.
自索拉非尼（Nexavar）和舒尼替尼（Sutent）等酪氨酸激酶抑制剂问世以来，转移性肾细胞癌（RCC）的治疗已经进入了一个新的模式。尽管取得了这些进展，但免疫疗法，作为传统的治疗基础，尚未过时。免疫疗法为少数具有良好疾病因素的患者提供了完全缓解的可能性。然而，免疫疗法是一种有毒的治疗方法，与大多数患者相对较小的生存优势相比，对生活质量的影响显著。因此，寻找一种生物标志物来选择接受免疫治疗的患者并监测他们的进展，仍然是治疗转移性肾肿瘤患者的临床和研究目标。目前，表现状态和许多包含表现状态和实验室变量的预后评分是最广泛用于免疫治疗适用性的指标。最近，碳酸酐酶 IX 的组织学表达已被报道为白细胞介素（IL）-2 免疫治疗反应的生物标志物。C 反应蛋白（CRP）是作为全身炎症反应的一部分合成的急性期蛋白。它可以通过标准化检测进行容易测量，并且可靠，不受年龄、性别或体重的影响。在许多实体瘤中，包括局限性和转移性疾病，CRP 升高是一种预后指标。在晚期肾细胞癌中，基于 CRP 升高和白蛋白降低的格拉斯哥预后评分显示出预后价值。CRP 在预测接受干扰素（IFN）-α或 IL-2 治疗的患者的生存方面也优于广泛使用的表现状态。因此，CRP 是预测免疫治疗结果的一个令人兴奋的生物标志物。目前，没有其他生物标志物可用于 IFNalpha 和 IL-2 免疫治疗。最近，CRP 动力学的变化显示出作为预测工具的潜力，尽管还需要更多的研究。CRP 作为生物标志物的使用可以改善转移性肾细胞癌患者的分层，使不太可能从免疫治疗中获益的患者避免潜在的毒性治疗。基于生物标志物的患者选择的持续进行应能使我们继续研究免疫治疗的最佳剂量和时机，同时管理毒性并优化结果。
