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The evolving role of surgery for advanced renal cell carcinoma in the era of molecular targeted therapy.

机译:在分子靶向治疗时代,晚期肾细胞癌手术的发展作用。

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PURPOSE: Thoughtful integration of surgical and medical approaches to metastatic renal cell carcinoma is paramount for maximizing disease control. Accomplishing this in the current era of targeted molecular therapies presents unique challenges and opportunities. MATERIALS AND METHODS: A systematic review of the MEDLINE and PubMed databases, and relevant urological and oncological journals was performed pertaining to cytoreductive nephrectomy, metastasectomy, targeted molecular therapies for renal cell carcinoma, and neoadjuvant and adjuvant approaches to the management of advanced renal cell carcinoma. RESULTS: Cytoreductive nephrectomy provides an overall survival advantage in select patients with metastatic renal cell carcinoma who receive subsequent interferon-alpha. However, cytokine therapies are now being supplanted by targeted molecular approaches that block the effects of vascular endothelial growth factor and other molecular events. Although cytoreductive nephrectomy remains a standard of care, limited insight into the biological effects of nephrectomy on mechanisms such as immunoregulation and angiogenesis precludes definitive statements about how to integrate surgery and targeted agents. Ongoing investigation involving basic science and translational research is required to optimize the integration of these approaches. Adjuvant and neoadjuvant vascular endothelial growth factor targeted approaches to renal cell carcinoma are now also being explored and the unique side effects of these agents, including potential effects on wound healing and vascular integrity, require careful consideration. CONCLUSIONS: Integrated approaches involving surgery and vascular endothelial growth factor targeted therapies hold much promise for the management of advanced renal cell carcinoma. Prospective clinical testing with vigilant attention to the risk-benefit ratio and thoughtful evaluation of biological correlates are required to optimize these approaches.
机译:目的:将手术和医学方法彻底整合到转移性肾细胞癌中,对于最大限度地控制疾病至关重要。在当前的靶向分子疗法时代实现这一目标提出了独特的挑战和机遇。材料与方法:对MEDLINE和PubMed数据库进行了系统评价,并进行了有关细胞减少性肾切除术,转移灶切除术,针对肾细胞癌的靶向分子疗法以及晚期肾脏细胞癌的新辅助治疗方法的相关泌尿科和肿瘤学期刊。结果:在选择接受转移性α干扰素治疗的转移性肾细胞癌患者中,细胞减少性肾切除术可提供总体生存优势。然而,现在已经通过靶向分子方法代替了细胞因子疗法,该分子方法阻断了血管内皮生长因子和其他分子事件的作用。尽管细胞减灭性肾切除术仍然是护理的标准,但是对肾切除术对诸如免疫调节和血管生成等机制的生物学作用的有限见解排除了关于如何整合手术和靶向药物的明确声明。需要进行涉及基础科学和转化研究的持续调查,以优化这些方法的集成。现在也正在探索针对肾细胞癌的辅助和新辅助血管内皮生长因子靶向方法,这些药物的独特副作用(包括对伤口愈合和血管完整性的潜在影响)需要仔细考虑。结论:涉及手术和血管内皮生长因子靶向治疗的综合方法对晚期肾细胞癌的治疗具有广阔的前景。需要进行前瞻性临床测试,并要谨慎关注风险收益率和对生物学相关因素的仔细评估,以优化这些方法。

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