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Cytoreductive Surgery in the Management of Renal Tumours: Rationale Current Evidence and Future Perspectives

机译:肾肿瘤管理中的细胞还原手术:理论基础当前证据和未来展望

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摘要

Renal cell carcinoma accounts for 3% of adult solid malignant tumours. Approximately 25% of the patients present with metastatic disease at presentation. In the era of immunotherapy (interferon alpha-2b and interleukin-2), studies showed significant survival benefit with cytoreductive nephrectomy (CRN) followed by interferon alpha-2b than interferon alpha 2-b alone. Introduction of targeted therapies (vascular endothelial growth factor receptor-tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors) in 2005 generated a great interest in the management of metastatic renal cell carcinoma (mRCC) as these drugs exhibited tumour shrinkage in the primary tumour as well as in the metastatic site/s. Though there is no level 1 evidence, many studies have shown the usefulness of cytoreductive nephrectomy along with targeted therapy as against to targeted therapy alone. This review is aimed at the rationale behind the cytoreductive nephrectomy in mRCC, the current evidence and what is in store for the future. A detailed search on the management of mRCC was carried out on MEDLINE, Embase, CANCERLIT and Cochrane Library databases using the key words “cytoreductive nephrectomy”, “immunotherapy” and “targeted therapy” since 1980 till 2015. Original articles, review articles, monograms, book chapters on metastatic renal cancer and textbooks on urologic oncology, oncology and urology were reviewed. Various international guidelines on this issue were also studied. An identical search was performed using the American Society of Clinical Oncology Abstract database. Trials in the progress or recently completed that were relevant to this paper were identified through clinicaltrials.gov. The latest information for new articles ahead of publication was last accessed in November 2015. CRN has remained an integral part to the management of metastatic renal cell carcinoma mainly for the patients with good performance status, life expectancy of more than 12 months and in the absence of adverse prognostic factors. It had shown measurable survival benefit in the era of immunotherapy (CRN + immunotherapy vs. immunotherapy alone). In the era of targeted therapy, many studies have shown significant survival benefit with CRN + targeted therapy. However, there is no clear level 1 evidence to support this. The ongoing trials (CARMENA and European Organisation for Research and Treatment of Cancer SURTIME) would perhaps guide us in the way in which we should manage mRCC disease in the future. Maybe we may find some answers on the issues of the effectiveness of targeted therapy, the timing of CRN and sequencing these treatment arms once the results of these ongoing and future trials are through.
机译:肾细胞癌占成人实体恶性肿瘤的3%。就诊时约有25%的患者患有转移性疾病。在免疫疗法时代(干扰素α-2b和白介素2),研究显示,细胞减灭性肾切除术(CRN)继之以干扰素α-2b比单独的干扰素α2-b具有明显的生存获益。 2005年引入靶向疗法(血管内皮生长因子受体酪氨酸激酶抑制剂,雷帕霉素抑制剂的哺乳动物靶标)引起了对转移性肾细胞癌(mRCC)治疗的极大兴趣,因为这些药物在原发性肿瘤中也表现出肿瘤缩小如在转移部位。尽管尚无1级证据,但许多研究表明,细胞减灭性肾切除术与靶向治疗相比仅针对靶向治疗是有用的。这项审查的目的是在mRCC中进行细胞还原性肾切除术的基本原理,当前证据以及将来的用途。自1980年至2015年,在MEDLINE,Embase,CANCERLIT和Cochrane图书馆数据库中使用“细胞减少性肾切除术”,“免疫疗法”和“靶向疗法”作为关键词,对mRCC的管理进行了详细的搜索。回顾了有关转移性肾癌的书籍章节以及有关泌尿科肿瘤学,肿瘤学和泌尿科的教科书。还研究了有关此问题的各种国际准则。使用美国临床肿瘤学会摘要数据库进行了相同的搜索。通过clinicaltrials.gov确定了与本文相关的正在进行或近期完成的试验。出版前最新文章的最新信息是在2015年11月获得的。CRN仍是转移性肾细胞癌治疗不可或缺的部分,主要针对表现良好,预期寿命超过12个月且无此情况的患者不良预后因素。在免疫疗法时代(CRN +免疫疗法与单独的免疫疗法),它显示出可衡量的生存获益。在靶向治疗时代,许多研究表明CRN +靶向治疗具有明显的生存获益。但是,尚无明确的1级证据支持这一点。正在进行的试验(CARMENA和欧洲癌症研究和治疗组织SURTIME)也许会指导我们将来应对mRCC疾病的方式。一旦这些正在进行的和将来的试验结果通过,我们也许可以找到关于靶向治疗的有效性,CRN的时机以及对这些治疗方案进行排序的问题的答案。

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