EAU指南解读之肾细胞癌RCC的治疗

Guidelines on renal cell carcinoma,EAU-Guidelines-Renal-Cell-Cancer-2015-v2,1、Introduction2、Treatment of localised RCC3、Treatment of locally advanced RCC4、Treatment of advanced/metastatic RCC5、Systemic therapy for advanced/metastatic RCC,Definition,Renal Cell Carcinoma, RCCRenal cell carcinoma is a kidney cancer that originates in the lining of the proximal convoluted tubule.RCC is the most common type of kidney cancer in adults.,Epidemiology,我国目前研究1 马建辉等收集了中国大陆19882002年15年间数据较齐全的11个研究单位的资料，19881992、19931997、19982002年3个时间段我国肾和泌尿系统其他恶性肿瘤的发病率分别为4.2610万、5.4010万、6.6310万人口，发病率呈现逐年上升趋势。我国上海、南京、广州分别排在第245(4.810万)、273(3.210万)、282(2.310万)。America2Renal cell carcinomas represent about 3% of all newly diagnosed visceral cancers in the United States and account for 85% of renal cancers in adults. Approximately 30,000 new cases /year and 12,000 deaths from the disease.,1马建辉,李呜,张思维等.中国部分市县肾癌及泌尿系其他恶性肿瘤发病趋势比较研究J.中华泌尿外科杂志,2009,30(8):511-514.DOI:10.3760/cma.j.issn.1000-6702.2009.08.002.2Jemal A, et al: Cancer statistics, 2008. CA Cancer J Clin 2008; 58:71.,Risk factors1 2,The most significant risk factor tobacco (Cigarette smokers have double the incidence of renal cell carcinoma) pipe and cigar smokers are also more susceptible. Additional risk factorsobesity (particularly in women)hypertension;unopposed estrogen therapy;exposure to asbestos, petroleum products, and heavy metals.,1McLaughlin JK, Lipworth L: Epidemiologic aspects of renal cell cancer. Semin Oncol 2000; 27:115.2 Moore LE, et al: Lifestyle factors, exposures, genetic susceptibility, and renal cell cancer risk: a review. Cancer Invest 2005; 23:240.,Diagnosis,1.Symptoms Physical examination:Physical examination has a limited role in RCC diagnosis Palpable abdominal mass; Palpable cervical lymphadenopathy; Non-reducing varicocele and bilateral lower extremity oedema, which suggests venous involvement. 2.Imaging investigations,Guidelines on Renal Cell Carcinoma. European Association of Urology 2015,Diagnosis,肾癌的临床诊断主要依靠影像学检查；实验室检查作为对患者术前一般状况、肝肾功能以及预后判定的评价指标；确诊则需依靠病理学检查。1推荐必须包括的实验室检查项目：尿素氮、肌酐、肝功能、全血细胞计数、血红蛋白、血钙、血糖、红细胞沉降率、碱性磷酸酶和乳酸脱氢酶(推荐分级C)2推荐必须包括的影像学检查项目：腹部B超或彩色多普勒超声；胸部X线片(正、侧位)、腹部CT平扫和增强扫描(碘过敏试验阴性、无相关禁忌证者)；腹部CT平扫和增强扫描及胸部X线片是术前临床分期的主要依据(推荐分级A）3推荐参考选择的影像学检查项目：KUB：可为开放性手术选择手术切口提供帮助核素肾图或IVU：可用于未行CT增强扫描，无法评价对侧肾功能者核素骨显像：碱性磷酸酶高、有相应骨症状或临床分期期的患者(证据水平I b)胸部CT扫描：胸部x线片有可疑结节、临床分期期的患者(证据水平I b)头部MRI、CT扫描：有头痛或相应神经系统症状患者(证据水平T b)腹部MRI扫描：肾功能不全、超声波检查或CT检查提示下腔静脉瘤栓患者(证据水平I b)。4有条件地区及患者选择的影像学检查项目：肾超声造影、螺旋CT及MRI扫描：主要用于肾癌的诊断和鉴别诊断正电子发射断层扫描(PET)或PETCT：检查费用昂贵，主要用于发现远处转移病灶以及对化疗、细胞因子治疗、分子靶向治疗或放疗的疗效评定。,肾细胞癌诊断治疗指南编写组.肾细胞癌诊断治疗指南(2008年第一版)J.中华泌尿外科杂志,2009,30(1):63-69.,Guidelines on Renal Cell Carcinoma. European Association of Urology 2015,Staging,Treatment of localised RCC (T1-2N0M0),For this Guidelines version, an updated search was performed up to May 31 st , 2013.,Surgical treatment,AdrenalectomyPartial nephrectomy (PN) VS radical nephrectomy (RN)Lymph node dissection for clinically negative lymph nodes (cN0)Embolisation：In patients unfit for surgery, or with non-resectable disease, embolisation can control symptoms, including gross haematuria or flank pain,Surgical treatment,Surgical treatment,Radical nephrectomy,Laparoscopic vs Open RN,Radical nephrectomy,Hand-assisted vs standerd laparoscopic RN,Partial nephrectomy,Laparoscopic vs Open PN,Conclusion and Recommendations,Laparoscopic RN:Lower morbidity, similar oncological outcomesT1: PNT2 or localised masses not treatable by PN: Laparoscopic RN,Therapeutic approaches as alternatives to surgery,Population-based analyses show a significantly lower cancer-specific mortality for patients treated with surgery compared to non-surgical management for tumors 75 years).,SurveillanceActive surveillance is defined as the initial monitoring of tumour size by serial abdominal imaging (US, CT, or MRI) with delayed intervention reserved for tumours showing clinical progression during follow-up.Ablative therapiesCryoablation(冷冻消融术)Radiofrequency ablation(射频消融术)Others：microwave ablation, laser ablation, and high-intensity focused US ablation.,Recommendations,Treatment of locally advanced RCC,Clinically positive lymph nodes (cN+)Locally advanced unresectable RCCRCC with venous thrombus,Clinically positive lymph nodes (cN+),LND is justifiedBut the extent of LND is controversial,Locally advanced unresectable RCC,Embolisation can control symptoms gross haematuria or flank painThe effect of neoadjuvant targeted therapy to downsize tumours is unknown.,RCC with venous thrombus,Traditionally undergo surgery to remove the kidney and tumour thrombusPre-operative embolisation(T3 RCC )（increasing operating time,blood loss, hospital stay and peri-operative mortality） The role of IVC filters and bypass procedures remain uncertain,Adjuvant therapy,Several RCTs of adjuvant sunitinib,sorafenib, pazopanib, axitinib and everolimus are ongoing. At present, there is no evidence for the use of adjuvant VEGF-R or mTOR inhibitors.There is no indication for adjuvant therapy following surgery.,Treatment of Advanced/Metastatic Renal Cell Carcinoma,Contents,What is Advanced/Metastatic Renal Cell Carcinoma (RCC)?How to Treat it?,What is Advanced/Metastatic Renal Cell Carcinoma,How to Treat it?,How to treat the primary lesion？How to deal with the metastases of RCC?,How to Treat it?,Protocol 1: Cytoreductive nephrectomy combined with interferon-alpha. Protocol 2: Cytoreductive nephrectomy with simultaneous complete resection of a single metastasis or oligometastases.,How to treat the primary lesion？,Cytoreductive Nephrectomy: Indications: Patients with good performance status, large resectable primary tumor and low metastatic volume, no sarcomatoid tumor.,How to Treat it?,Embolisation of primary tumor:Indications: Patients unfit for surgery, or with non-resectable disease.,How to treat the primary lesion？,How to Treat it?,Metastasectomy:Indications: The decision to resect metastases has to be taken for each site, and on a case-by-case basis; performance status, risk profiles, patient preference and alternative techniques to achieve local control, must be considered.Metastases in lung, pancreas, liver et al could be considered.Metastases in brain or possibly bone may be excluded.,How to deal with the metastases of RCC?,How to Treat it?,Embolization of bone metastases:Indications: Embolization prior to resection; or for relieving symptomsProtocol 1: Embolization prior to resection of hypervascular bone or spinal metastases.Protocol 2: Embolization of bone or paravertebral metastases.,How to deal with the metastases of RCC?,How to Treat it?,Stereotactic Radiotherapy:Indications: Bone and brain metastases.,How to deal with the metastases of RCC?,Systemic therapy for advanced/metastatic RCC,1 Chemotherapy2 Immunotherapy3 Targeted therapies4 Monoclonal antibody against circulating VEGF5 mTOR inhibitors6 Therapeutic strategies and recommendations,1、Chemotherapy,metastatic renal cell carcinoma, mRCC,2、 Immunotherapy,1. IFN- monotherapy and combined with bevacizumab2. Interleukin-23. Vaccines and targeted immunotherapy,Targeted therapies,von Hippel-Lindau (VHL) inactivation,hypoxia-inducible factor (HIF) accumulation,overexpression of vascular endothelial growth factor (VEGF and platelet-derived growth factor(PDGF),neoangiogenesis,This process substantially contributes to the developmentand progression of RCC.,sunitinib,bevacizumab,pazopanib,temsirolimus,everolimus,axitinib,7.4.3 Targeted therapies,Tyrosine kinase inhibitors,sorafenib,sunitinib,pazopanib,axitinib,an oral multikinase inhibitor,an oral tyrosine kinase inhibitor and has antitumour and anti-angiogenic activity,an oral angiogenesis inhibitor,an oral selective second-generation inhibitor of VEGFR-1, -2, and -3.,Monoclonal antibody against circulating VEGF,Bevacizumab monotherapy,bevacizumab + IFN-,IFN-,Bevacizumab is a humanised monoclonal antibody and the combination has higher median FPS than the monontherapy,7.4.4 Monoclonal antibody against circulating VEGF,5、 mTOR inhibitors,Temsirolimus :a specific inhibitor of mTOR .Everolimus: an oral mTOR inhibitor, which is established in the treatment of VEGF-refractory disease.,6、Therapeutic strategies and recommendations,Therapy for treatment-naive patients with clear-cell mRCCSequencing targeted therapyFollowing progression of disease with VEGF-targeted therapy,Treatment after progression of disease with mTOR inhibitionTreatment after progression of disease with cytokinesTreatment after second-line targeted therapyCombination of t