1、GuidelinesonrenalcellcarcinomaEAU-Guidelines-Renal-Cell-Cancer-2015-v2GuidelinesonrenalcellcarcinomaEAU指南解讀之腎細胞癌RCC治療課件1、Introduction2、Treatment of localised RCC3、Treatment of locally advanced RCC4、Treatment of advanced/metastatic RCC5、Systemic therapy for advanced/metastatic RCC1、IntroductionDefini

2、tionRenal 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.DefinitionRenal Cell CarcinomaEpidemiology我國目前研究1 馬建輝等收集了中國大陸19882002年15年間數據較齊全的11個研究單位的資料，19881992、19931997、199

3、82002年3個時間段我國腎和泌尿系統其他惡性腫瘤的發病率分別為4.2610萬、5.4010萬、6.6310萬人口，發病率呈現逐年上升趨勢。我國上海、南京、廣州分別排在第245(4.810萬)、273(3.210萬)、282(2.310萬)。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

4、new cases /year and 12,000 deaths from the disease. 1馬建輝,李嗚,張思維等.中國部分市縣腎癌及泌尿系其他惡性腫瘤發病趨勢比較研究J.中華泌尿外科雜志,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.Epidemiology我國目前研究1 1馬建輝,李Risk factors1 2The most significant r

5、isk 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. 1McLaug

6、hlin 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.Risk factors1 2The most siDiagnosis1.Symptoms Physical examination:Physi

7、cal 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 investigationsGuidelines on Renal Cell Carcinoma. European Association of Urology

8、 2015Diagnosis1.SymptomsGuidelines Diagnosis腎癌的臨床診斷主要依靠影像學檢查；實驗室檢查作為對患者術前一般狀況、肝腎功能以及預后判定的評價指標；確診則需依靠病理學檢查。1推薦必須包括的實驗室檢查項目：尿素氮、肌酐、肝功能、全血細胞計數、血紅蛋白、血鈣、血糖、紅細胞沉降率、堿性磷酸酶和乳酸脫氫酶(推薦分級C)2推薦必須包括的影像學檢查項目：腹部B超或彩色多普勒超聲；胸部X線片(正、側位)、腹部CT平掃和增強掃描(碘過敏試驗陰性、無相關禁忌證者)；腹部CT平掃和增強掃描及胸部X線片是術前臨床分期的主要依據(推薦分級A）3推薦參考選擇的影像學檢查項目：KU

9、B：可為開放性手術選擇手術切口提供幫助核素腎圖或IVU：可用于未行CT增強掃描，無法評價對側腎功能者核素骨顯像：堿性磷酸酶高、有相應骨癥狀或臨床分期期的患者(證據水平I b)胸部CT掃描：胸部x線片有可疑結節、臨床分期期的患者(證據水平I b)頭部MRI、CT掃描：有頭痛或相應神經系統癥狀患者(證據水平T b)腹部MRI掃描：腎功能不全、超聲波檢查或CT檢查提示下腔靜脈瘤栓患者(證據水平I b)。4有條件地區及患者選擇的影像學檢查項目：腎超聲造影、螺旋CT及MRI掃描：主要用于腎癌的診斷和鑒別診斷正電子發射斷層掃描(PET)或PETCT：檢查費用昂貴，主要用于發現遠處轉移病灶以及對化療、細胞因

10、子治療、分子靶向治療或放療的療效評定。腎細胞癌診斷治療指南編寫組.腎細胞癌診斷治療指南(2008年第一版)J.中華泌尿外科雜志,2009,30(1):63-69.Diagnosis腎癌的臨床診斷主要依靠影像學檢查；實驗室檢Guidelines on Renal Cell Carcinoma. European Association of Urology 2015StagingGuidelines on Renal Cell CarciTreatment of localised RCC (T1-2N0M0) For this Guidelines version, an updated se

11、arch was performed up to May 31 st , 2013.Treatment of localised RCC (T1Surgical treatmentAdrenalectomyPartial 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, emboli

12、sation can control symptoms, including gross haematuria or flank painSurgical treatmentAdrenalectomSurgical treatmentConclusions LEPN achieves similar oncological outcomes to RN for clinically localised tumours (cT1). 1b Ipsilateral adrenalectomy during RN or PN has no survival advantage. 3 In patie

13、nts with localised disease without evidence of LN metastases, there is no survival advantage of LND in conjunction with RN. 1b In patients unfit for surgery with massive haematuria or flank pain, embolisation can be a beneficial palliative approach. 3Surgical treatmentConclusions Surgical treatmentR

14、ecommendations GRSurgery is recommended to achieve cure in localised RCC.BPN is recommended in patients with T1a tumours.APN should be favoured over RN in patients with T1b tumour, whenever feasible.BIpsilateral adrenalectomy is not recommended when there is no clinical evidence of invasion of the a

15、drenal gland. B LND is not recommended in localised tumour without clinical evidence of LN invasion. ASurgical treatmentRecommendatiRadical nephrectomyLaparoscopic vs Open RNItemsLaparoscopicOpenPeri-operative blood lossLessmoreAnalgesic requirementLowerHigherHospital stayShorterLongerOperation time

16、ShorterLongerConvalescence timeShorterLongerOncological outcomes*similarsimilarBlood reansfusionSimilarSimilarComplicationsSimilarSimilarPost-operative QoL scoreSimilarsimilar* Need RCTRadical nephrectomyLaparoscopiRadical nephrectomyHand-assisted vs standerd laparoscopic RNItemsHand-assistedstander

17、dOperation timeShorterLongerHospital stayLongerShorterTime to non-strenuous activitiesLongerShorterOSsimilarsimilarCSSsimilarsimilarRFSsimilarsimilarRadical nephrectomyHand-assistPartial nephrectomyLaparoscopic vs Open PNItemsLaparoscopicOpenPeri-operative blood lossLessmoreOperation timeShorterLong

18、erConvalescence timeShorterLongerWarm ischaemia timeShorterLongerGFR declineGreaterLessPFS and OSsimilarsimilarPost-operative mortalitySimilarSimilarComplicationsSimilarSimilarPost-operative QoL scoreSimilarsimilarPartial nephrectomyLaparoscopiConclusion and RecommendationsLaparoscopic RN:Lower morb

19、idity, similar oncological outcomesT1: PNT2 or localised masses not treatable by PN: Laparoscopic RNConclusion and RecommendationsTherapeutic approaches as alternatives to surgeryPopulation-based analyses show a significantly lower cancer-specific mortality for patients treated with surgery compared

20、 to non-surgical management for tumors 75 years).Therapeutic approaches as alteSurveillanceActive 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

21、.Ablative therapiesCryoablation(冷凍消融術)Radiofrequency ablation(射頻消融術)Others：microwave ablation, laser ablation, and high-intensity focused US ablation.SurveillanceRecommendationsRecommendationsGRDue to the low quality of available data no recommendation can be make on RFA and cryoablation.CIn the eld

22、erly and/or comorbid patients with small renal masses and limited life expectancy, active surveillance, RFA and cryoablation can be offered.CRecommendationsRecommendationsTreatment of locally advanced RCCClinically positive lymph nodes (cN+)Locally advanced unresectable RCCRCC with venous thrombusTr

23、eatment of locally advanced Clinically positive lymph nodes (cN+)LND is justifiedBut the extent of LND is controversial Clinically positive lymph nodeLocally advanced unresectable RCCEmbolisation can control symptoms gross haematuria or flank painThe effect of neoadjuvant targeted therapy to downsiz

24、e tumours is unknown.Locally advanced unresectable RCC with venous thrombusTraditionally 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 pr

25、ocedures remain uncertainRCC with venous thrombusTraditAdjuvant therapySeveral 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 followin

26、g surgery.Adjuvant therapySeveral RCTs oTreatment of Advanced/Metastatic Renal Cell CarcinomaTreatment of Advanced/MetastatContentsWhat is Advanced/Metastatic Renal Cell Carcinoma (RCC)?How to Treat it?ContentsWhat is Advanced/MetasWhat is Advanced/Metastatic Renal Cell CarcinomaWhat is Advanced/Met

27、astatic ReHow to Treat it?How to treat the primary lesion？How to deal with the metastases of RCC?How to Treat it?How to treat tHow to Treat it?Protocol 1: Cytoreductive nephrectomy combined with interferon-alpha. Protocol 2: Cytoreductive nephrectomy with simultaneous complete resection of a single

28、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?How to treat tHow to Treat it?Embolisation of primary tumor:Indi

29、cations: Patients unfit for surgery, or with non-resectable disease.How to treat the primary lesion？How to Treat it?Embolisation oHow 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 profile

30、s, 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?MetastasectomyHow to Treat it?Emboli

31、zation 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?

32、Embolization oHow to Treat it?Stereotactic Radiotherapy:Indications: Bone and brain metastases.How to deal with the metastases of RCC?How to Treat it?Stereotactic RSystemic therapy for advanced/metastatic RCC1 Chemotherapy2 Immunotherapy3 Targeted therapies4 Monoclonal antibody against circulating V

33、EGF5 mTOR inhibitors6 Therapeutic strategies and recommendationsSystemic therapy for advanced/1、ChemotherapyConclusionLEIn mRCC 5-FU combined with immunotherapy has equivalent efficacy to IFN-.1bRecommendationGRIn patients with clear-cell mRCC, chemotherapy is not considered effective.Bmetastatic re

34、nal cell carcinoma, mRCC 1、ChemotherapyConclusionLEIn m2、 Immunotherapy1. IFN- monotherapy and combined with bevacizumab2. Interleukin-23. Vaccines and targeted immunotherapy2、 Immunotherapy1. IFN- monotRecommendationGRMonotherapy with IFN-or HD bolus IL-2 is not routinely recommended as first-line

35、therapy in mRCC.ARecommendationGRMonotherapy wiTargeted therapiesvon Hippel-Lindau (VHL) inactivationhypoxia-inducible factor (HIF) accumulationoverexpression of vascular endothelial growth factor (VEGF and platelet-derived growth factor(PDGF)neoangiogenesisThis process substantially contributes to

36、the developmentand progression of RCC.sunitinibbevacizumabpazopanibtemsirolimuseverolimusaxitinib7.4.3 Targeted therapiesTargeted therapiesvon Hippel-LTyrosine kinase inhibitorssorafenibsunitinibpazopanibaxitiniban oral multikinase inhibitoran oral tyrosine kinase inhibitor and has antitumour and an

37、ti-angiogenic activityan oral angiogenesis inhibitoran oral selective second-generation inhibitor of VEGFR-1, -2, and -3.Tyrosine kinase inhibitorssoraMonoclonal antibody against circulating VEGFBevacizumab monotherapybevacizumab + IFN-IFN-Bevacizumab is a humanised monoclonal antibody and the combi

38、nation has higher median FPS than the monontherapy7.4.4 Monoclonal antibody against circulating VEGFMonoclonal antibody against ci5、 mTOR inhibitorsTemsirolimus :a specific inhibitor of mTOR .Everolimus: an oral mTOR inhibitor, which is established in the treatment of VEGF-refractory disease. 5、 mTOR inhibitorsTemsiroli6、Therapeutic strategies and recommendationsTherapy for treatment-naive patients with clear-cell mRCCSequencing targeted therapyFollowing progression of dis