医学专题一Stein-膀胱癌淋巴清扫资料.ppt

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1、The Role of Lymphadenectomy in Bladder CancerJohn P.Stein,M.D.University of Southern California Keck School of Medicine,Norris Comprehensive Cancer Center,Los Angeles CA第一页，共八十七页。第二页，共八十七页。HIGH-GRADE,INVASIVE BLADDER CANCER Reality“Invasive bladder cancer is a lethal disease.”第三页，共八十七页。USC BLADDER C

2、ANCER EXPERIENCE Rationale for CystectomyBest survival resultsLowest local recurrence ratesImproved morbidity and mortalityUrinary reconstruction has improved quality of life(continent and orthotopic diversion)Equally effective forms of therapy have not emerged第四页，共八十七页。USC/NORRIS BLADDER CANCER EXP

3、ERIENCEUSC/NORRIS BLADDER CANCER EXPERIENCERecurrence-Free Survival of 1054 Patients Recurrence-Free Survival of 1054 Patients Stratified by Lymph Node Status (LN+vs.LN-)Stratified by Lymph Node Status (LN+vs.LN-)(6/71-12/97)051015Years from Cystectomy0.000.100.200.300.400.500.600.700.800.901.00Prob

4、ability of Not RecurringLN+(n=244)LN-(n=810)P0.001第五页，共八十七页。Incidence of Lymph Node Metastases at CystectomyAuthor Years Total#Pts LN+Poulsen 90-97191 50(26%)Vieweg 80-90686 193(28%)Leissner 99-02290 81(28%)Stein 71-97 1054 246(24%)Totals 2221 570(25%)第六页，共八十七页。第七页，共八十七页。Risk Factors for Lymph Node

5、Metastases Following Radical Cystectomy:The Concept of Lymph Node DensityJohn P.Stein,M.D.University of Southern California Keck School of Medicine,Norris Comprehensive Cancer Center,Los Angeles CA第八页，共八十七页。USC Radical Cystectomy Experience:Long-Term Results in 1,054 PatientsJ.Clin.Oncol.,19:666,200

6、1.J.Clin.Oncol.,19:666,2001.Radical cystectomy with BPLND24%of patients LN+diseaseRisk factors include:n np-stagen n#of LN involved第九页，共八十七页。Organ Confined(n=594)Extravesical(n=214)Lymph Node(+)(n=246)P 0.001Probability of Not RecurringUSC Radical Cystectomy Experience:Long-Term Results in 1,054 Pat

7、ientsJ.Clin.Oncol.,19:666,2001.J.Clin.Oncol.,19:666,2001.Radical cystectomy with BPLND24%of patients LN+diseaseRisk factors include:n np-stagen n#of LN involved第十页，共八十七页。USC Radical Cystectomy Experience:Long-Term Results in 1,054 PatientsJ.Clin.Oncol.,19:666,2001.J.Clin.Oncol.,19:666,2001.Radical c

8、ystectomy with BPLND24%of patients LN+diseaseRisk factors include:n np-stagen n#of LN involved第十一页，共八十七页。USC Radical Cystectomy Experience:Long-Term Results in 1,054 PatientsJ.Clin.Oncol.,19:666,2001.J.Clin.Oncol.,19:666,2001.Radical cystectomy with BPLND24%of patients LN+diseaseRisk factors include

9、:n np-stagen n#of LN involved第十二页，共八十七页。Radical Cystectomy Extent of LymphadenectomyPrognostic factors in LN-disease:n nHerr et al,J Urol,167 Herr et al,J Urol,167 1298,20021298,2002n nPoulsen et al,J Urol,160,Poulsen et al,J Urol,160,2015,20022015,2002n nLeissner et al,Br J Urol,Leissner et al,Br J

10、 Urol,85,817,200085,817,2000第十三页，共八十七页。Radical Cystectomy Extent of LymphadenectomyPrognostic factors in LN-disease:n nHerr et al,J Urol,167 Herr et al,J Urol,167 1298,20021298,2002n nPoulsen et al,J Urol,160,2015,2002n nLeissner et al,Br J Urol,Leissner et al,Br J Urol,85,817,200085,817,2000第十四页，共八

11、十七页。Radical Cystectomy Extent of LymphadenectomyPrognostic factors in LN-disease:n nHerr et al,J Urol,167 1298,2002n nPoulsen et al,J Urol,160,2015,2002n nLeissner et al,Br J Urol,Leissner et al,Br J Urol,85,817,200085,817,2000第十五页，共八十七页。Radical Cystectomy Extent of LymphadenectomyPrognostic factors

12、 in LN-disease:n nHerr et al,J Urol,167 1298,2002n nPoulsen et al,J Urol,160,2015,2002n nLeissner et al,Br J Urol,85,817,2000第十六页，共八十七页。Lymph Node Positive Bladder Cancer Lymph Node DensityNovel concept#of involved LN/#of LN removedAccounts for:1.LN tumor burden2.Extent of PLND第十七页，共八十七页。USC/Norris

13、Lymph Node Positive Bladder Cancer ExperiencePurpose1.Evaluate the clinical outcomes and risk factors for patients with lymph node metastases following radical cystectomy.2.Evaluate the concept of lymph node density(#positive lymph nodes/#lymph nodes removed).第十八页，共八十七页。USC/Norris Lymph Node Positiv

14、e Bladder Cancer ExperiencePatientsTime period:July 1971 Dec 1997Total lymph node+:244(24%)Gender:191 males(78%);53 females Age:median 66 years(range 36-90)Follow-up:median 10.1 years(range 0-26)第十九页，共八十七页。USC BLADDER CANCER EXPERIENCE P-Stage and Lymph Node+19(5)19(5)21(18)21(18)35(27)35(27)112(45)

15、112(45)58(43)58(43)244 244 (24%)(24%)第二十页，共八十七页。Pelvic Iliac Lymphadenectomy第二十一页，共八十七页。Pelvic Iliac LymphadenectomyLevel of the inferior mesenteric arteryLevel of the inferior mesenteric artery第二十二页，共八十七页。Genitofemoral nerveGenitofemoral nervePelvic Iliac LymphadenectomyLevel of the inferior mesent

16、eric arteryLevel of the inferior mesenteric artery第二十三页，共八十七页。Genitofemoral nerveGenitofemoral nervePelvic Iliac LymphadenectomyLevel of the inferior mesenteric arteryLevel of the inferior mesenteric arteryGenitofemoral nerveGenitofemoral nerveLymph node of CloquetLymph node of Cloquet*第二十四页，共八十七页。G

17、enitofemoral nerveGenitofemoral nerveObturator fossaObturator fossaGenitofemoral nerveGenitofemoral nervePelvic Iliac LymphadenectomyLymph node of CloquetLymph node of Cloquet*Level of the inferior mesenteric arteryLevel of the inferior mesenteric artery第二十五页，共八十七页。Obturator fossaObturator fossaGeni

18、tofemoral nerveGenitofemoral nervePelvic Iliac LymphadenectomyLevel of the inferior mesenteric arteryLevel of the inferior mesenteric arteryLymph node of CloquetLymph node of Cloquet*Presacral lymph nodesPresacral lymph nodes第二十六页，共八十七页。第二十七页，共八十七页。第二十八页，共八十七页。第二十九页，共八十七页。USC/Norris Lymph Node Posit

19、ive Bladder Cancer ExperienceAdjuvant TherapiesChemotherapy139 patients(56%)n nPostop-126(52%)n nPreop-7(3%)n nPre&Postop-6(2%)Radiation Therapy37 patients(15%)n nPreop-26(11%)n nPostop-8(3%)n nPre&Postop-3(1%)第三十页，共八十七页。USC/Norris Lymph Node Positive Bladder Cancer ExperienceLymph NodesMedian#of LN

20、 removed:30(range 1-96)Median#of LN involved:2 (range 1-63)302第三十一页，共八十七页。USC/Norris Lymph Node Positive Bladder Cancer ExperienceMorbidity and Mortality2 perioperative deaths(1%)66 early complications(27%)No complication directly related to PLND127051015202530%MorbidityMortality第三十二页，共八十七页。USC/Norr

21、is Lymph Node Positive Bladder Cancer ExperienceOutcomes AnalysisPresence of CisPrimary pathologic subgroupsTotal#of lymph nodes removedTotal#of lymph nodes involvedLymph node density(#+LN/#LN removed)第三十三页，共八十七页。USC/Norris Lymph Node Positive Bladder Cancer ExperienceOutcomes AnalysisPresence of Ci

22、sPrimary pathologic subgroupTotal#of lymph nodes removedTotal#of lymph nodes involvedLymph node density(#+LN/#LN removed)第三十四页，共八十七页。USC/NORRIS BLADDER CANCER EXPERIENCE Overall and Recurrence-Free Survivalfor Patients with LN+Disease(N=244)(6/71-12/97)0123456789101112131415Years from Cystectomy0.00

23、0.100.200.300.400.500.600.700.800.901.00Probability of SurvivalRecurrence-Free SurvivalOverall Survival第三十五页，共八十七页。USC/NORRIS BLADDER CANCER EXPERIENCEUSC/NORRIS BLADDER CANCER EXPERIENCE Recurrence-Free Survival of 244 Patients with LN+DiseaseRecurrence-Free Survival of 244 Patients with LN+Disease

24、Stratified by Carcinoma in Situ (Present/Absent)Stratified by Carcinoma in Situ (Present/Absent)(6/71-12/97)051015Years from Cystectomy0.000.100.200.300.400.500.600.700.800.901.00Probability of Not RecurringAbsent (n=91)Present(n=153)p=0.73第三十六页，共八十七页。USC/NORRIS BLADDER CANCER EXPERIENCEUSC/NORRIS B

25、LADDER CANCER EXPERIENCE Recurrence-Free Survival of 244 Patients with LN+DiseaseRecurrence-Free Survival of 244 Patients with LN+DiseaseStratified by Total Number of Lymph Nodes Removed Stratified by Total Number of Lymph Nodes Removed(15)(15)(6/71-12/97)051015Years from Cystectomy0.000.100.200.300

26、.400.500.600.700.800.901.00Probability of Not RecurringLN 15(n=209)p=0.21第三十七页，共八十七页。USC/NORRIS BLADDER CANCER EXPERIENCE Recurrence-Free Survival of 244 Patients with LN+DiseaseRecurrence-Free Survival of 244 Patients with LN+DiseaseStratified by Pathologic Subgroups(OC vs.EV)Stratified by Patholog

27、ic Subgroups(OC vs.EV)(6/71-12/97)051015Years from Cystectomy0.000.100.200.300.400.500.600.700.800.901.00Probability of Not RecurringExtravesical (n=169)Organ Confined(n=75)p=0.003第三十八页，共八十七页。USC/NORRIS BLADDER CANCER EXPERIENCE USC/NORRIS BLADDER CANCER EXPERIENCE Recurrence-Free Survival of 244 Pa

28、tients with LN+DiseaseRecurrence-Free Survival of 244 Patients with LN+DiseaseStratified by Number of Positive Nodes (8)Stratified by Number of Positive Nodes (8)(6/71-12/97)051015Years from Cystectomy0.000.100.200.300.400.500.600.700.800.901.00Probability of Not RecurringPositive LN 8(n=51)Positive

29、 LN=8(n=193)p=0.002第三十九页，共八十七页。USC/NORRIS BLADDER CANCER EXPERIENCE Recurrence-Free Survival of 244 Patients with LN+DiseaseRecurrence-Free Survival of 244 Patients with LN+DiseaseStratified by Lymph Node Density Stratified by Lymph Node Density (20%)(20%)(6/71-12/97)051015Years from Cystectomy0.000

30、.100.200.300.400.500.600.700.800.901.00Probability of Not RecurringLN+20%(n=89)LN+65 yrs vs.65 yrs)Age(65 yrs vs.65 yrs)1.161.160.370.37Gender(Female vs.Male)Gender(Female vs.Male)1.271.270.220.22Urinary Diversion(Continent vs.Conduit)Urinary Diversion(Continent vs.Conduit)0.760.760.120.12Lymph Node

31、s Removed(15 vs.15)Lymph Nodes Removed(15 vs.65 yrs vs.65 yrs)Age(65 yrs vs.65 yrs)1.161.160.370.37Gender(Female vs.Male)Gender(Female vs.Male)1.271.270.220.22Urinary Diversion(Continent vs.Conduit)Urinary Diversion(Continent vs.Conduit)0.760.760.120.12Lymph Nodes Removed(15 vs.15)Lymph Nodes Remove

32、d(15 vs.65 yrs vs.65 yrs)Age(65 yrs vs.65 yrs)1.161.160.370.37Gender(Female vs.Male)Gender(Female vs.Male)1.271.270.220.22Urinary Diversion(Continent vs.Conduit)Urinary Diversion(Continent vs.Conduit)0.760.760.120.12Lymph Nodes Removed(15 vs.15)Lymph Nodes Removed(15 vs.65 yrs vs.65 yrs)Age(65 yrs v

33、s.65 yrs)1.161.160.370.37Gender(Female vs.Male)Gender(Female vs.Male)1.271.270.220.22Urinary Diversion(Continent vs.Conduit)Urinary Diversion(Continent vs.Conduit)0.760.760.120.12Lymph Nodes Removed(15 vs.15)Lymph Nodes Removed(15 vs.20%vs.20%)Lymph Node Density(20%vs.20%)2.362.360.00165 yrs vs.65 y

34、rs)Age(65 yrs vs.65 yrs)1.161.160.370.37Gender(Female vs.Male)Gender(Female vs.Male)1.271.270.220.22Urinary Diversion(Continent vs.Conduit)Urinary Diversion(Continent vs.Conduit)0.760.760.120.12Lymph Nodes Removed(15 vs.15)Lymph Nodes Removed(15 vs.20%vs.20%)Lymph Node Density(20%vs.20%)2.362.360.00

35、18 vs.8)Lymph Nodes Involved(8 vs.8)2.662.660.00120%vs.20%)Lymph Nodes Involved 1.910.008(8 vs.8)第四十七页，共八十七页。Radical Cystectomy for High Grade Invasive Bladder CancerLymphadenectomy1.Allows for a safe anatomical dissection 2.Provides pathologic staging3.Therapeutic benefits4.Absolute limits of disse

36、ction unknown?第四十八页，共八十七页。Radical Cystectomy Extent of Lymphadenectomy in LN+Herr et al.,J Urol.,167:1295,2002.Herr et al.,J Urol.,167:1295,2002.64 patients with LN+Radical Cyst+PLNDIf 11 LNs removed:n nBetter local control (9%vs.30%)n nImproved survival (44%vs 20%)051015202530%11 LNRemovedLocal Rec

37、urrence Rate第四十九页，共八十七页。Radical Cystectomy Extent of Lymphadenectomy in LN+Herr et al.,J Urol.,167:1295,2002.Herr et al.,J Urol.,167:1295,2002.64 patients with LN+Radical Cyst+PLNDIf 11 LNs removed:n nBetter local control (9%vs.30%)n nImproved survival (44%vs 20%)第五十页，共八十七页。Radical Cystectomy Extent

38、 of Lymphadenectomy in LN+Herr et al.,J Urol.,167:1295,2002.Herr et al.,J Urol.,167:1295,2002.64 patients with LN+Radical Cyst+PLNDIf 11 LNs removed:n nBetter local control (9%vs.30%)n nImproved survival (44%vs 20%)第五十一页，共八十七页。Radical Cystectomy Outcomes LN+Disease Herr,J Urol.,169:943,2003.Herr,J U

39、rol.,169:943,2003.162 LN+patientsRadical Cyst+PLNDFollow-up:7.5 yrs Median LN removed:13Prognostic variables:n n#of LN removed#of LN removedn n20%LN density20%LN density第五十二页，共八十七页。Radical Cystectomy Outcomes LN+Disease Herr,J Urol.,169:943,2003.Herr,J Urol.,169:943,2003.162 LN+patientsRadical Cyst+

40、PLNDFollow-up:7.5 yrs Median LN removed:13Prognostic variables:n n#of LN removed#of LN removedn n20%LN density20%LN density第五十三页，共八十七页。Extended Lymphadenectomy:Multicenter Prospective TrialLeissner et al.,J.Urol.,171:139,2004.Leissner et al.,J.Urol.,171:139,2004.290 cystectomies with extended 290 cy

41、stectomies with extended LNDLND Mapping studyMapping study 81(28%)LN+dz81(28%)LN+dz Median 43 LN removedMedian 43 LN removed Common site of mets:Common site of mets:n nObturators-40%Obturators-40%Levels:Levels:n nI-below common iliacsI-below common iliacsn nII-aortic bifurcation belowII-aortic bifur

42、cation belown nIII-IMA to aortic bifurcationIII-IMA to aortic bifurcation第五十四页，共八十七页。Extended Lymphadenectomy:Multicenter Prospective TrialLeissner et al.,J.Urol.,171:139,2004.Leissner et al.,J.Urol.,171:139,2004.Extended dissection takes 60 minutes longerExtended dissection takes 60 minutes longerN

43、o increase in morbidity or mortalityFor unilateral bladder tumors-contralateral nodal metastases commonly occurredLymph nodes+at level III only-only-do not occur do not occurLymph nodes+at level II only in 7%Lymph nodes+at level III occur in 13%and presacral in 6%of all node-positive patients“Strong

44、ly recommend an extended bilateral LND in all patients undergoing cystectomy”第五十五页，共八十七页。SURGICAL FACTORS IN BLADDER CANCERHerr H.,BJU,92:187,2003Herr H.,BJU,92:187,2003.Factors evaluated in the Factors evaluated in the neoadjuvant MVAC trialneoadjuvant MVAC trial*270 randomized patients:270 randomi

45、zed patients:n n24 no LND24 no LNDn n98 limited LND98 limited LNDn n146 standard LND146 standard LND Median#of LN removed:10 Median#of LN removed:10 LNsLNs Survival:Survival:n n44%if 10 LN removed44%if 10 LN removed 10 LN removed*Grossman et al,N Eng J Med,349:859,2003.第五十六页，共八十七页。SURGICAL FACTORS I

46、N BLADDER CANCERHerr H.,BJU,92:187,2003.Herr H.,BJU,92:187,2003.Significant Factors in Multivariate Analysis1.Extent of the node dissection2.Number of lymph nodes removed3.#of cases performed by the operating surgeon“Surgical factors and not chemotherapy were the most important predictors of outcome

47、 in this randomized trial!”第五十七页，共八十七页。USC Lymph Node Positive Bladder Cancer Experience Prognostic VariablesPathologic subgroups(primary tumor)Administration of adjuvant chemotherapyTotal#of lymph nodes involved with tumorTotal#of lymph nodes removedLymph node density第五十八页，共八十七页。Lymph Node Positive

48、 Bladder Cancer ConclusionsExtended lymphadenectomy is an important component in the treatment of high-grade,invasive bladder cancer.Long-term survival in over 30%of patients with lymph node positive disease.Certain prognostic variables stratify this high-risk group of patients.第五十九页，共八十七页。Lymph Nod

49、e Positive Bladder Cancer ConclusionsLymph node density is a novel concept and prognostic indicator.Lymph node density relates the lymph node tumor burden and the number of lymph nodes removed.Future clinical trials and staging systems should consider lymph node density.第六十页，共八十七页。Lymph Node Positiv

50、e Bladder Cancer Extended LymphadenectomyBetter risk assessment for LN+patients:n npathologic subgroup(p-stage)n n#of lymph nodes removed n n#of lymph nodes involved with tumorn nlymph node densityAdjuvant chemotherapy:n nbased on risk assessmentn nclinical trials第六十一页，共八十七页。第六十二页，共八十七页。USC BLADDER