Stein-膀胱癌淋巴清扫资料

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 BLADD

2、ER CANCER 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 CANC

3、ER EXPERIENCERecurrence-Free Survival of 1054 Patients Stratified by Lymph Node Status (LN+ vs. LN-) (6/71-12/97)051015Years from Cystectomy0.000.100.200.300.400.500.600.700.800.901.00Probability of Not RecurringLN + (n=244)LN - (n=810)P0.001第五页，共八十七页。Incidence of Lymph Node Metastases at Cystectomy

4、Author 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 Metastases Following Radical Cystectomy: The Concept of Lymph Node DensityJohn P. Stein, M.D.Uni

5、versity 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, 2001.Radical cystectomy with BPLND24% of patients LN+ diseaseRisk factors include:p-stag

6、e# 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 PatientsJ. Clin. Oncol., 19: 666, 2001.Radical cystectomy with BPLND24% of patients LN+ diseaseRisk factors incl

7、ude:p-stage# 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.Radical cystectomy with BPLND24% of patients LN+ diseaseRisk factors include:p-stage# of LN involved第十一页，共八十七页。USC Radical Cystectomy Experience: Long-Term Result

8、s in 1,054 PatientsJ. Clin. Oncol., 19: 666, 2001.Radical cystectomy with BPLND24% of patients LN+ diseaseRisk factors include:p-stage# of LN involved第十二页，共八十七页。Radical Cystectomy Extent of LymphadenectomyPrognostic factors in LN- disease:Herr et al, J Urol, 167 1298, 2002Poulsen et al, J Urol, 160,

9、 2022, 2002Leissner et al, Br J Urol, 85, 817, 2000第十三页，共八十七页。Radical Cystectomy Extent of LymphadenectomyPrognostic factors in LN- disease:Herr et al, J Urol, 167 1298, 2002Poulsen et al, J Urol, 160, 2022, 2002Leissner et al, Br J Urol, 85, 817, 2000第十四页，共八十七页。Radical Cystectomy Extent of Lymphade

10、nectomyPrognostic factors in LN- disease:Herr et al, J Urol, 167 1298, 2002Poulsen et al, J Urol, 160, 2022, 2002Leissner et al, Br J Urol, 85, 817, 2000第十五页，共八十七页。Radical Cystectomy Extent of LymphadenectomyPrognostic factors in LN- disease:Herr et al, J Urol, 167 1298, 2002Poulsen et al, J Urol, 1

11、60, 2022, 2002Leissner 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 Lymph Node Positive Bladder Cancer ExperiencePurpose1. Evaluate t

12、he 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 Positive Bladder Cancer ExperiencePatientsTime period: July 1971 D

13、ec 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)21 (18)35 (27)112 (45)58 (43)244 (24%)第二十页，共八十七页。Pelvic Iliac Lymphadenectomy第二十一

14、页，共八十七页。Pelvic Iliac LymphadenectomyLevel of the inferior mesenteric artery第二十二页，共八十七页。Genitofemoral nervePelvic Iliac LymphadenectomyLevel of the inferior mesenteric artery第二十三页，共八十七页。Genitofemoral nervePelvic Iliac LymphadenectomyLevel of the inferior mesenteric arteryGenitofemoral nerveLymph node

15、 of Cloquet*第二十四页，共八十七页。Genitofemoral nerveObturator fossaGenitofemoral nervePelvic Iliac LymphadenectomyLymph node of Cloquet*Level of the inferior mesenteric artery第二十五页，共八十七页。Obturator fossaGenitofemoral nervePelvic Iliac LymphadenectomyLevel of the inferior mesenteric arteryLymph node of Cloquet

16、*Presacral 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 Positive Bladder Cancer ExperienceAdjuvant TherapiesChemotherapy139 patients (56%)Postop - 126 (52%)Preop - 7 (3%)Pre & Postop - 6 (2%)Radiation Therapy37 patients (15%)Preop - 26 (11%)Postop - 8 (3%)Pre & Po

17、stop - 3 (1%)第三十页，共八十七页。USC/Norris Lymph Node Positive Bladder Cancer ExperienceLymph NodesMedian # of LN 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 c

18、omplications (27%)No complication directly related to PLND127051015202530%MorbidityMortality第三十二页，共八十七页。USC/Norris Lymph Node Positive Bladder Cancer ExperienceOutcomes AnalysisPresence of CisPrimary pathologic subgroupsTotal # of lymph nodes removedTotal # of lymph nodes involvedLymph node density

19、(# + LN/ # LN removed)第三十三页，共八十七页。USC/Norris Lymph Node Positive Bladder Cancer ExperienceOutcomes AnalysisPresence of CisPrimary 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

20、Overall and Recurrence-Free Survivalfor Patients with LN+ Disease (N = 244)(6/71-12/97)0123456789101112131415Years from Cystectomy0.000.100.200.300.400.500.600.700.800.901.00Probability of SurvivalRecurrence-Free SurvivalOverall Survival第三十五页，共八十七页。USC/ NORRIS BLADDER CANCER EXPERIENCE Recurrence-Fr

21、ee Survival of 244 Patients with LN+ DiseaseStratified 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 EXPERIENCE Recurrence

22、-Free Survival of 244 Patients with LN+ DiseaseStratified by Total Number of Lymph Nodes Removed (15) (6/71-12/97)051015Years from Cystectomy0.000.100.200.300.400.500.600.700.800.901.00Probability 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 Su

23、rvival of 244 Patients with LN+ DiseaseStratified by Pathologic 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 Recur

24、rence-Free Survival of 244 Patients with LN+ DiseaseStratified 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 LN = 8 (n=193)p=0.002第三十九页，共八十七页。USC/ NORRIS BLADDER CANCER EXPER

25、IENCE Recurrence-Free Survival of 244 Patients with LN+ DiseaseStratified by Lymph Node Density (20%)(6/71-12/97)051015Years from Cystectomy0.000.100.200.300.400.500.600.700.800.901.00Probability of Not RecurringLN+ 20% (n=89)LN+ 65 yrs vs. 65 yrs)1.160.37Gender (Female vs. Male)1.270.22Urinary Dive

26、rsion (Continent vs. Conduit)0.760.12Lymph Nodes Removed (15 vs. 65 yrs vs. 65 yrs)1.160.37Gender (Female vs. Male)1.270.22Urinary Diversion (Continent vs. Conduit)0.760.12Lymph Nodes Removed (15 vs. 65 yrs vs. 65 yrs)1.160.37Gender (Female vs. Male)1.270.22Urinary Diversion (Continent vs. Conduit)0

27、.760.12Lymph Nodes Removed (15 vs. 65 yrs vs. 65 yrs)1.160.37Gender (Female vs. Male)1.270.22Urinary Diversion (Continent vs. Conduit)0.760.12Lymph Nodes Removed (15 vs. 20% vs. 20%)2.3665 yrs vs. 65 yrs)1.160.37Gender (Female vs. Male)1.270.22Urinary Diversion (Continent vs. Conduit)0.760.12Lymph N

28、odes Removed (15 vs. 20% vs. 20%)2.368 vs. 8)2.6620% 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

29、of dissection 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, 2002.64 patients with LN+Radical Cyst + PLNDIf 11 LNs removed:Better local control ( 9% vs. 30%)Improved survival (44% vs 20%)051015202530% 11 LNRemovedLocal Recurrence Rate第四十九页，共

30、八十七页。Radical Cystectomy Extent of Lymphadenectomy in LN+ Herr et al., J Urol., 167: 1295, 2002.64 patients with LN+Radical Cyst + PLNDIf 11 LNs removed:Better local control ( 9% vs. 30%)Improved survival (44% vs 20%)第五十页，共八十七页。Radical Cystectomy Extent of Lymphadenectomy in LN+ Herr et al., J Urol.,

31、 167: 1295, 2002.64 patients with LN+Radical Cyst + PLNDIf 11 LNs removed:Better local control ( 9% vs. 30%)Improved survival (44% vs 20%)第五十一页，共八十七页。Radical Cystectomy Outcomes LN+ Disease Herr, J Urol., 169: 943, 2003.162 LN + patientsRadical Cyst + PLNDFollow-up: 7.5 yrs Median LN removed: 13Prog

32、nostic variables:# of LN removed20% LN density第五十二页，共八十七页。Radical Cystectomy Outcomes LN+ Disease Herr, J Urol., 169: 943, 2003.162 LN + patientsRadical Cyst + PLNDFollow-up: 7.5 yrs Median LN removed: 13Prognostic variables:# of LN removed20% LN density第五十三页，共八十七页。Extended Lymphadenectomy: Multicen

33、ter Prospective TrialLeissner et al., J. Urol., 171: 139, 2004.290 cystectomies with extended LNDMapping study81 (28%) LN + dzMedian 43 LN removedCommon site of mets:Obturators-40%Levels:I-below common iliacsII-aortic bifurcation belowIII- IMA to aortic bifurcation第五十四页，共八十七页。Extended Lymphadenectom

34、y: Multicenter Prospective TrialLeissner et al., J. Urol., 171: 139, 2004.Extended dissection takes 60 minutes longerNo increase in morbidity or mortalityFor unilateral bladder tumors- contralateral nodal metastases commonly occurredLymph nodes + at level III only- do not occurLymph nodes + at level

35、 II only in 7%Lymph nodes + at level III occur in 13% and presacral in 6% of all node-positive patients“Strongly 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, 2003.Factors evaluated in the neoadjuvant MVA

36、C trial*270 randomized patients: 24 no LND98 limited LND146 standard LNDMedian # of LN removed: 10 LNsSurvival:44% if 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 IN BLADDER CANCERHerr H., BJU, 92: 187, 2003.Significant Factors in Multivariate AnalysisExtent

37、 of the node dissectionNumber of lymph nodes removed# of cases performed by the operating surgeon“Surgical factors and not chemotherapy were the most important predictors of outcome in this randomized trial!第五十七页，共八十七页。USC Lymph Node Positive Bladder Cancer Experience Prognostic VariablesPathologic

38、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 Bladder Cancer ConclusionsExtended lymphadenectomy is an important component in the treatment of high-grade, invas

39、ive 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 Node Positive Bladder Cancer ConclusionsLymph node density is a novel concept and prognostic indicator.Lymph node d

40、ensity 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 Positive Bladder Cancer Extended LymphadenectomyBetter risk assessment for LN+ patients:pathologic subgroup (p-stage)#

41、of lymph nodes removed # of lymph nodes involved with tumorlymph node densityAdjuvant chemotherapy:based on risk assessmentclinical trials第六十一页，共八十七页。第六十二页，共八十七页。USC BLADDER CANCER EXPERIENCE RADICAL CYSTECTOMY ConclusionsBest survival resultsLow local (pelvic) recurrence (7%)Lowest incidence of dev

42、eloping metastatic or progressive disease (29%)第六十三页，共八十七页。USC BLADDER CANCER EXPERIENCE RADICAL CYSTECTOMY ConclusionsImproved morbidity and mortalityUrinary reconstructive options available and improvingEqually effective therapies have not emerged第六十四页，共八十七页。USC BLADDER CANCER EXPERIENCE “Radical

43、cystectomy remains the preferred form of definitive therapy for invasive bladder cancer.第六十五页，共八十七页。Donald G. Skinner第六十六页，共八十七页。USC BLADDER CANCER EXPERIENCE Reality“There is a significant error in clinical staging of invasive bladder cancer.第六十七页，共八十七页。PRIMARY TREATMENT GOALS OF MUSCLE INVASIVE BL

44、ADDER CANCERPatient survivalPrevent consequences of pelvic progression/recurrencePrevent consequences of metastatic disease第六十八页，共八十七页。USC BLADDER CANCER EXPERIENCE Complications by Adjuvant Therapy第六十九页，共八十七页。BLADDER CANCER: INDICATIONS FOR RADICAL CYSTECTOMYMuscle invasive tumor第七十页，共八十七页。BLADDER

45、CANCER: INDICATIONS FOR RADICAL CYSTECTOMYMuscle invasive tumorHigh grade tumor with cis第七十一页，共八十七页。BLADDER CANCER: INDICATIONS FOR RADICAL CYSTECTOMYMuscle invasive tumorHigh grade tumor with ciscis unresponsive to intravesical therapy第七十二页，共八十七页。BLADDER CANCER: INDICATIONS FOR RADICAL CYSTECTOMYMu

46、scle invasive tumorHigh grade tumor with ciscis unresponsive to intravesical therapyRecurrent multifocal high grade tumors unresponsive to intravesical therapy第七十三页，共八十七页。BLADDER CANCER: INDICATIONS FOR RADICAL CYSTECTOMYMuscle invasive tumorHigh grade tumor with ciscis unresponsive to intravesical

47、therapyRecurrent multifocal high grade tumors unresponsive to intravesical therapyEndoscopically uncontrollable tumors第七十四页，共八十七页。BLADDER CANCER: INDICATIONS FOR RADICAL CYSTECTOMYMuscle invasive tumorHigh grade tumor with ciscis unresponsive to intravesical therapyRecurrent multifocal high grade tumors unresponsive to intravesical therapyEndoscopically uncontrollable tumorsTumors associated with a diverticulum第七十五页，共八十七页。第七十六页，共八十七页。USC/NORRIS BLADDER CANCER EXPERIENCE Overall and Recurrence-Free Survivalfor Patients wit