Stein-膀胱癌淋巴清扫资料.ppt

1、The Role of Lymphadenectomy in Bladder Cancer,John P. Stein, M.D. University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles CA,HIGH-GRADE, INVASIVE BLADDER CANCER Reality,“Invasive bladder cancer is a lethal disease.”,USC BLADDER CANCER EXPERIENCE Rat

2、ionale for Cystectomy,Best survival results Lowest local recurrence rates Improved morbidity and mortality Urinary reconstruction has improved quality of life (continent and orthotopic diversion) Equally effective forms of therapy have not emerged,USC/ NORRIS BLADDER CANCER EXPERIENCERecurrence-Free

3、 Survival of 1054 Patients Stratified by Lymph Node Status (LN+ vs. LN-),(6/71-12/97),0,5,10,15,Years from Cystectomy,0.00,0.10,0.20,0.30,0.40,0.50,0.60,0.70,0.80,0.90,1.00,Probability of Not Recurring,LN + (n=244),LN - (n=810),P0.001,Incidence of Lymph Node Metastases at Cystectomy,Author Years Tot

4、al # 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%),Risk Factors for Lymph Node Metastases Following Radical Cystectomy: The Concept of Lymph Node Density,John P. Stein, M.D. University of Southern California Ke

5、ck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles CA,USC Radical Cystectomy Experience: Long-Term Results in 1,054 PatientsJ. Clin. Oncol., 19: 666, 2001.,Radical cystectomy with BPLND 24% of patients LN+ disease Risk factors include: p-stage # of LN involved,USC Radical Cystect

6、omy Experience: Long-Term Results in 1,054 PatientsJ. Clin. Oncol., 19: 666, 2001.,Radical cystectomy with BPLND 24% of patients LN+ disease Risk factors include: p-stage # of LN involved,USC Radical Cystectomy Experience: Long-Term Results in 1,054 PatientsJ. Clin. Oncol., 19: 666, 2001.,Radical cy

7、stectomy with BPLND 24% of patients LN+ disease Risk factors include: p-stage # of LN involved,USC Radical Cystectomy Experience: Long-Term Results in 1,054 PatientsJ. Clin. Oncol., 19: 666, 2001.,Radical cystectomy with BPLND 24% of patients LN+ disease Risk factors include: p-stage # of LN involve

8、d,Radical Cystectomy Extent of Lymphadenectomy,Prognostic factors in LN- disease: Herr et al, J Urol, 167 1298, 2002 Poulsen et al, J Urol, 160, 2015, 2002 Leissner et al, Br J Urol, 85, 817, 2000,Radical Cystectomy Extent of Lymphadenectomy,Prognostic factors in LN- disease: Herr et al, J Urol, 167

9、 1298, 2002 Poulsen et al, J Urol, 160, 2015, 2002 Leissner et al, Br J Urol, 85, 817, 2000,Radical Cystectomy Extent of Lymphadenectomy,Prognostic factors in LN- disease: Herr et al, J Urol, 167 1298, 2002 Poulsen et al, J Urol, 160, 2015, 2002 Leissner et al, Br J Urol, 85, 817, 2000,Radical Cyste

10、ctomy Extent of Lymphadenectomy,Prognostic factors in LN- disease: Herr et al, J Urol, 167 1298, 2002 Poulsen et al, J Urol, 160, 2015, 2002 Leissner et al, Br J Urol, 85, 817, 2000,Lymph Node Positive Bladder Cancer Lymph Node Density,Novel concept # of involved LN / # of LN removed Accounts for: 1

11、. LN tumor burden 2. Extent of PLND,USC/Norris Lymph Node Positive Bladder Cancer ExperiencePurpose,1. 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

12、nodes removed).,USC/Norris Lymph Node Positive Bladder Cancer ExperiencePatients,Time period: July 1971 Dec 1997 Total 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),USC BLADDER CANCER EXPERIENCE P-Stage and Ly

13、mph Node +,Pelvic Iliac Lymphadenectomy,Pelvic Iliac Lymphadenectomy,Pelvic Iliac Lymphadenectomy,Pelvic Iliac Lymphadenectomy,Obturator fossa,Pelvic Iliac Lymphadenectomy,Level of the inferior mesenteric artery,Obturator fossa,Pelvic Iliac Lymphadenectomy,Presacral lymph nodes,USC/Norris Lymph Node

14、 Positive Bladder Cancer ExperienceAdjuvant Therapies,Chemotherapy 139 patients (56%) Postop - 126 (52%) Preop - 7 (3%) Pre & Postop - 6 (2%),Radiation Therapy 37 patients (15%) Preop - 26 (11%) Postop - 8 (3%) Pre & Postop - 3 (1%),USC/Norris Lymph Node Positive Bladder Cancer ExperienceLymph Nodes

15、,Median # of LN removed: 30 (range 1-96) Median # of LN involved: 2 (range 1-63),30,2,USC/Norris Lymph Node Positive Bladder Cancer ExperienceMorbidity and Mortality,2 perioperative deaths (1%) 66 early complications (27%) No complication directly related to PLND,1,27,0,5,10,15,20,25,30,%,Morbidity,

16、Mortality,USC/Norris Lymph Node Positive Bladder Cancer ExperienceOutcomes Analysis,Presence of Cis Primary pathologic subgroups Total # of lymph nodes removed Total # of lymph nodes involved Lymph node density (# + LN/ # LN removed),USC/Norris Lymph Node Positive Bladder Cancer ExperienceOutcomes A

17、nalysis,Presence of Cis Primary pathologic subgroup Total # of lymph nodes removed Total # of lymph nodes involved Lymph node density (# + LN/ # LN removed),USC/NORRIS BLADDER CANCER EXPERIENCE Overall and Recurrence-Free Survivalfor Patients with LN+ Disease (N = 244),(6/71-12/97),0,1,2,3,4,5,6,7,8

18、,9,10,11,12,13,14,15,Years from Cystectomy,0.00,0.10,0.20,0.30,0.40,0.50,0.60,0.70,0.80,0.90,1.00,Probability of Survival,Recurrence-Free Survival,Overall Survival,USC/ NORRIS BLADDER CANCER EXPERIENCE Recurrence-Free Survival of 244 Patients with LN+ DiseaseStratified by Carcinoma in Situ (Present

19、/ Absent),(6/71-12/97),0,5,10,15,Years from Cystectomy,0.00,0.10,0.20,0.30,0.40,0.50,0.60,0.70,0.80,0.90,1.00,Probability of Not Recurring,Absent (n=91),Present (n=153),p=0.73,USC/ NORRIS BLADDER CANCER EXPERIENCE Recurrence-Free Survival of 244 Patients with LN+ DiseaseStratified by Total Number of

20、 Lymph Nodes Removed (15),(6/71-12/97),0,5,10,15,Years from Cystectomy,0.00,0.10,0.20,0.30,0.40,0.50,0.60,0.70,0.80,0.90,1.00,Probability of Not Recurring,LN =15 (n=35),LN 15 (n=209),p=0.21,USC/ NORRIS BLADDER CANCER EXPERIENCE Recurrence-Free Survival of 244 Patients with LN+ DiseaseStratified by P

21、athologic Subgroups (OC vs. EV),(6/71-12/97),0,5,10,15,Years from Cystectomy,0.00,0.10,0.20,0.30,0.40,0.50,0.60,0.70,0.80,0.90,1.00,Probability of Not Recurring,Extravesical (n=169),Organ Confined (n=75),p=0.003,USC/ NORRIS BLADDER CANCER EXPERIENCE Recurrence-Free Survival of 244 Patients with LN+

22、DiseaseStratified by Number of Positive Nodes (8),(6/71-12/97),0,5,10,15,Years from Cystectomy,0.00,0.10,0.20,0.30,0.40,0.50,0.60,0.70,0.80,0.90,1.00,Probability of Not Recurring,Positive LN 8 (n=51),Positive LN = 8 (n=193),p=0.002,USC/ NORRIS BLADDER CANCER EXPERIENCE Recurrence-Free Survival of 24

23、4 Patients with LN+ DiseaseStratified by Lymph Node Density (20%),(6/71-12/97),0,5,10,15,Years from Cystectomy,0.00,0.10,0.20,0.30,0.40,0.50,0.60,0.70,0.80,0.90,1.00,Probability of Not Recurring,LN+ 20% (n=89),LN+ =20% (n=155),p=0.001,USC/ NORRIS BLADDER CANCER EXPERIENCE Recurrence-Free Survival of

24、 244 Patients with LN+ DiseaseStratified by Adjuvant Chemotherapy (Yes vs. No),(6/71-12/97),0,5,10,15,Years from Cystectomy,0.00,0.10,0.20,0.30,0.40,0.50,0.60,0.70,0.80,0.90,1.00,Probability of Not Recurring,No (n=105),Yes (n=139),p=0.036,Prognostic Factors in LN(+) Bladder Ca Univariate Analysis,Re

25、currence-Free Survival Prognostic FactorsRRp-Value Age (65 yrs vs. 65 yrs)1.160.37 Gender (Female vs. Male)1.270.22 Urinary Diversion (Continent vs. Conduit)0.760.12 Lymph Nodes Removed (15 vs. 15)0.730.21,Prognostic Factors in LN(+) Bladder Ca Univariate Analysis,Recurrence-Free Survival Prognostic

26、 FactorsRRp-Value Age (65 yrs vs. 65 yrs)1.160.37 Gender (Female vs. Male)1.270.22 Urinary Diversion (Continent vs. Conduit)0.760.12 Lymph Nodes Removed (15 vs. 15)0.730.21 Adjuvant Chemotherapy (Yes vs. No)0.700.038,Prognostic Factors in LN(+) Bladder Ca Univariate Analysis,Recurrence-Free Survival

27、 Prognostic FactorsRRp-Value Age (65 yrs vs. 65 yrs)1.160.37 Gender (Female vs. Male)1.270.22 Urinary Diversion (Continent vs. Conduit)0.760.12 Lymph Nodes Removed (15 vs. 15)0.730.21 Adjuvant Chemotherapy (Yes vs. No)0.700.038 Pathologic Subgroup (EV vs. OC)1.720.004,Prognostic Factors in LN(+) Bla

28、dder Ca Univariate Analysis,Recurrence-Free Survival Prognostic FactorsRRp-Value Age (65 yrs vs. 65 yrs)1.160.37 Gender (Female vs. Male)1.270.22 Urinary Diversion (Continent vs. Conduit)0.760.12 Lymph Nodes Removed (15 vs. 20% vs. 20%)2.360.001,Prognostic Factors in LN(+) Bladder Ca Univariate Anal

29、ysis,Recurrence-Free Survival Prognostic FactorsRRp-Value Age (65 yrs vs. 65 yrs)1.160.37 Gender (Female vs. Male)1.270.22 Urinary Diversion (Continent vs. Conduit)0.760.12 Lymph Nodes Removed (15 vs. 20% vs. 20%)2.368 vs. 8)2.660.001,Prognostic Factors in LN(+) Bladder Ca Multivariable Analysis,Rec

30、urrence-Free Survival Prognostic FactorsRRp-Value Pathologic Subgroup 1.460.05 (EV vs. OC) Adjuvant Chemotherapy 0.630.008 (Yes vs. No) Lymph Node Density 1.650.02 (20% vs. 20%) Lymph Nodes Involved 1.910.008 (8 vs. 8),Radical Cystectomy for High Grade Invasive Bladder CancerLymphadenectomy,1. Allow

31、s for a safe anatomical dissection 2. Provides pathologic staging 3. Therapeutic benefits 4. Absolute limits of dissection unknown ?,Radical Cystectomy Extent of Lymphadenectomy in LN+ Herr et al., J Urol., 167: 1295, 2002.,64 patients with LN+ Radical Cyst + PLND If 11 LNs removed: Better local con

32、trol ( 9% vs. 30%) Improved survival (44% vs 20%),0,5,10,15,20,25,30,%, 11 LN,Removed, 11 LN,Removed,Local Recurrence Rate,Radical Cystectomy Extent of Lymphadenectomy in LN+ Herr et al., J Urol., 167: 1295, 2002.,64 patients with LN+ Radical Cyst + PLND If 11 LNs removed: Better local control ( 9%

33、vs. 30%) Improved survival (44% vs 20%),Radical Cystectomy Extent of Lymphadenectomy in LN+ Herr et al., J Urol., 167: 1295, 2002.,64 patients with LN+ Radical Cyst + PLND If 11 LNs removed: Better local control ( 9% vs. 30%) Improved survival (44% vs 20%),Radical Cystectomy Outcomes LN+ Disease Her

34、r, J Urol., 169: 943, 2003.,162 LN + patients Radical Cyst + PLND Follow-up: 7.5 yrs Median LN removed: 13 Prognostic variables: # of LN removed 20% LN density,Radical Cystectomy Outcomes LN+ Disease Herr, J Urol., 169: 943, 2003.,162 LN + patients Radical Cyst + PLND Follow-up: 7.5 yrs Median LN re

35、moved: 13 Prognostic variables: # of LN removed 20% LN density,Extended Lymphadenectomy: Multicenter Prospective TrialLeissner et al., J. Urol., 171: 139, 2004.,290 cystectomies with extended LND Mapping study 81 (28%) LN + dz Median 43 LN removed Common site of mets: Obturators-40% Levels: I-below

36、common iliacs II-aortic bifurcation below III- IMA to aortic bifurcation,Extended Lymphadenectomy: Multicenter Prospective TrialLeissner et al., J. Urol., 171: 139, 2004.,Extended dissection takes 60 minutes longer No increase in morbidity or mortality For unilateral bladder tumors- contralateral no

37、dal metastases commonly occurred Lymph nodes + at level III only- do not occur Lymph nodes + at level 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”,SURGICAL

38、FACTORS IN BLADDER CANCERHerr H., BJU, 92: 187, 2003.,Factors evaluated in the neoadjuvant MVAC trial* 270 randomized patients: 24 no LND 98 limited LND 146 standard LND Median # of LN removed: 10 LNs Survival: 44% if 10 LN removed,*Grossman et al, N Eng J Med, 349: 859, 2003.,SURGICAL FACTORS IN BL

39、ADDER CANCERHerr H., BJU, 92: 187, 2003.,Significant Factors in Multivariate Analysis Extent of the node dissection Number 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 tria

40、l!”,USC Lymph Node Positive Bladder Cancer Experience Prognostic Variables,Pathologic subgroups (primary tumor) Administration of adjuvant chemotherapy Total # of lymph nodes involved with tumor Total # of lymph nodes removed Lymph node density,Lymph Node Positive Bladder Cancer Conclusions,Extended

41、 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.,Lymph Node Positive Bladder Cancer Conclusions,Lymp

42、h 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.,Lymph Node Positive Bladder Cancer Extended Lymphadenectomy,Better

43、risk assessment for LN+ patients: pathologic subgroup (p-stage) # of lymph nodes removed # of lymph nodes involved with tumor lymph node density Adjuvant chemotherapy: based on risk assessment clinical trials,USC BLADDER CANCER EXPERIENCE RADICAL CYSTECTOMY Conclusions,Best survival results Low loca

44、l (pelvic) recurrence (7%) Lowest incidence of developing metastatic or progressive disease (29%),USC BLADDER CANCER EXPERIENCE RADICAL CYSTECTOMY Conclusions,Improved morbidity and mortality Urinary reconstructive options available and improving Equally effective therapies have not emerged,USC BLAD

45、DER CANCER EXPERIENCE,“Radical cystectomy remains the preferred form of definitive therapy for invasive bladder cancer.”,Donald G. Skinner,USC BLADDER CANCER EXPERIENCE Reality,“There is a significant error in clinical staging of invasive bladder cancer.”,PRIMARY TREATMENT GOALS OF MUSCLE INVASIVE B

46、LADDER CANCER,Patient survival Prevent consequences of pelvic progression/recurrence Prevent consequences of metastatic disease,USC BLADDER CANCER EXPERIENCE Complications by Adjuvant Therapy,BLADDER CANCER: INDICATIONS FOR RADICAL CYSTECTOMY,Muscle invasive tumor,BLADDER CANCER: INDICATIONS FOR RAD

47、ICAL CYSTECTOMY,Muscle invasive tumor High grade tumor with cis,BLADDER CANCER: INDICATIONS FOR RADICAL CYSTECTOMY,Muscle invasive tumor High grade tumor with cis cis unresponsive to intravesical therapy,BLADDER CANCER: INDICATIONS FOR RADICAL CYSTECTOMY,Muscle invasive tumor High grade tumor with c

48、is cis unresponsive to intravesical therapy Recurrent multifocal high grade tumors unresponsive to intravesical therapy,BLADDER CANCER: INDICATIONS FOR RADICAL CYSTECTOMY,Muscle invasive tumor High grade tumor with cis cis unresponsive to intravesical therapy Recurrent multifocal high grade tumors unresponsive to intravesical therapy Endoscopically uncontrollable tumors,BLADDER CANCER: INDICATIONS FOR RADICAL CYSTECTOMY,Muscle invasive tumor High grade tumor with cis cis unr