膀胱癌淋巴清扫基础医学医药卫生专业资料课件

The Role of The Role of Lymphadenectomy in Lymphadenectomy in Bladder CancerBladder Cancer John P. Stein, M.D.John P. Stein, M.D. University of Southern California Keck School of University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Medicine, Norris Comprehensive Cancer Center, Los Angeles CAAngeles CA HIGH-GRADE, INVASIVE HIGH-GRADE, INVASIVE BLADDER CANCER BLADDER CANCER RealityReality “ “ Invasive bladder Invasive bladder cancer is a lethal cancer is a lethal disease.”disease.” USC BLADDER CANCER USC BLADDER CANCER EXPERIENCEEXPERIENCE Rationale for CystectomyRationale for Cystectomy Best survival resultsBest survival results Lowest local recurrence ratesLowest local recurrence rates Improved morbidity and mortalityImproved morbidity and mortality Urinary reconstruction has improved Urinary reconstruction has improved quality of life (continent and orthotopic quality of life (continent and orthotopic diversion)diversion) Equally effective forms of therapy have not Equally effective forms of therapy have not emergedemerged USC/ NORRIS BLADDER CANCER EXPERIENCEUSC/ NORRIS BLADDER CANCER EXPERIENCE Recurrence-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) 051015 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) P15)(15) (6/71-12/97) 051015 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=209) p=0.21 USC/ NORRIS BLADDER CANCER EXPERIENCE USC/ NORRIS BLADDER CANCER EXPERIENCE Recurrence-Free Survival of 244 Patients with LN+ DiseaseRecurrence-Free Survival of 244 Patients with LN+ Disease Stratified by Pathologic Subgroups (OC vs. EV)Stratified by Pathologic Subgroups (OC vs. EV) (6/71-12/97) 051015 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 USC/ NORRIS BLADDER CANCER EXPERIENCE Recurrence-Free Survival of 244 Patients with LN+ DiseaseRecurrence-Free Survival of 244 Patients with LN+ Disease Stratified by Number of Positive Nodes (8)Stratified by Number of Positive Nodes (8) (6/71-12/97) 051015 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 20%) (20%) (6/71-12/97) 051015 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+ 65 yrs vs. 65 yrs)Age (65 yrs vs. 65 yrs) 1.161.160.370.37 Gender (Female vs. Male)Gender (Female vs. Male)1.271.270.220.22 Urinary Diversion (Continent vs. Conduit)Urinary Diversion (Continent vs. Conduit)0.760.76 0.120.12 Lymph Nodes Removed (15 vs. 65 yrs vs. 65 yrs)Age (65 yrs vs. 65 yrs) 1.161.160.370.37 Gender (Female vs. Male)Gender (Female vs. Male)1.271.270.220.22 Urinary Diversion (Continent vs. Conduit)Urinary Diversion (Continent vs. Conduit)0.760.76 0.120.12 Lymph Nodes Removed (15 vs. 65 yrs vs. 65 yrs)Age (65 yrs vs. 65 yrs) 1.161.160.370.37 Gender (Female vs. Male)Gender (Female vs. Male)1.271.270.220.22 Urinary Diversion (Continent vs. Conduit)Urinary Diversion (Continent vs. Conduit)0.760.76 0.120.12 Lymph Nodes Removed (15 vs. 65 yrs vs. 65 yrs)Age (65 yrs vs. 65 yrs) 1.161.160.370.37 Gender (Female vs. Male)Gender (Female vs. Male)1.271.270.220.22 Urinary Diversion (Continent vs. Conduit)Urinary Diversion (Continent vs. Conduit)0.760.76 0.120.12 Lymph Nodes Removed (15 vs. 20% vs. 20%)Lymph Node Density (20% vs. 20%) 2.362.3665 yrs vs. 65 yrs)Age (65 yrs vs. 65 yrs) 1.161.160.370.37 Gender (Female vs. Male)Gender (Female vs. Male)1.271.270.220.22 Urinary Diversion (Continent vs. Conduit)Urinary Diversion (Continent vs. Conduit)0.760.76 0.120.12 Lymph Nodes Removed (15 vs. 20% vs. 20%)Lymph Node Density (20% vs. 20%) 2.362.368 vs. 8)Lymph Nodes Involved (8 vs. 8)2.662.6620% vs. 20%) (20% vs. 20%) Lymph Nodes Involved Lymph Nodes Involved 1.911.910.0080.008 (8 vs. 8) (8 vs. 8) Radical Cystectomy for High Grade Radical Cystectomy for High Grade Invasive Bladder CancerInvasive Bladder Cancer LymphadenectomyLymphadenectomy 1. 1. Allows for a safe Allows for a safe anatomical dissection anatomical dissection 2. 2. Provides pathologic Provides pathologic stagingstaging 3. 3. Therapeutic benefits Therapeutic benefits 4. 4. Absolute limits of Absolute limits of dissection unknown dissection unknown ? ? Radical CystectomyRadical Cystectomy Extent of Lymphadenectomy in LN+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+64 patients with LN+ Radical Cyst + PLNDRadical Cyst + PLND If 11 If 11 LNs LNs removed:removed: n n Better local control Better local control ( 9% vs. 30%)( 9% vs. 30%) n n Improved survival Improved survival (44% vs 20%)(44% vs 20%) 0 5 10 15 20 25 30 % 11 LN Removed Local Recurrence Rate Radical CystectomyRadical Cystectomy Extent of Lymphadenectomy in LN+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+64 patients with LN+ Radical Cyst + PLNDRadical Cyst + PLND If 11 If 11 LNs LNs removed:removed: n n Better local control Better local control ( 9% vs. 30%)( 9% vs. 30%) n n Improved survival Improved survival (44% vs 20%)(44% vs 20%) Radical CystectomyRadical Cystectomy Extent of Lymphadenectomy in LN+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+64 patients with LN+ Radical Cyst + PLNDRadical Cyst + PLND If 11 If 11 LNs LNs removed:removed: n n Better local control Better local control ( 9% vs. 30%)( 9% vs. 30%) n n Improved survival Improved survival (44% vs 20%)(44% vs 20%) Radical CystectomyRadical Cystectomy Outcomes LN+ DiseaseOutcomes LN+ Disease Herr, J Urol., 169: 943, 2003.Herr, J Urol., 169: 943, 2003. 162 LN + patients162 LN + patients Radical Cyst + PLNDRadical Cyst + PLND Follow-up: 7.5 yrsFollow-up: 7.5 yrs Median LN Median LN removed: 13removed: 13 Prognostic variables:Prognostic variables: n n # of LN removed# of LN removed n n 20% LN density20% LN density Radical CystectomyRadical Cystectomy Outcomes LN+ DiseaseOutcomes LN+ Disease Herr, J Urol., 169: 943, 2003.Herr, J Urol., 169: 943, 2003. 162 LN + patients162 LN + patients Radical Cyst + PLNDRadical Cyst + PLND Follow-up: 7.5 yrsFollow-up: 7.5 yrs Median LN Median LN removed: 13removed: 13 Prognostic variables:Prognostic variables: n n # of LN removed# of LN removed n n 20% LN density20% LN density Extended Lymphadenectomy: Extended Lymphadenectomy: Multicenter Prospective TrialMulticenter Prospective Trial Leissner et al., J. Urol., 171: 139, 2004.Leissner et al., J. Urol., 171: 139, 2004. 290290 cystectomies cystectomies with with extended LNDextended LND Mapping studyMapping study 81 (28%) LN + 81 (28%) LN + dzdz Median 43 Median 43 LN LN removedremoved Common site of mets:Common site of mets: n n ObturatorsObturators-40%-40% Levels:Levels: n n I-below common I-below common iliacsiliacs n n II-aortic bifurcation II-aortic bifurcation belowbelow n n III- IMA to aortic III- IMA to aortic bifurcationbifurcation Extended Lymphadenectomy: Extended Lymphadenectomy: Multicenter Prospective TrialMulticenter Prospective Trial Leissner 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 longer No increase in morbidity or mortalityNo increase in morbidity or mortality For unilateral bladder tumors- contralateral nodal For unilateral bladder tumors- contralateral nodal metastases commonly occurredmetastases commonly occurred Lymph nodes + at level III Lymph nodes + at level III only-only- do not occur do not occur Lymph nodes + at level II only in 7%Lymph nodes + at level II only in 7% Lymph nodes + at level III occur in 13% and presacral Lymph nodes + at level III occur in 13% and presacral in 6% of all node-positive patientsin 6% of all node-positive patients “Strongly recommend an extended bilateral “Strongly recommend an extended bilateral LND in all patients undergoing cystectomyLND in all patients undergoing cystectomy” ” SURGICAL FACTORS IN SURGICAL FACTORS IN BLADDER CANCERBLADDER CANCER Herr 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 randomized patients: n n 24 no LND24 no LND n n 98 limited LND98 limited LND n n 146 standard LND146 standard LND Median # of LN removed: Median # of LN removed: 1010 LNs LNs Survival:Survival: n n 44% if 10 LN 10 LN removedremoved *Grossman et al, N Eng J Med, 349: 859, 2003. SURGICAL FACTORS IN SURGICAL FACTORS IN BLADDER CANCERBLADDER CANCER Herr H., BJU, 92: 187, 2003.Herr H., BJU, 92: 187, 2003. Significant Factors in Multivariate AnalysisSignificant Factors in Multivariate Analysis Extent of the node dissectionExtent of the node dissection Number of lymph nodes removedNumber of lymph nodes removed # of cases performed by the operating surgeon# of cases performed by the operating surgeon “Surgical factors and not chemotherapy “Surgical factors and not chemotherapy were the most important predictors of were the most important predictors of outcome in this randomized trial!”outcome in this randomized trial!” USC Lymph Node Positive USC Lymph Node Positive Bladder Cancer ExperienceBladder Cancer Experience Prognostic VariablesPrognostic Variables Pathologic subgroups (primary tumor)Pathologic subgroups (primary tumor) Administration of adjuvant Administration of adjuvant chemotherapychemotherapy Total # of lymph nodes involved with Total # of lymph nodes involved with tumortumor Total # of lymph nodes removedTotal # of lymph nodes removed Lymph node densityLymph node density Lymph Node Positive Bladder Lymph Node Positive Bladder Cancer Cancer ConclusionsConclusions Extended lymphadenectomy is an Extended lymphadenectomy is an important component in the treatment important component in the treatment of high-grade, invasive bladder cancer.of high-grade, invasive bladder cancer. Long-term survival in over Long-term survival in over 30%30% of of patients with lymph node positive patients with lymph node positive disease.disease. Certain prognostic variables stratify this Certain prognostic variables stratify this high-risk group of patients.high-risk group of patients. Lymph Node Positive Bladder Lymph Node Positive Bladder Cancer Cancer ConclusionsConclusions Lymph node densityLymph node density is a novel concept is a novel concept and prognostic indicator.and prognostic indicator. Lymph node densityLymph node density relates the lymph relates the lymph node tumor burden and the number of node tumor burden and the number of lymph nodes removed.lymph nodes removed. Future clinical trials and staging systems Future clinical trials and staging systems should consider should consider lymph node densitylymph node density. . Lymph Node Positive Bladder Lymph Node Positive Bladder Cancer Cancer Extended LymphadenectomyExtended Lymphadenectomy Better risk assessment for LN+ patients:Better risk assessment for LN+ patients: n n pathologic subgroup (p-stage)pathologic subgroup (p-stage) n n # of lymph nodes removed # of lymph nodes removed n n # of lymph nodes involved with tumor# of lymph nodes involved with tumor n n lymph node densitylymph node density Adjuvant chemotherapy:Adjuvant chemotherapy: n n based on risk assessmentbased on risk assessment n n clinical trialsclinical trials USC BLADDER CANCER USC BLADDER CANCER EXPERIENCE EXPERIENCE RADICAL CYSTECTOMYRADICAL CYSTECTOMY ConclusionsConclusions Best survival resultsBest survival results Low local (pelvic) recurrence Low local (pelvic) recurrence (7%)(7%) Lowest incidence of developing Lowest incidence of developing metastatic or progressive disease metastatic or progressive disease (29%)(29%) USC BLADDER CANCER USC BLADDER CANCER EXPERIENCE EXPERIENCE RADICAL CYSTECTOMYRADICAL CYSTECTOMY ConclusionsConclusions Improved morbidity and Improved morbidity and mortalitymortality Urinary reconstructive options Urinary reconstructive options available and improvingavailable and improving Equally effective therapies have Equally effective therapies have not emergednot emerged USC BLADDER CANCER USC BLADDER CANCER EXPERIENCEEXPERIENCE “Radical cystectomy Radical cystectomy remains the preferred remains the preferred form of definitive form of definitive therapy for invasive therapy for invasive bladder cancer.”bladder cancer.” Donald G. SkinnerDonald G. Skinner USC BLADDER CANCER USC BLADDER CANCER EXPERIENCE EXPERIENCE RealityReality “There is a significant “There is a significant error in clinical error in clinical staging of invasive staging of invasive bladder cancer.”bladder cancer.” PRIMARY TREATMENT GOALS PRIMARY TREATMENT GOALS OF MUSCLE INVASIVE BLADDER OF MUSCLE INVASIVE BLADDER CANCERCANCER Patient survivalPatient survival Prevent consequences of Prevent consequences of pelvic pelvic progression/recurrenceprogression/recurrence Prevent consequences of Prevent consequences of metastatic diseasemetastatic disease USC BLADDER CANCER USC BLADDER CANCER EXPERIENCEEXPERIENCE Complications by Adjuvant TherapyComplications by Adjuvant Therapy BLADDER CANCER: BLADDER CANCER: INDICATIONS FOR RADICAL INDICATIONS FOR RADICAL CYSTECTOMYCYSTECTOMY Muscle invasive tumorMuscle invasive tumor BLADDER CANCER: BLADDER CANCER: INDICATIONS FOR RADICAL INDICATIONS FOR RADICAL CYSTECTOMYCYSTECTOMY Muscle invasive tumorMuscle invasive tumor High grade tumor with High grade tumor with ciscis BLADDER CANCER: BLADDER CANCER: INDICATIONS FOR RADICAL INDICATIONS FOR RADICAL CYSTECTOMYCYSTECTOMY Muscle invasive tumorMuscle invasive tumor High grade tumor with High grade tumor with ciscis ciscis unresponsive to intravesical therapy unresponsive to intravesical therapy BLADDER CANCER: BLADDER CANCER: INDICATIONS FOR RADICAL INDICATIONS FOR RADICAL CYSTECTOMYCYSTECTOMY Muscle invasive tumorMuscle invasive tumor High grade tumor with High grade tumor with ciscis ciscis unresponsive to intravesical therapy unresponsive to intravesical therapy Recurrent Recurrent multifocal multifocal high grade tumors high grade tumors unresponsive to intravesical therapyunresponsive to intravesical therapy BLADDER CANCER: BLADDER CANCER: INDICATIONS FOR RADICAL INDICATIONS FOR RADICAL CYSTECTOMYCYSTECTOMY Muscle invasive tumorMuscle invasive tumor High grade tumor with High grade tumor with ciscis ciscis unresponsive to intravesical therapy unresponsive to intravesical therapy Recurrent Recurrent multifocal multifocal high grade tumors high grade tumors unresponsive to intravesical therapyunresponsive to intravesical therapy Endoscopically uncontrollable tumorsEndoscopically uncontrollable tumors BLADDER CANCER: BLADDER CANCER: INDICATIONS FOR RADICAL INDICATIONS FOR RADICAL CYSTECTOMYCYSTECTOMY Muscle invasive tumorMuscle invasive tumor High grade tumor with High grade tumor with ciscis ciscis unresponsive to intravesical therapy unresponsive to intravesical therapy Recurrent Recurrent multifocal multifocal high grade tumors high grade tumors unresponsive to intravesical therapyunresponsive to intravesical therapy Endoscopically uncontrollable tumorsEndoscopically uncontrollable tumors Tumors associated with a Tumors associated with a diverticulumdiverticulum USC/NORRIS BLADDER CANCER EXPERIENCE Overall and Recurrence-Free Survival for Patients with LN+ Disease (N = 244) (6/71-12/97) 0123456789101112131415 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 Pelvic-IliacPelvic-Iliac Lymphadectomy Lymphadectomy 2 cm above aorta2 cm above aorta Pelvic-IliacPelvic-Iliac Lymphadectomy Lymphadectomy ObturatorObturator fossa fossa with nerve with nerve USC/Norris Lymph Node Positive USC/Norris Lymph Node Positive Bladder Cancer ExperienceBladder Cancer Experience Primary Bladder TumorPrimary Bladder Tumor USC/Norris Lymph Node Positive USC/Norris Lymph Node Positi