Bladder'Cancer'in'the' Elderly

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1 4/20/15 Bladder'Cancer'in'the' Elderly Hamidreza)Abdi,)MD,FEBU Clinical) Fellow Department) of)urologic)sciences UBC April&2015 Objectives! 1.1Review1changing1demographics1of1patients1with1 bladder1cancer1as1the1general1population1 ages.! 2.1Review1treatment1outcomes1of1geriatric1patients1 with1muscle1 invasive1 bladder1cancer1in1comparison1 patients.! 3.1Review1clinical1tools1for1assessment1of1the1geriatric1 patient1undergoing1oncologic1treatment. 1

2 4/20/15 Bladder1cancer! 70,530 new1cases1of1bladder1cancer/year! 14,680 deaths1attributed1to1the1disease! More1than 500,0001people1in1the1United1 States1are1bladder1cancer1survivors.! Bladder1cancer1occurs1mainly1in1older1people.1 About1 91out1of1101people1with1this1cancer1are1 over1the1age1of155.1the1average1age1at1the1 time1of1diagnosis1is173. 2

3 4/20/15 Median1Age1at1Diagnosis All1sites Stomach Colon Rectum Liver Pancreas Lung Skin Breast Prostate Bladder % GU Cancer and Aging 70% 60% 50% <1 65 > % 30% 20% 10% 0% Bladder Kidney1&1Renal1 Pelvis Prostate SEER

4 4/20/15 Bladder1Cancer! a1disease1of1the1elderly 4

5 4/20/15 Other'cause,mortality, (OCM), Bladder, cancer'specific,mortality,(csm), Population 5

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7 4/20/15 / mobilesyrup.com/ In11981,1there1were1about12.41million1Canadians1aged1651and1 over,1up162%1to13.8 million1in one1out1of1every 81Canadians1is1now1a1senior. It1is1projected1that1by1the1year12026 there1will1be1over17.7 million1canadian1seniors,1or121.4%1of1the1population.1 Geriatric)Medicine) Survival) Handbook) (revised)edition)) Brian) Christopher)Misiaszek,)MD,)FRCPS)(C)) McMaster1University 7

8 4/20/15 Bladder)Cancer)in)the)Elderly Advances1in1medical1care1and1increase1in1life1 expectancy The1percentage1of1persons1aged1851years1or1 older1estimated1to1more1than1double1by1the1 year12050 Bladder1cancer1is1primarily1a1disease1of1the1 elderly1with1the1peak1incidence1occurring1at1 851years 8

9 4/20/15 cancer 9

10 4/20/15 831year1old1male1with1HTN1and1coronary1artery1 disease presented1with: Microscopic1Hematuria Smoked1401pack/1year,1quit1151years1ago mentally1fit1,lives1in1assisted1living1facility Positive1cytology Bladder1 biopsy:1cis Patients1(n=412)1treated1 with1bcg+ifn1in1a1 multicenter1phase1ii1trial Conclusions:)Aging1appears1to1be1associated1with1a1decreased1 response1to1intravesical immunotherapy1and1is1particularly apparent1in1patients1older1than1801years.1a1potential1explanation1 could1be1their1depressed1baseline1immune1status1and J1Urol. 10

11 4/20/15 Cancer1free1survival No1difference1was1observed1in1the1first1 at121years1among1patients1less1than150,1 501to159,1601to169,1701to179,1or1801years1 or1older.1after151years,127%1of1patients1 older1than1701years1were1cancer1free1 compared1with137%1younger1than1701 years1(p"=0.005). Urology. Age1<75 Age1>75 patients1751years1vs165%1in1patients1751years1(log1 trend1p".011). Urology. No1difference1in1recurrence1free1survival Difference1in1progression1free1survival1in12,101 years 11

12 4/20/15! EORTC130911! NMIBC1(n=822)! Randomized1to1BCG,1 epirubicin,1or1bcg1+1inh urothelial bladder1cancer1patients1treated1with1bcg,1 patients1>701yr prognosis;1however,1bcg1is1more1effective1than1 epirubicin independent1of1patient1age.1 Eur Urol. J1Urol. 12

13 4/20/15 Hypothesis:1 1BCG1is1less1effective1in1the1elderly1 because1of1a1waning1immune1system. Should1we1direct1elderly1patients1away1from1 BCG? 13

14 4/20/15 Muscle1invasive1Bladder1cancer 14

15 4/20/15 871y1male,1cT3N01urothelial1carcinoma PMH:1CAD,1COPD,1CaP /RT1(1997) SH:1widowed,1 independent1 in1adls/iadls Labs:1Hgb 12.6,1Albumin14.5,1Cr1123 Considering1cystectomy;1family1concerned1 about1complication1risks,1maintaining1 independence Other1considerations? 15

16 4/20/15 What1Guidelines1 don t1 mention:! Nowhere1is1this1more1clearly1demonstrated1 than1in1the1treatment1of1the1elderly1patient1 where1the1clinician1must1account1for1various1 life1concerns/expectations1and1functional1 factors1(e.g.,1surgeon1experience1and1 availability1of1medical1support1staff1and1 services). Life1expectancy1and1RC 1At1age165,1life1expectancy1is1~151years 1At1age175,1life1expectancy1is1~10 years.1 1At1age185,1life1expectancy1is1~5 years.1 1And1if1they1live1to1age195,1they1may1have1 Geriatric)Medicine) Survival) Handbook) (revised)edition)) Brian) Christopher)Misiaszek,)MD,)FRCPS)(C)) McMaster1University 16

17 4/20/15 no1generally1 accepted1 age1limit1like1the1 traditional1 rule1for1prostate1 cancer. a1life1expectancy1 of121yr has1been1suggested1to1 consider1radical1 cystectomy1for1patients1with1 muscle1invasive1bladder1cancer but1in1patients1who1are1considered1fit1for1major1 surgery1like1radical1cystectomy1and1urinary1 diversion,1life1expectancy1will1rarely1fall below1 this1level.1 Skinner1EC,1et1al.1 Urol Oncol 2007;25:66 71.! combined1seer Medicare1dataset1(patients1>1651yrs)! stage121mibc1with1no1 regional1or1distant1metastases! diagnosed1from1jan11,11992,1through1 Dec131,12002! n=

18 4/20/15 Radical1Cystectomy! 21%1(n=678)1underwent1radical1cystectomy! older1age1at1diagnosis1and1higher1comorbidity1were1 associated1with1decreased1odds1of1receiving1 cystectomy 801yrs.1vs yrs.,1OR1=10.10! Charlson comorbidityindex131vs.10 1*,1OR1=10.25! long1travel1distance1was1associated1with1decreased1 odds1of1receiving1cystectomy11>501vs.10 41miles,1OR1=

19 4/20/15 40,3881patients1181to1991years1 The1 proportion1of1patients1treated1with1cystectomy1(42.9%)1and1radiation1therapy1(16.6%)1 The1cystectomy1rate1decreased1with1age and1was1lower1in1racial/ethnic1minorities1 (especially1black1patients),1uninsured1or1medicaid1patients,1patients1residing1in1the1south1 and1northeast,1and1those1treated1at1nonteaching/research1hospitals. Eur Urol 6131( )

20 4/20/15 Curative1Therapy! National1Cancer1Data1Base! Treatment1for1MIBC1between1Jan12004,1and1 Dec12008! patients1with1MIBC1(stages1II IV)! Excluding1those1with1cT4b1tumors1or1distant1 metastases. 20

21 4/20/15 Level1I1evidence,1but.! SWOG1trial,1Grossman1et1al1NEJM12003! Median1age163! MSK1GC1vs1MVAC1series,1Dash1et1al1Cancer12008! Median1age164! et1al1jco12014! Median1age164 21

22 4/20/15 In)a)center)of)excellence,)64% of) patients,)regardless)of)age,)developed) at)least)one)complication)(although)not) usually)serious))within)90)d)after)radical) cystectomy.) Shabsigh A,1Korets R,1Vora KC,1et1al. 2009;55:

23 4/20/15 A) total)of)20)studies)were)found)that)reported perioperative)mortality)and)complication) rates)in)elderly)patients)undergoing)radical) cystectomy). Age)between)65)and)80)yr Sample) sizes)between)12)and)842 The heterogeneous definitions)of)mortality Eur1Urol. 23

24 4/20/15 Three)studies)found)significantly)increased)perioperative) mortality) in)elderly)patients Aged>701yr [Knap1MM,1et1al.12004,1Elting LS,1et1al.12005] 801yr [Yamanaka1K,1et1al.2007] Considering)blood)loss)and)transfusion)rates,)three)available) studies)suggest)some)association)with)age) [Chang1SS,1et1al.12004, Lowrance WT,et al.2008, Ca Turanzas fus More1frequent1use1of1anticoagulants Disorientation)or)delirium)may)be)expected)to)be)a) considerable)problem)in)elderly)patients)undergoing) major) surgery in)six)studies)with)a)frequency)of)5 20%. Eur1Urol Sep;56(3):443@54 The)reported)mortality)rates)in)elderly) patients)undergoing)radical)cystectomy) range)between)0%)and)11% Generally,1adapting1the1wider190@d1definition1 might1deliver1a1more1realistic1picture1of1the1risks1 of1radical1cystectomy1as1major1cancer1surgery1than1 does1reporting1apparently1excellent1but1possibly1 misleading130@d1 rates. Eur1Urol Sep;56(3):443@54 24

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26 4/20/15 Hospital)and)surgeon)volume)and)complications)after radical)cystectomy)in)elderly)patients! Surgeons! A1high1ratio1of1registered1nurses1to1patients1 including:1licensed1practical1nurses,1and1 respiratory1therapists The1best1definition1 of1such1a1 center1is1still1unclear Eur1Urol. Is)ileal neobladderan)option) in)elderly)patients?! Ileal conduit1is,1by1far,1the1most1commonly1used1 urinary1diversion1 in1this1setting.! 70%1of1cases! In1properly1selected1cases,1centers1of1excellence1 report1similar1complication1rates1in1elderly1patients,1 regardless1of1the1type1of1urinary1diversion1 Clark1PE,1et1al Sogni F,1et1al

27 4/20/15! Cutaneous)ureterostomy! Associated1with1a1decreased1risk1of1fistula1 formation1and1other1complications1 in1a1series1of1 octogenarians1! An1extraperitoneal approach1to1cystectomy Brausi1M,1et1al Ubrig B,1et1al.12004;63: Radical)cystectomy)(RC))in)octogenarians:)Long\term) experience)of)two)high)volume)institutions ASA1score131(44%),11ASA1sore141(23%) disease,1and121%1had1positive1lymph1nodes Cutaneous1 ureterostomies (67%) Ileal conduit1 (25%) Orthotopic neobladder (8%) Complication1rates1were144%,1with1significantly1fewer1 complications1seen1with1cutaneous1ureterostomy compared1to1 ileal conduit1and1neobladder formation (26%1vs149%1and145%1 respectively,1p1<10.001). Brausi M,1Selli C,1Rossi1A,1Gavioli M,1De1Luca1 G,1Peracchia G,1Verrini G,1Viola1M,1Romano1A,1 and1simonini G at)eau,)

28 4/20/15 Aging Heterogeneous process Characteristic universal changes in physiology Affects each individual at a unique pace Depletion of physiologic reserve Hallmark of Aging: Decreased Physiologic Reserve Age Physiologic Reserve = Fuel Available 28

29 4/20/15 Tools)are)Available)to)Identify)Older)Adults) at)risk)&)guide)practical)interventions Predict1toxicity1to1cancer1treatment Predict1survival1of1older1 patients1with1cancer Uncover1problems1not1detected1by1routine1H&P Leads1to1practical1interventions1 Is1it1feasible1to1incorporate1these1tools1into1 oncology1practice? Focus)on)the)elderly! Comprehensive1Geriatric1 Assessment1(CGA) functional1vs.1chronologic1age! age1and1comorbidities! multidisciplinary1 care! expanding1proportion1of1patients1receiving1 curative1therapy1by1wider1adoption1of1trimodal therapy?! better1representation1in1clinical1 trials 29

30 4/20/15 Integrating Geriatrics into Oncology Factors other than chronological age that predict morbidity & mortality in older adults Functional status Comorbid medical conditions Nutritional status Cognition Psychological state Geriatric Assessment Social support Medications (polypharmacy) Comorbidities! Elderly)patients)have)an average)of 3)diseases Chronic1 pulmonary1disease Coronary1 artery1 disease Diabetes1 Hypertension Philip1J1Shalhoub,1Marcus1L1Quek. 30

31 4/20/15 Dementia Age 80 with High Risk GU Cancer: What treatment will you recommend? 31

32 4/20/15 Chronological Age 80 Functional Age 90 Functional Age 60 Facilitating Quality Cancer Care Everyone Completes a Geriatric Assessment 32

33 4/20/15 Facilitating)Quality)Cancer)Care Facilitates Communication)and)Decision\Making Between the)oncologist/urologistand)patient Risk1Stratification1Tools Complication1/1M&M1Prediction: NSQIP1calculator Vanderbilt1 nomogram 33

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35 4/20/15 186:1829,

36 4/20/15 A1growing1body1of1accumulated1data1suggests1that1TMT1(with1 prompt1cystectomy1reserved1for1tumour1recurrence1 or1 nonresponders)1leads1to1acceptable1outcomes1and1may1 therefore1be1considered1a1reasonable1treatment1option1 selected1patients.1 the1bladder1and1limited1pelvic1lymph1nodes1to1an1initial1dose1 of1401gy,1with1a1boost1to1the1whole1bladder1to1541gy and1a1 further1tumour1boost1to1a1total1dose1of Gy.1 Eur Urol. of1large1published1cystectomy1series.1 36

37 4/20/15 Determining)Eligibility)for)Cisplatin Methods: Survey of 120 oncologists specializing in urothelial cancer Review of published literature on ineligibility for cisplatin WHO/ECOG PS of 2 Grade 2 peripheral neuropathy CrCl < 60 ml/min NYHA class III heart failure Grade 2 hearing loss (~25 db) Age alone should not be used to classify unfit patients in clinical trials Glasky1et1al,20111Mar;12(3):211@4 Key Organ Function Considerations! Renal)Function! Cardiovascular)Changes! Neuropathy! Ototoxicity! Bone)Marrow)Toxicity! A1prospective1study1in1a1healthy1population1showed1creatinine clearance1less1than1 501ml1per1minute1in112.6%1of1601to 69@year@old1patients1and1in147.3%1of1those1older1 than170 Years Nephrol Dial1Transplant12001;116:)

38 4/20/15 Age Creatinine (mg/dl) CrCl* (ml/min) Creatinine: Not an adequate measure of renal function Calculating Creatinine Clearance Cockroft &1Gault Jeliffe MDRD Wright Creatinine Clearance Equations Commonly1 used Not1validated1in1older1adults More1 accurate1in1pts1with1chronic1renal1disease Ethnicity,1 BUN,1&1albumin1are1taken1into1account Accurate1in1patients1with1GFR1>150 None are perfect All are better than creatinine alone Hurria & Lichtman, BJC

39 4/20/15 The)Past:) Risk)Factors)for)Chemotherapy)Toxicity) Patient)Factors Age ECOG"PS/KPS Labs Tumor)and)Treatment)Factors Cancer"Type Chemotherapy" Age 72 years GI/GU Cancer Standard Dose Polychemotherapy Predictors1of1Toxicity Hemoglobin (male: <11, female: <10) Creatinine Clearance (Jelliffe-ideal wt <34) Fall(s) in last 6 months Hearing impairment (fair or worse) Limited in walking 1 block (MOS) Assistance required in medication intake (IADL) Decreased social activity (MOS) Age Tumor/ Treatment Variables Labs Geriatric Assessment Variables Hurria et al, JCO

40 4/20/15 Risk of Toxicity by Score High (83%) Grade 3-5 Toxicities Low (30%) Medium (52%) Total Risk Score Hurria et al, JCO 2011 The)Present:) Geriatric)Assessment)Items) Predictive)of)Chemotherapy)Toxicity) Risk Factors Daily Activities (ADL & IADLs) Hearing (Fair or Deaf) Aaldriks Aparicio Extermann Freyer Hurria Kanesvaran Soubeyran X X X X X X X Nutrition X X X X Cognition X X X X X Psychological Status X X X X X Social Activities Aaldriks et"al,"crit Rev"Oncol Hematol 2011 Aparicio et"al,"j"clin Oncol 2013 Extermann et"al,"cancer"2012 Freyer et"al,"annals"of"oncology 2005 X Hurria et"al,"j"clin Oncol 2011 Kanesvaran et"al,"j"clin Oncol 2011" Soubeyran et"al,"j"clin Oncol

41 4/20/15 Advanced Urothelial Cancer Unfit : - Impaired renal function (GFR ml/min) - Performance status of 2 Randomize N=89 GC (Gemcitabine/ Carboplatin) Median Age: 71 (36-85) N=89 M-CAVI (Methotrexate/Carboplatin/ Vinblastine) Median Age: 72 (34-86) J1Clin1Oncol Nov120;27(33):5634@9. 41

42 4/20/15 Regimen Complete/) Partial) Response Overall) Survival Severe) Acute Toxicity Toxic)Death GC 41.2% 9.31mo. 9.3% 2.3% 30.3% 8.11mo. 21.2% 4.6% Conclusion: - No difference in response or survival - Decreased side effects with GC - PS of 2 + GFR < 60 ml/min: " 20% only received 1 cycle of tx " 26% experienced severe toxicity More clinical trials are needed The1goal1of1palliative1care1is1to1anticipate,1 prevent,1and1reduce suffering and1to1support the1best1possible1quality1of1life1for1patients and1their"families,1regardless)of)stage)of)the) disease)or1the1need1for1other1therapies.11 Palliative1care1begins)at)diagnosis)and1should1 be1delivered1concurrently1with1disease@ directed,1life@prolonging1therapies. 42

43 4/20/15 VGH)experience)2006\2014! 510 cystectomies! 203 over170! 52 over180 No1one1knows1why1we1age,1and1the1upper1 limits1of1the1human1life1span,1about11201years,1 have1not1altered1over1the1interval1of1recorded1 history1despite1advances1in1preventative1 health1care1and1medicine1 While1many1more1persons1can1live1longer1 today1because1of1these1,there1still1appears1to1 be1an1upper1limit1of1~121decades1to1our1 maximum1life1span.1 Geriatric)Medicine) Survival) Handbook) (revised)edition)) Brian) Christopher)Misiaszek,)MD,)FRCPS)(C)) McMaster1University 43

44 4/20/15 The"oldest"living"person"with"a"valid"birth" certificate"was"a"122nyearnold"woman"named" Jeanne"Calment from"france"who"was"born"in" 1875"and"who"died"in"1997." Geriatric)Medicine) Survival) Handbook) (revised)edition)) Brian) Christopher)Misiaszek,)MD,)FRCPS)(C)) McMaster1University Summary! Bladder)cancer)is)primarily)a)disease)in)the)elderly! Fast)growing)segment)of)the)population! About)half)patients)with)muscle)invasive)bladder)cancer) do)not)undergo)radical)therapy! This)number)increases)with)age! Most)elderly)patients)should)be)eligible)for)radical) cystectomy)and/or)trimodaltherapy)with)acceptable) outcomes! Presence)of)comorbidities)and)functional)status)may)be) more)important)factors)than)chronological)age)when) determining)optimal)treatment)strategies)for)elderly) patient! Comprehensive)geriatric)assessment)is)a)key)component 44

45 4/20/15 Dr Peter)Black Special)Thanks)to Thank)you! 45

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