Bladder Cancer

1
Bladder Cancer

• R. Zenhäusern

2
Bladder cancer Epidemiology

• Incidence 20/100000/year (Europe)
• Mortality 8-9/100000/year
• Fourth most common cancer in men
• Incidence 31.1 mortality 12.1
• Seventh most common cancer in women
• Incidence 9.5 mortality 4.5
• At diagnosis gt70 gt 65 y of age

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Bladder cancer Histology

• 90-95 transitional-cell carcinoma
• 3 squamos-cell carcinoma
• 2 adenocarcinoma
• lt1 small-cell carcinoma

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Bladder cancer Entities

• 75-85 superficial bladder cancer
• pTa, pTis, pT1
• 10-15 muscle-invasive bladder cancer
• pT2, pT3, pT4
• 5 metastatic bladder cancer
• N, M

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Bladder cancer Stage and Prognosis

• Stage TNM 5-y. Survival
• 0 Ta/Tis NoMo gt85
• I T1 NoMo 65-75
• II T2a-b NoMo 57
• III T3a-4a NoMo 31
• IV T4b NoMo 24
• each T NMo 14
• each T M med. 6-9 Mo

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Superficial Bladder CancerpTa, pT1, Tis

• Standard of careintravesical Therapy
• ? transurethral resection
• Relapse rate 70
• ? adjuvant therapy

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Superficial Bladder Cancer

• Histological grading is important
• G1 G2 G3
• Relapse rate 42 50 80
• Progression rate 2 11 45

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Superficial Bladder CancerAdjuvant Therapy

• Reduces relpase rate by 30-80
• Doxorubicin weekly 6-8 w. / monthly 6-12
• Mitomycin C weekly 6-8 w. / monthly 6-12
• BCG weekly 6-8 w. /Mo 3 and 6

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Invasive bladder cancer

• Standard of care
• Radical cystectomy with pelvic lymphadenectomy
• Only about 50 of patients with high-grade
  invasive disease are cured

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Results of radical cystectomy

• Stage Recurrence-Free Overall Survival
• 5 y. 10y. 5 y. 10y.
• T2 N- 89 87 77 57
• N 50 50 52 52
• T3a N- 78 76 64 44
• N 41 37 40 26
• T3b N- 62 61 49 29
• N 29 29 24 12
• T4a N- 50 45 44 23
• N 33 33 26 20
• Stein et al JCO 200119666

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Results of radical cystectomy

• Stage Recurrence-Free /Overall Survival 5
  years
• Organ-confined (ltpT2pNo) 73 62
• non-organ-confined (gtpT2pNo) 56 49
• Positiv lymph nodes (pT1-4, pN) 33 24
• Madersbacher et al JCO 200321690

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Chemotherapy for bladder cancer

• Bladder cancer is a chemosensitive disease
• Active single agents.
• RR
• Cisplatin 30
• Carboplatin 20
• Gemcitabine 20-30
• Ifosfamide 20

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Chemotherapy for bladder cancer

• Combination chemotherapy.
• RR CR
• MVAC 40-75 lt20
• Gemzar / Cisplatin 40-70 5-15
• Gemzar / Carboplatin 65 5
• Taxol / Carboplatin 20-40

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Adjuvant chemotherapy

• Six randomised trials have compared CT with
  observation after cystectomy or RT
• 4x no survival benefit
• 2x benefit from adjuvant CT
• ? no standard of care
• node positive disease, lymphovascular invasion,
  positive margins

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Neoadjuvant chemotherapy

• Meta-analysis of ten randomised trials
• (2688 patients)
• 13 reduction in risk of death
• 5 absolute benefit at 5 years
• OS increased from 45 to 50
• ABC Meta-analysis Collaboration. Lancet
  20033611927

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Combined Radio- and Chemotherapy

• CR 5y.OS
• Radiotherapy 57 47
• RT and cisplatin 85 69
• RT and carboplatin 70 57

Birkenhake et al. Strahlenther Onkol 1998174121
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Bladder-sparing therapy for invasive bladder
cancer

• High probability of subsequent distant metastasis
  after cystectomy or radiotherapy alone (50
  within 2 years)
• Radiotherapy im comparison with cystectomy has
  inferior results (local control 40)
• muscle-invasive bladder cancer is often a
  systemic disease
• ? combined modality therapy

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Bladder-sparing protocol
Transurthral resection
Induction Therapy Radiation chemotherapy
(cisplatin, paclitacel)
Cystoscopy after 1 month
no tumor
tumor
Consolidation RT CT
cystectomy
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Bladder-sparing protocol
T2 5y / 10y OS 74 / 66
T3-T4a 5y / 10y OS 53 / 52
Shiply et al. Urology 20026062
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Results of bladder-sparing therapy and cystectomy

• Bladder-sparing n Pat. 5y. OS 5y.
  Survival
• therapy with Bladder
• Houssett 1997 120 63 NA
• Sauer 1998 162 55 44
• Shipley 1998 123 49 38
• Shipley 2002 190 54 45
• Rodel 2002 415 50 42
• Cystectomy
• Dalbagni 2001 181 36 NA
• Stein 2001 633 48 NA

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Combined-modality treatment and organ
preservation in invasive bladder cancer

• Rödel et al. JCO 2002203061
• 415 patients with T1 high-risk, T1-4, No-1
• Treatment 1. Transurethral resection
• 2. RT (n126), RCT (n289)
• RT median 54 Gy, CT cisplatin week 1, 5
• 3. Restaging-TUR

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Combined-modality treatment and organ
preservation in invasive bladder cancer

• Rödel et al. JCO 2002203061
• Complete remission 72
• Local control after CR 64 (10 y.)
• distant metastasis 35 (10 y.)
• Disease-specific survival 42 (10 y.)
• Preservation of bladder gt80

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Local control
Distant metastasis
Rödel et al. JCO 2002203061
24
Disease-specific survival for patients after
salvage cystectomy
50
45
21
18
Rödel et al. JCO 2002203061
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TUR and adjuvant Radio-Chemotherapy

• 5 year Survival 50-65
• Preservation of Bladder 38-43