Bladder Cancer

R. Zenhäusern

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 >70%: > 65 y of age

Bladder cancer: Histology

• 90-95% transitional-cell carcinoma

• 3% squamos-cell carcinoma

• 2% adenocarcinoma• <1% small-cell carcinoma

Bladder cancer: Entities• 75-85% superficial bladder cancer

pTa, pTis, pT1• 10-15% muscle-invasive bladder

cancerpT2, pT3, pT4

• 5% metastatic bladder cancerN+, M+

Bladder cancer: Stage and Prognosis

Stage TNM5-y. Survival

0 Ta/Tis NoMo >85%I T1 NoMo 65-75%II T2a-b NoMo 57%III T3a-4a NoMo 31%IV T4b NoMo 24%each T N+Mo 14%each T M+ med. 6-9 Mo

Superficial Bladder Cancer

pTa, pT1, Tis• Standard of care=intravesical

Therapy transurethral resection

• Relapse rate: 70% adjuvant therapy

Superficial Bladder Cancer

• Histological grading is importantG1 G2 G3

Relapse rate 42% 50% 80%

Progression rate 2% 11% 45%

Superficial Bladder Cancer

Adjuvant 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

Invasive bladder cancer• Standard of care =

Radical cystectomy with pelvic lymphadenectomy

Only about 50% of patients with high-grade invasive disease are cured

Results of radical cystectomy

Stage Recurrence-Free Overall Survival5 y. 10y. 5 y. 10y.

T2N- 89 87 77 57N+ 50 50 52 52

T3a N- 78 76 64 44N+ 41 37 40 26

T3b N- 62 61 49 29N+ 29 29 24 12

T4a N- 50 45 44 23N+ 33 33 26 20

Stein et al JCO 2001;19:666

Results of radical cystectomy

Stage Recurrence-Free /Overall Survival 5 years

Organ-confined (<pT2pNo) 73% 62%

non-organ-confined (>pT2pNo) 56% 49%

Positiv lymph nodes (pT1-4, pN+) 33% 24%

Madersbacher et al JCO 2003;21:690

Chemotherapy for bladder cancer

• Bladder cancer is a chemosensitive disease

• Active single agents.RR

– Cisplatin 30%– Carboplatin 20%– Gemcitabine 20-30%– Ifosfamide 20%

Chemotherapy for bladder cancer

Combination chemotherapy.RR CR

– MVAC 40-75% <20%– Gemzar / Cisplatin 40-70% 5-15%– Gemzar / Carboplatin 65% 5%– Taxol / Carboplatin 20-40%

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

Neoadjuvant chemotherapy

• Meta-analysis of ten randomised trials (2688 patients)

13% reduction in risk of death5% absolute benefit at 5 yearsOS increased from 45% to 50%

ABC Meta-analysis Collaboration. Lancet 2003;361:1927

Combined Radio- and Chemotherapy

CR 5y.OS

• Radiotherapy57% 47%

• RT and cisplatin 85% 69%

• RT and carboplatin 70% 57%

Birkenhake et al. Strahlenther Onkol 1998;174:121

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

Bladder-sparing protocolTransurthral resection

Induction Therapy: Radiation + chemotherapy

(cisplatin, paclitacel)

Cystoscopy after 1 month

no tumor tumor

Consolidation: RT + CT cystectomy

Bladder-sparing protocol

Shiply et al. Urology 2002;60:62

T2: 5y / 10y OS: 74% / 66%

T3-T4a: 5y / 10y OS: 53% / 52%

Results of bladder-sparing therapy and cystectomy

Bladder-sparing n Pat. 5y. OS 5y. Survivaltherapy % with Bladder %

Houssett 1997 120 63 NASauer 1998 162 55 44Shipley 1998 123 49 38Shipley 2002 190 54 45Rodel 2002 415 50 42CystectomyDalbagni 2001 181 36 NAStein 2001 633 48 NA

Combined-modality treatment and organ preservation in invasive

bladder cancerRödel et al. JCO 2002;20:3061

415 patients with T1 high-risk, T1-4, No-1

Treatment: 1. Transurethral resection

2. RT (n=126), RCT (n=289) RT median 54 Gy, CT cisplatin week 1,

5

3. Restaging-TUR

Combined-modality treatment and organ preservation in invasive

bladder cancer

• Rödel et al. JCO 2002;20:3061

• Complete remission 72%• Local control after CR 64% (10 y.)• distant metastasis 35% (10 y.)• Disease-specific survival 42% (10 y.)• Preservation of bladder >80%

Local control Distant metastasis

Rödel et al. JCO 2002;20:3061

Disease-specific survival for patients after salvage cystectomy

50% 45%

21% 18%

Rödel et al. JCO 2002;20:3061

TUR and adjuvant Radio-Chemotherapy

• 5 year Survival 50-65%

• Preservation of Bladder38-43%