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 cancerpTa, pTis, pT1

• 10-15% muscle-invasive bladder

cancerpT2, pT3, pT4

• 5% metastatic bladder cancerN+, M+

Bladder cancer: Stage and Prognosis

Stage TNM 5-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 important

G1 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.

T2 N- 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

• Radiotherapy 57% 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 protocol

Transurthral 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 42

Cystectomy

Dalbagni 2001 181 36 NAStein 2001 633 48 NA

Combined-modality treatment and organ preservation in invasive

bladder cancer

Rödel 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%