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 >70%: > 65 y of age

3. Bladder cancer: Histology
90-95% transitional-cell carcinoma
3% squamos-cell carcinoma
2% adenocarcinoma
<1% small-cell carcinoma

4. 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+

5. Bladder cancer: Stage and Prognosis
Stage TNM 5-y. Survival
0 Ta/Tis NoMo >85%
I T1 NoMo %
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

6. Superficial Bladder Cancer pTa, pT1, Tis
Standard of care=intravesical Therapy
 transurethral resection
Relapse rate: 70%
 adjuvant therapy

7. Superficial Bladder Cancer
Histological grading is important
G1 G2 G3
Relapse rate 42% 50% 80%
Progression rate 2% 11% 45%

8. 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

9. Invasive bladder cancer
Standard of care =
Radical cystectomy with pelvic lymphadenectomy
Only about 50% of patients with high-grade invasive disease are cured

10. Results of radical cystectomy
Stage Recurrence-Free Overall Survival
5 y. 10y. 5 y. 10y.
T2 N N
T3a N N
T3b N N
T4a N N
Stein et al JCO 2001;19:666

11. Results of radical cystectomy
Stage Recurrence-Free /Overall Survival years
Organ-confined (<pT2pNo) % 62%
non-organ-confined (>pT2pNo) 56% 49%
Positiv lymph nodes (pT1-4, pN+) 33% 24%
Madersbacher et al JCO 2003;21:690

12. Chemotherapy for bladder cancer
Bladder cancer is a chemosensitive disease
Active single agents. RR
Cisplatin 30%
Carboplatin 20%
Gemcitabine 20-30%
Ifosfamide 20%

13. Chemotherapy for bladder cancer
Combination chemotherapy.
RR CR
MVAC % <20%
Gemzar / Cisplatin 40-70% 5-15%
Gemzar / Carboplatin 65% 5%
Taxol / Carboplatin 20-40%

14. 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

15. 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 2003;361:1927

16. Combined Radio- and Chemotherapy
CR y.OS
Radiotherapy 57% 47%
RT and cisplatin 85% 69%
RT and carboplatin 70% 57%
Birkenhake et al. Strahlenther Onkol 1998;174:121

17. 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

18. Bladder-sparing protocol
Transurthral resection
Induction Therapy: Radiation + chemotherapy
(cisplatin, paclitacel)
Cystoscopy after 1 month
no tumor
tumor
Consolidation: RT + CT
cystectomy

19. Bladder-sparing protocol
T2: 5y / 10y OS: 74% / 66%
T3-T4a: 5y / 10y OS: 53% / 52%
Shiply et al. Urology 2002;60:62

20. Results of bladder-sparing therapy and cystectomy
Bladder-sparing n Pat. 5y. OS y. Survival
therapy % with Bladder %
Houssett NA
Sauer
Shipley
Shipley
Rodel
Cystectomy
Dalbagni NA
Stein NA

21. 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

22. 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%

23. Local control
Distant metastasis
Rödel et al. JCO 2002;20:3061

24. Disease-specific survival for patients after salvage cystectomy
50%
45%
21%
18%
Rödel et al. JCO 2002;20:3061

25. TUR and adjuvant Radio-Chemotherapy
5 year Survival %
Preservation of Bladder 38-43%