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: 31.1mortality: 12.1 Seventh most common cancer in women –Incidence: 9.5mortality: 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 StageTNM5-y. Survival 0Ta/TisNoMo>85% IT1NoMo65-75% IIT2a-b NoMo57% IIIT3a-4aNoMo31% IVT4bNoMo24% each TN+Mo14% each TM+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 G1G2G3 Relapse rate42%50%80% Progression rate2%11%45%

8. Superficial Bladder Cancer Adjuvant Therapy Reduces relpase rate by 30-80% –Doxorubicinweekly 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 StageRecurrence-FreeOverall Survival 5 y.10y.5 y.10y. T2N-89877757 N+50505252 T3aN-78766444 N+41374026 T3bN-62614929 N+29292412 T4aN-50454423 N+33332620 Stein et al JCO 2001;19:666

11. Results of radical cystectomy StageRecurrence-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

12. Chemotherapy for bladder cancer Bladder cancer is a chemosensitive disease Active single agents. RR –Cisplatin30% –Carboplatin20% –Gemcitabine20-30% –Ifosfamide20%

13. Chemotherapy for bladder cancer Combination chemotherapy. RRCR –MVAC40-75%<20% –Gemzar / Cisplatin40-70%5-15% –Gemzar / Carboplatin65%5% –Taxol / Carboplatin20-40%

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 5y.OS Radiotherapy57%47% RT and cisplatin85%69% RT and carboplatin70%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 + CTcystectomy

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

20. Results of bladder-sparing therapy and cystectomy Bladder-sparing n Pat.5y. OS 5y. Survival therapy % with Bladder % Houssett 199712063 NA Sauer 19981625544 Shipley 19981234938 Shipley 20021905445 Rodel 20024155042 Cystectomy Dalbagni 200118136NA Stein 200163348NA

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 remission72% Local control after CR64% (10 y.) distant metastasis35% (10 y.) Disease-specific survival42% (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 Survival50-65% Preservation of Bladder38-43%