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Bladder Cancer

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

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Bladder Cancer

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  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 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

  6. Superficial Bladder CancerpTa, 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 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

  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- 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 2001;19:666

  11. 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

  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 40-75% <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 5y.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-invasivebladder 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 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

  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 50-65% • Preservation of Bladder 38-43%

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