Bladder Cancer

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Bladder Cancer

  1. 1. Bladder Cancer R. Zenhäusern
  2. 2. Bladder cancer: Epidemiology <ul><li>Incidence: 20/100000/year (Europe) </li></ul><ul><li>Mortality: 8-9/100000/year </li></ul><ul><li>Fourth most common cancer in men </li></ul><ul><ul><li>Incidence: 31.1 mortality: 12.1 </li></ul></ul><ul><li>Seventh most common cancer in women </li></ul><ul><ul><li>Incidence: 9.5 mortality: 4.5 </li></ul></ul><ul><li>At diagnosis >70%: > 65 y of age </li></ul>
  3. 3. Bladder cancer: Histology <ul><li>90-95% transitional-cell carcinoma </li></ul><ul><li>3% squamos-cell carcinoma </li></ul><ul><li>2% adenocarcinoma </li></ul><ul><li><1% small-cell carcinoma </li></ul>
  4. 4. Bladder cancer: Entities <ul><li>75-85% superficial bladder cancer </li></ul><ul><li>pTa, pTis, pT1 </li></ul><ul><li>10-15% muscle-invasive bladder cancer </li></ul><ul><li>pT2, pT3, pT4 </li></ul><ul><li>5% metastatic bladder cancer </li></ul><ul><li>N+, M+ </li></ul>
  5. 5. Bladder cancer: Stage and Prognosis <ul><li>Stage TNM 5-y. Survival </li></ul><ul><li>0 Ta/Tis NoMo >85% </li></ul><ul><li>I T1 NoMo 65-75% </li></ul><ul><li>II T2a-b NoMo 57% </li></ul><ul><li>III T3a-4a NoMo 31% </li></ul><ul><li>IV T4b NoMo 24% </li></ul><ul><li>each T N+Mo 14% </li></ul><ul><li>each T M+ med. 6-9 Mo </li></ul>
  6. 6. Superficial Bladder Cancer pTa, pT1, Tis <ul><li>Standard of care=intravesical Therapy </li></ul><ul><li> transurethral resection </li></ul><ul><li>Relapse rate: 70% </li></ul><ul><li> adjuvant therapy </li></ul>
  7. 7. Superficial Bladder Cancer <ul><li>Histological grading is important </li></ul><ul><li>G1 G2 G3 </li></ul><ul><li>Relapse rate 42% 50% 80% </li></ul><ul><li>Progression rate 2% 11% 45% </li></ul>
  8. 8. Superficial Bladder Cancer Adjuvant Therapy <ul><li>Reduces relpase rate by 30-80% </li></ul><ul><ul><li>Doxorubicin weekly 6-8 w. / monthly 6-12 </li></ul></ul><ul><ul><li>Mitomycin C weekly 6-8 w. / monthly 6-12 </li></ul></ul><ul><ul><li>BCG weekly 6-8 w. /Mo 3 and 6 </li></ul></ul>
  9. 9. Invasive bladder cancer <ul><li>Standard of care = </li></ul><ul><li>Radical cystectomy with pelvic lymphadenectomy </li></ul><ul><li>Only about 50% of patients with high-grade invasive disease are cured </li></ul>
  10. 10. Results of radical cystectomy <ul><li>Stage Recurrence-Free Overall Survival </li></ul><ul><li>5 y. 10y. 5 y. 10y. </li></ul><ul><li>T2 N- 89 87 77 57 </li></ul><ul><li>N+ 50 50 52 52 </li></ul><ul><li>T3a N- 78 76 64 44 </li></ul><ul><li>N+ 41 37 40 26 </li></ul><ul><li>T3b N- 62 61 49 29 </li></ul><ul><li>N+ 29 29 24 12 </li></ul><ul><li>T4a N- 50 45 44 23 </li></ul><ul><li>N+ 33 33 26 20 </li></ul><ul><li>Stein et al JCO 2001;19:666 </li></ul>
  11. 11. Results of radical cystectomy <ul><li>Stage Recurrence-Free /Overall Survival 5 years </li></ul><ul><li>Organ-confined ( < pT2pNo) 73% 62% </li></ul><ul><li>non-organ-confined (>pT2pNo) 56% 49% </li></ul><ul><li>Positiv lymph nodes (pT1-4, pN+) 33% 24% </li></ul><ul><li>Madersbacher et al JCO 2003;21:690 </li></ul>
  12. 12. Chemotherapy for bladder cancer <ul><li>Bladder cancer is a chemosensitive disease </li></ul><ul><li>Active single agents. </li></ul><ul><li>RR </li></ul><ul><ul><li>Cisplatin 30% </li></ul></ul><ul><ul><li>Carboplatin 20% </li></ul></ul><ul><ul><li>Gemcitabine 20-30% </li></ul></ul><ul><ul><li>Ifosfamide 20% </li></ul></ul>
  13. 13. Chemotherapy for bladder cancer <ul><li>Combination chemotherapy. </li></ul><ul><li>RR CR </li></ul><ul><ul><li>MVAC 40-75% <20% </li></ul></ul><ul><ul><li>Gemzar / Cisplatin 40-70% 5-15% </li></ul></ul><ul><ul><li>Gemzar / Carboplatin 65% 5% </li></ul></ul><ul><ul><li>Taxol / Carboplatin 20-40% </li></ul></ul>
  14. 14. Adjuvant chemotherapy <ul><li>Six randomised trials have compared CT with observation after cystectomy or RT </li></ul><ul><li>4x no survival benefit </li></ul><ul><li>2x benefit from adjuvant CT </li></ul><ul><li> no standard of care </li></ul><ul><ul><li>node positive disease, lymphovascular invasion, positive margins </li></ul></ul>
  15. 15. Neoadjuvant chemotherapy <ul><li>Meta-analysis of ten randomised trials </li></ul><ul><li>(2688 patients) </li></ul><ul><ul><li>13% reduction in risk of death </li></ul></ul><ul><ul><li>5% absolute benefit at 5 years </li></ul></ul><ul><ul><li>OS increased from 45% to 50% </li></ul></ul><ul><ul><li>ABC Meta-analysis Collaboration. Lancet 2003;361:1927 </li></ul></ul>
  16. 16. Combined Radio- and Chemotherapy <ul><li>CR 5y.OS </li></ul><ul><li>Radiotherapy 57% 47% </li></ul><ul><li>RT and cisplatin 85% 69% </li></ul><ul><li>RT and carboplatin 70% 57% </li></ul>Birkenhake et al. Strahlenther Onkol 1998;174:121
  17. 17. Bladder-sparing therapy for invasive bladder cancer <ul><li>High probability of subsequent distant metastasis after cystectomy or radiotherapy alone (50% within 2 years) </li></ul><ul><li>Radiotherapy im comparison with cystectomy has inferior results (local control 40%) </li></ul><ul><li>muscle-invasive bladder cancer is often a systemic disease </li></ul><ul><li> combined modality therapy </li></ul>
  18. 18. Bladder-sparing protocol Transurthral resection Induction Therapy: Radiation + chemotherapy (cisplatin, paclitacel) Cystoscopy after 1 month no tumor tumor Consolidation: RT + CT cystectomy
  19. 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. 20. Results of bladder-sparing therapy and cystectomy <ul><li>Bladder-sparing n Pat. 5y. OS 5y. Survival </li></ul><ul><li>therapy % with Bladder % </li></ul><ul><li>Houssett 1997 120 63 NA </li></ul><ul><li>Sauer 1998 162 55 44 </li></ul><ul><li>Shipley 1998 123 49 38 </li></ul><ul><li>Shipley 2002 190 54 45 </li></ul><ul><li>Rodel 2002 415 50 42 </li></ul><ul><li>Cystectomy </li></ul><ul><li>Dalbagni 2001 181 36 NA </li></ul><ul><li>Stein 2001 633 48 NA </li></ul>
  21. 21. Combined-modality treatment and organ preservation in invasive bladder cancer <ul><li>Rödel et al. JCO 2002;20:3061 </li></ul><ul><li>415 patients with T1 high-risk, T1-4, No-1 </li></ul><ul><li>Treatment: 1. Transurethral resection </li></ul><ul><li>2. RT (n=126), RCT (n=289) </li></ul><ul><li> RT median 54 Gy, CT cisplatin week 1, 5 </li></ul><ul><li>3. Restaging-TUR </li></ul>
  22. 22. Combined-modality treatment and organ preservation in invasive bladder cancer <ul><li>Rödel et al. JCO 2002;20:3061 </li></ul><ul><li>Complete remission 72% </li></ul><ul><li>Local control after CR 64% (10 y.) </li></ul><ul><li>distant metastasis 35% (10 y.) </li></ul><ul><li>Disease-specific survival 42% (10 y.) </li></ul><ul><li>Preservation of bladder >80% </li></ul>
  23. 23. Local control Distant metastasis Rödel et al. JCO 2002;20:3061
  24. 24. Disease-specific survival for patients after salvage cystectomy 50% 45% 21% 18% Rödel et al. JCO 2002;20:3061
  25. 25. TUR and adjuvant Radio-Chemotherapy <ul><li>5 year Survival 50-65% </li></ul><ul><li>Preservation of Bladder 38-43% </li></ul>

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