Bladder Cancer R Zenhusern Bladder cancer Incidence Mortality

Bladder Cancer R. Zenhäusern

Bladder cancer: • Incidence: • Mortality: Epidemiology 20/100000/year (Europe) 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% • 2% • <1% squamos-cell carcinoma adenocarcinoma small-cell carcinoma

Bladder cancer: Entities • 75 -85% superficial bladder cancer p. Ta, p. Tis, p. T 1 • 10 -15% muscle-invasive bladder cancer p. T 2, p. T 3, p. T 4 • 5% metastatic bladder cancer N+, M+

Bladder cancer: Stage and Prognosis Stage TNM 5 -y. Survival 0 Ta/Tis No. Mo >85% I T 1 No. Mo 65 -75% II T 2 a-b No. Mo 57% III T 3 a-4 a No. Mo 31% IV T 4 b each T No. Mo N+Mo M+ 24% 14% med. 6 -9 Mo

Superficial Bladder Cancer p. Ta, p. T 1, Tis • Standard of care=intravesical Therapy transurethral resection • Relapse rate: 70% adjuvant therapy

Superficial Bladder Cancer • Histological grading is important G 1 G 2 G 3 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 highgrade invasive disease are cured

Results of radical cystectomy Stage T 2 T 3 a T 3 b T 4 a NN+ NN+ Recurrence-Free 5 y. 10 y. Overall Survival 5 y. 10 y. 89 50 78 41 62 29 50 33 77 52 64 40 49 24 44 26 87 50 76 37 61 29 45 33 57 52 44 26 29 12 23 20 Stein et al JCO 2001; 19: 666

Results of radical cystectomy Stage Recurrence-Free /Overall Survival 5 years Organ-confined (<p. T 2 p. No) 73% 62% non-organ-confined (>p. T 2 p. No) 56% 49% Positiv lymph nodes (p. T 1 -4, p. N+) 33% 24% Madersbacher et al JCO 2003; 21: 690

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

Chemotherapy for bladder cancer Combination chemotherapy. – – MVAC Gemzar / Cisplatin Gemzar / Carboplatin Taxol / Carboplatin RR CR 40 -75% 40 -70% 65% 20 -40% <20% 5 -15% 5%

Adjuvant chemotherapy • Six randomised trials have compared CT with observation after cystectomy or RT • 4 x no survival benefit • 2 x 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 death 5% absolute benefit at 5 years OS increased from 45% to 50% ABC Meta-analysis Collaboration. Lancet 2003; 361: 1927

Combined Radio- and Chemotherapy CR 5 y. 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 Consolidation: RT + CT tumor cystectomy

Bladder-sparing protocol T 2: 5 y / 10 y OS: 74% / 66% T 3 -T 4 a: 5 y / 10 y OS: 53% / 52% Shiply et al. Urology 2002; 60: 62

Results of bladder-sparing therapy and cystectomy Bladder-sparing n Pat. therapy 5 y. OS % 5 y. Survival with Bladder % Houssett 1997 120 63 NA Sauer 1998 Shipley 2002 Rodel 2002 162 123 190 415 55 49 54 50 44 38 45 42 Dalbagni 2001 181 36 NA Stein 2001 633 48 NA Cystectomy

Combined-modality treatment and organ preservation in invasive bladder cancer Rödel et al. JCO 2002; 20: 3061 415 patients with T 1 high-risk, T 1 -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 Local control after CR 64% distant metastasis Disease-specific survival Preservation of bladder 72% (10 y. ) 35% (10 y. ) 42% (10 y. ) >80%