1. The long term outcome of high risk non-muscle invasive bladder cancer. F Thomas, N Rubin, J Goepel, D Rosario, MF Abbod, JWF Catto. Academic unit of Urology, Sheffield Teaching Hospitals, Sheffield. Retrospective study of patients 1994-2009 High risk NMIBC(G3Ta,G3T1,(G1,G2T1),CIS) Reported case series so far are of modest size and limited follow up Relationship between clinic pathologic features and outcome were analysed Primary outcomes- progression free, disease specific survival Secondary outcomes- radical cystectomy, recurrence free survival 951 Primary high-risk UCC Included: 712 high-risk UCC Excluded: 72 pT2 on re-resection 104 <6 months follow up 54 Second opinion 9 Non-UCC

2. T2 n=110 (15.8%) (3 yrs-18%) (5yrs-26.5%) Recurrence n=402 (56.5%) RC n=91(12.8%) DSM n=134 (18.8%) (3 yrs-17.2%) (5yrs-28.7%) 4.8months17.2months 28months 14.2months Included: 712 high-risk UCC P<0.001 T2 No-T2 Cancer specific survival 72 024 96120 144 168 48 192 0.2 1 0.8 0.6 0.4 0.0 Event free survival P<0.001 T2 No-T2 Follow up ( months) 0.2 1 0.8 0.6 0.4 0.0 Ci s LG Dysplasia P<0.001 Event free survival P<0.001 Cis Normal LG Dysplasia Progression to muscle invasive disease P<0.665 No BCG BCG Event free survival 0.2 1 0.8 0.6 0.4 0.0 7202496120 144 16848192 Follow up ( months) 72 024 96120 144 168 48 192 Follow up ( months) Progression Age Dysplastic urotheliumDysplastic urothelium recurrence Death Age Stage Dyspalstic urotheliumDyspalstic urothelium

3. Conclusions Despite disparities in initial treatment (e.g. induction versus maintenance BCG versus chemotherapy), around 1 in 4 patients with high-risk NMI tumors progress to muscle invasion within 5 years of diagnosis. T2 progression increased DSM more than five fold when compared to non-progressing patients. Consequently, the long-term cure rate from radical treatment dropped from 90-91% to 48.6% with muscle invasion. BCG does not reduce progression in these tumors, suggesting a need to change in treatment strategy Our data enlarge the literature base and reveal consistency in outcomes that suggests a change in management for these tumors is required.

5. Cox regression analysis - progression Univariable Multivariable

6. Cox regression analysis - Death Univariable Multivariable

7. The long term outcome of high risk non-muscle invasive bladder cancer. F Thomas, N Rubin, J Goepel, D Rosario, MF Abbod, JWF Catto. Academic unit of Urology, Sheffield Teaching Hospitals, Sheffield.