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Management of T1G3 Bladder cancer

Management of T1G3 Bladder cancer. Dr Charles Chabert. T1G3. High grade lesion with invasion between epithelium & muscularis propria Gene alterations similar to T2 TCC Dilemma is to identify which will be cured by TUR & which will progress. Turner E Urol 45 (2004) 401-405.

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Management of T1G3 Bladder cancer

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  1. Management of T1G3 Bladder cancer Dr Charles Chabert

  2. T1G3 High grade lesion with invasion between epithelium & muscularis propria Gene alterations similar to T2 TCC Dilemma is to identify which will be cured by TUR & which will progress Turner E Urol 45 (2004) 401-405

  3. Natural History T1G3 Paucity of data on natural history of untreated T1G3 Recurrence rates 50-70% Progression rate 25-50% Heney et al J Urol 1983; 130:1083-6

  4. Diagnosis & Initial Management Is it really T1G3? Ensure muscle present Cold cut biopsies Flourescence endoscopic resection

  5. Second TUR Retrospective review of concordance of 2nd TURBT 2nd TURBT changed management in 33% If no muscle 49% upstaged to T2 J Urol 1999; 146: 316-8

  6. Second TUR Residual tumour present in 33-37% Grade & stage predictive of residual tumour Biopsy abnormal urothelium Soloway et al Urol Clin N Am (2005) 133-145

  7. Staging System Recommendation to substage T1 121 T1 G3 T1a : above muscularis mucosae T1b: below muscularis mucosae Only 6% not substaged 5yr survival 54% vs 42% Holmang et al J Urol 1997: 157; 800-3

  8. Staging System Categorised to T1a, T1b & T1c No difference in 3 yr risk of recurrence Risk of progession 6%, 33% & 55% ROP x27 if T1c & CIS Smits et al Urol 1998;86:1035-43

  9. Staging System Measured the depth of invasion 55 patients Measured from the BM to the deepest tumour cell Cutoff 1.5mm PPV >T2 95% Cheng et al. Cancer 1999:86:1035

  10. Prognostic Features Early recurrence after TUR & BCG Size Multifocality CIS Prostatic Urethra LVI Depth of Lamina Propria Invasion Rodriguez J urol 2000;163:73-8

  11. Perioperative Cytotoxic Chemotherapy 60-80% recurrence at 5 years If high grade, there is risk of progression

  12. Perioperative Cytotoxic Chemotherapy Meta-analysis: One-dose immediate postop cytotoxic chemotherapy Sylvester et al J Urol2004: 171;2186-90

  13. Materials & methods Randomised trials with primary or recurrent Ta/T1 Exclusion of CIS Sylvester et al J Urol 171, June 2004

  14. Materials & Methods Primary end point: % of patients with a recurrence in the 2 treatment arms Decrease in Odds of recurrence calculated without time to recurrence Sylvester et al J Urol 171, June 2004

  15. Results 12 trials considered 5 exclusions; 4 inadequate randomisation 1 included CIS 7 trials entered into Meta-analysis Sylvester et al J Urol 171, June 2004

  16. Trial Characteristics Accural between 1981-1994 Median F/U: 3.4 years (2-10.7 yrs) 3 trials included only primary patients 2 trials only single tumours Sylvester et al J Urol 171, June 2004

  17. Trial Characteristics 4 different drugs used Epirubicin 3 trials Mitomycin C 2 trials Thiotepa 1 trial Pirarubicin 1 trial Sylvester et al J Urol 171, June 2004

  18. Patient Characteristics 1517 eligible patients from 7 trials 1476 had F/U 748 (50.7%) TUR only & 728 (49.3%) TUR + instillation Sylvester et al J Urol 171, June 2004

  19. Tumour Characteristics Predominantly low risk 89.2% primary tumours 84.3% single tumours 67.9% Ta 9.5% G3 Sylvester et al J Urol 171, June 2004

  20. Recurrence 629 (42.6%) of 1476 patients 362 (48.4%) TUR & 267 (36.7%) TUR + Chemo Decrease of 39% in odds of recurrence Sylvester et al J Urol 171, June 2004

  21. Toxicity Mild irritative bladder symptoms in 10% Systemic toxicity extremely rare Allergic skin reactions 1-3% Sylvester et al J Urol 171, June 2004

  22. Summary NNT to prevent 1 recurrence: 8.5 One instillation cost effective Significantly reduces recurrence with minimal morbidity Sylvester et al J Urol 171, June 2004

  23. Immunotherapy BCG results in local immunological response Helper T-cells Cytotoxic t-cell activation Soloway et al Urol Clin N Am (2005) 133-145

  24. T1G3 BCG era “Rule of threes” 1/3 survive with bladder 1/3 survive without bladder 1/3 die of their disease Studer et al J Urol 2003; 169:96-100

  25. Merits of BCG Davis et al 59% of 98 patients bladder retention at 10 years Herr HW 50% preservation with 15 year F/U Turner E Urol 45 (2004) 401-405

  26. Merits of BCG Maintenance BCG SWOG data: reduced recurrence Poor tolerance with regimen 17% completion rate Lamm et al J Urol 2000;163:1124

  27. Role of Cystectomy: Early vs Late Conservative management associated with lifelong risk of recurrence, progression & metastasis Studer et al J Urol 2003; 169:96-100

  28. Role of Cystectomy: Early vs Late Series of 153 patients Recurrence rate 75% at 10 years 30% dead at 10 years Studer et al J Urol 2003; 169:96-100

  29. Role of Cystectomy: Early vs Late Delay in treatment affects survival: Cystectomy within or greater 3 months 55% vs 34% 5 year survival May et al scand J Urol Neph 2004

  30. Role of Cystectomy: Early vs Late Improved 15 year survival with early cystectomy Review of 90 patients Cut off 2 years Herr et al J Urol 2001,166:1296-9

  31. Role of Cystectomy: Early vs Late Immediate cystectomy if : Young Deep T1 One additional poor prognostic feature

  32. Summary Highly malignant tumour Variable & unpredictable behaviour Accurate staging & re –TUR Intravesicle immunotherapy Early cystectomy

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