1. Ο ρόλος των μη χειρουργικών θεραπειών στο μη μεταστατικό μυοδιηθητικό καρκίνο ουροδόχου κύστεως Γεώργιος Δ. Λύπας Παθολόγος Ογκολόγος Α’ Ογκολογική Κλινική & Μονάδα Γενετικής Ογκολογίας ΔΘΚΑ ΥΓΕΙΑ

2. Clinical States Model: Bladder Cancer

3. Treatment options? Presented By Matt Galsky at 2014 ASCO Annual Meeting

4. Cystectomy is potentially curative Presented By Matt Galsky at 2014 ASCO Annual Meeting

5. Bladder cancer is a disease of the elderly Presented By Matt Galsky at 2014 ASCO Annual Meeting

6. Radical cystectomy is performed less frequently in the elderly Presented By Matt Galsky at 2014 ASCO Annual Meeting

7. Bladder Cancer: A disease of the elderly

8. What else do we need to know? Presented By Matt Galsky at 2014 ASCO Annual Meeting

9. Geriatric Assessment Presented By Matt Galsky at 2014 ASCO Annual Meeting

10. Overview Presented By Nicholas James at 2013 ASCO Annual Meeting

11. Background

12. Bladder cancer is a systemic disease

13. Neoadjuvant chemotherapy and survival

14. Neoadjuvant chemotherapy

15. MRC/EORTC Trial - Loco-regional and metastatic control

16. Is survival better after surgery? Presented By Nicholas James at 2013 ASCO Annual Meeting

17. Survival from UK Registry data

18. Survival is better after surgery?

19. Survival surgery vs radiotherapy

20. Age at diagnosis

21. Choice of treatment

22. Chemoradiation vs radiotherapy alone

23. Synchronous Chemo-radiotherapy

24. Cisplatinum and RT +/- surgery

25. BCON: Aim and endpoints

26. BCON Results

27. BC2001: Trial design

28. Chemotherapy regimen

29. Patient demographics

30. Acute toxicity

31. RTOG 6 month toxicity outcomes

32. Loco-regional disease free survival in chemotherapy randomisation

33. Slide 29

34. Patterns of recurrence after chemoRT

35. Markers for outcome

36. Baseline indicators of poor outcome with (chemo)RT

37. Can we select good responders?

38. Trimodality therapy

39. Results – Boston approach

40. MRE11 hypothesis

41. Slide 37

42. Cisplatin Toxicities

43. Impact of Renal Impairment on Eligibility for Adjuvant Cisplatin-Based Chemotherapy

44. Unfit for Cisplatin

45. Concurrent RT with non-platinum chemotherapy ● Gemcitabine 200mg/m2: twice a week (from d1) ● n=34 (elderly pts) ● T2-T4, N any ● Cystoscopy @ 6 wks – CR:13/34 ● 1y. survival 81% ● Gr3-4 toxicity: 5/34 (feb. neutropenia or dehydration) J Clin Oncol 27, 2009 (suppl; abstr e16135)

46. Outline

47. Optimization of Chemotherapy: Avoid in those unlikely to respond

48. Alterations in ATM, RB1 or FANCC predict pathologic complete response (pT0) (Plimack et al. Abstract 4538)

49. Association of ERCC2 mutations with cisplatin sensitivity in MIBC (Rosenberg et al. Abstract 4510)

50. Outline

51. Optimization of Chemotherapy: Avoid in those likely to experience toxicity

52. Induction of p16LUC Correlates with Age

53. Expression of p16 INK4a by age and prior chemotherapy exposure

54. Outline

55. Slide 29

56. Slide 30

57. Slide 2

58. Slide 3

59. Slide 12

60. Response according to PD-L1 status (on tumor cells) by IHC

61. Slide 13

62. Conclusions