1. All the truth about local treatment options T1-T2 RADIOTHERAPY Anders Widmark, Professor, Senior Consultant Department of Radiation Sciences, ONCOLOLGY, Umeå University Hospital Paid Consultant, sanofi-aventis, part time Advisory boards: Astellas, Roche and Janssen European School of Oncology Educational Cancer Convention Lugano (ECCLU): What is New and What is True in Genito-Urinary Oncology? 12-14 May 2011, Lugano, Switzerland ECCLU 2011

2. Philosophy : Risk adapted Treatment with EBRT - Decrease side-effects in low risk tumor – Increase treatment in aggressive tumors Technical Development Dose-escalation, Results IGRT, IMRT 3D-CRT Margins, MRI, CT New techniques to decrease rectal toxicity Combination of hormones SPCG-7/SFUO-3 Hormones vs. Hormones + EBRT Side-effects Overview ECCLU 2011

3. Historical Radiotherapy of PC Onk klin, NUS, A W 0002 ECCLU 2011

4. Dosescalation 65Gy -> 70Gy -> 78 Gy HDR + EBRT IGRT Improved Precision, Tighter Margins Image Guided RadioTherapy IMRT Concave forms, Tighter Marigins Intensity Modulated RadioTherapy MRI Improved Target Deliniation, Established Technical Improvments ECCLU 2011

6. ALL 393 664 843 301 202 104 GETUG 306 Viani et al IJROBP 2009

7. Low Risk Inter M Risk High Risk Viani et al IJROBP 2009

8. Viani et al IJROBP 2009

9. Viani et al IJROBP 2009

12. MD anderson Trial Kuban et al Röda 2008 ECCLU 2011 78% 39% 78% 59%

14. Onk. AW 0308 PROT 05 Update 8.9 y. Zietman et al JCO 2010

15. Onk. AW 0308 32.4% 17.4% PROT 05 Update 8.9 y. Zietman et al JCO 2010

16. Onk. AW 0308 28.2% 7.1% 42.1% 30.4% PROT 05 Update 8.9 y. Zietman et al JCO 2010 Low Risk InterMed. Risk

17. Side –Effects Dose –Escalation MRC RT01 Trial , Syndikus at al IJROBP 2009 ECCLU 2011

19. BeamCath for IGRT Prostata cancer Onk. AW 9809 CT-bild ECCLU 2011

21. Prostate EBRT IGRT Onk klin, NUS, A W 0002 7 mm ECCLU 2011

22. “ Picture verified” radioterapi (IGRT) Röntgenrör Detektor ECCLU 2011

23. Dose plan ECCLU 2011

24. Rectum and dose distribution

25. Rectum dose volume histograms QUANTEC objectives

26. GPS in Prostate Calypso, Micropos ECCLU 2011

27. MR/CT

28. MR-Bild Onk klin, NUS, A W 9602 ECCLU 2011

29. Prostate MRI Cancer (S Johansson) Axial Coronal ECCLU 2011

30. Umeå Trial 1 A randomized Trial Extern Beam RT v.s. Deferred Treatment in Localized Prostate Cancer Inclusion Criteria < 75 years T1b-T2, pN0, G1-G2, M0 Inclusion within 3 mo. from diagnosis Surgical staging (obturator) Bonescan, Pulm X-ray No previous treatment ECCLU 2011

31. Umeå Trial 1 Inklusion 1986- 1996 > 20 års FU Rand studie, Sweden, Denmark, Norway WW v.s. RT Patienter 107 107 ECCLU 2011

32. HYPO-fractionation alpha/beta value in PC HYPO-RT-PC -Study Fractionation schedule under development Yeho Lukka B&R

33. Onk. AW 0609 Hypofractionationated treatments ECCLU 2011

35. Blood in Stools With Smaller margins ECCLU 2011

36. Treatment Effect are improving What about Side-effects? ECCLU 2011

37. Biverkningar - Funding ECCLU 2011

38. N 603 292 306 - Age 59 69 65 - PSA 6.7 9.1 5.8 Side-Effects - Sexual ECCLU 2011

39. Side-Effects - URIN - Funding ECCLU 2011

40. Side-Efects – Bowel - Vitality ECCLU 2011

41. Intestinal Symptoms EBRT Fig. 2 ECCLU 2011

42. Rectal leakage - When? Q31 ECCLU 2011

43. Localized PC! Local Cure is Achivable ! Improve Techniques to Decrease Rectal Toxicity!! ECCLU 2011

44. Prada et al Brachytherapy , 2007, 2009 ECCLU 2011

45. Principal of the No-HARM study Needel operated Hyaluronic Acid for Rectal Move HA 10% 50% 70% 10% 70% 50% ECCLU 2011

46. ECCLU 2011

47. ECCLU 2011 Before RT 20 treatments ./40 G

48. ECCLU 2011

49. ECCLU 2011

50. Rectal fixation probe! ECCLU 2011

51. Rectal fixation probe! ECCLU 2011

52. Hydrodissection of the space between rectum and prostate ECCLU 2011 Pro-Space: Novel Biodegradable Inflatable Balloon System

53. BLADDER PENIS RECTUM ECCLU 2011 Pro-Space: Novel Biodegradable Inflatable Balloon System

54. Lymph Node treatment? ECCLU 2011

55. Lymph Node treatment, IMRT? ECCLU 2011

56. Lymph Node treatment, VMAT? ECCLU 2011

57. Lymph Node treatment? RTOG 0924 And PIVOTAL RT + HORMONES vs RT + HORMONES + Lymph Node Iradiation ECCLU 2011

59. - Funding PSA recurrence-free survival T1b-T2, PSA < 50; Grad I-II (“SPCG-4 population”) Combination (n=69) Antiandrogen (n=64) HR 0.10 (0.04, 0.24); p>0.0001 ECCLU 2011

60. - Funding Prostate Cancer specific survival T1b-T2, PSA < 50; Grad I-II (“SPCG-4 population”) Combination (n=69) Antiandrogen (n=64) HR 0.21 (0.04, 1.00); p<0.03 ECCLU 2011

61. - Funding Overall survival T1b-T2, PSA < 50; Grad I-II (“SPCG-4 population”) Combination (n=69) Antiandrogen (n=64) HR 0.69 (0.34, 1.39); p<0.30 ECCLU 2011

66. RT 70 Gy + 6 m. ADT Intermediate risk No/mild comorbidity Moderate/ severe comor

67. RT 70 Gy + 6 m. ADT High Risk No/mild comorbidity Moderate/ severe comor

68. Summary Localised PC! Local Cure is ”Achivable (-ed)” New Radiotherapy Tecniques To further Decrease Rectal Toxicity!! ECCLU 2011

69. Conclusions Radiotherapy Local Cure is Achivable!! Dose escalation ! IGRT, IMRT Improved precision - smaller margins Less Rectal Toxicity? HYPO - Shorter Treatment time? Low Doctor time Low Cost treatment ECCLU 2011

70. Thank You! ECCLU 2011

71. Tack! Frågor ? ECCLU 2011

72. A Randomized Trial Comparing Antiandrogens With Or Without Radiotherapy In The Treatment Of Locally Advanced Prostate Cancer: Survival and Qol Outcome A. Widmark , O. Klepp, P. Fransson, J. Damber, A. Angelsen, A. Solberg, J. Lund, M. Hoyer, F Wiklund, S.D. Fosså On Behalf of SPCG-7/SFUO-3 Study Group Scandinavian Prostate Cancer Group and Swedish Association of Urological Oncology ASTRO, 2008, Plenary Session, The Lancet ECCLU 2011

73. Cumulative incidence of PSA Recurrence 74.7 % (69.6 - 79.8) 71.1 (66.3-75.9) 25.9 % (19.3 - 32.6) p<0.00001 Combination 17.6 % (13.6-21.5) Why this huge benefit? Local control is important? Seeding of cancer cells? Abscopla effect? Vaccination/immunstimulation? ECCLU 2011

74. Cumulative incidence of Prostate Cancer mortality 11.9% (7.4 -16.5) p=0.00003 23.9% (18.4 - 29.4) 9.9 (7.1-5.9) 6.3 % (3.9-8.6) ASTRO, 2008, Plenary Session ECCLU 2011

75. Cumulative incidence of Prostate Cancer mortality 9.9 (7.1-5.9) 6.3 % (3.9-8.6) ASTRO, 2008, Plenary Session ECCLU 2011 SPCG-4