1. Locally advanced prostate cancer: pro radiation Chris Parker Change Presentation title and date in Footer dd.mm.yyyy

3. Prostate cancer specific mortality

4. Overall mortality

7. bPFS

8. Biochemical progression-free survival of all patients with undetectable prostate-specific antigen after radical prostatectomy Wiegel T et al. JCO 2009;27:2924-2930 ©2009 by American Society of Clinical Oncology

12. 0 1 2 4 0 1 2 4 Time (years) 10 5 0 10 5 0 Hormones + RT Hormones alone 10 5 0 10 5 0 Fransson et al. Lancet Oncology (2009)

13. 10 5 0 10 5 0 Fransson et al. Lancet Oncology (2009) Hormones + RT Hormones alone 0 1 2 4 0 1 2 4 Time (years)

14. 0 2 4 6 8 10 100 80 60 40 20 0 Disease-specific mortality Hormones Hormones + RT Years % 24% vs 12%, RR 0.44 (CI: 0.30-0.66) Widmark et al. Lancet (2009)

15. Hormones Hormones + RT 39% vs 30%, RR 0.68 (CI: 0.52-0.89) Overall mortality Widmark et al. Lancet (2009) 0 2 4 6 8 10 100 80 60 40 20 0 Years %

16. Intergroup Randomized Phase III Study of Androgen Deprivation Therapy + Radiation Therapy in Locally Advanced Prostate Cancer NCIC CTG PR.3/ MRC PR07/ SWOG JPR3 P. R. Warde, M. D. Mason, M. R. Sydes, M. K. Gospodarowicz, G. P. Swanson, P. Kirkbride, E. Kostashuk, J. Hetherington, K. Ding, W. R. Parulekar

17. NCIC CTG PR.3/MRC PR07/SWOG JPR3: Study Scheme Continuous Androgen Deprivation Therapy + Radiotherapy Continuous Androgen Deprivation Therapy T3/T4 N0/NX or T2 and PSA > 40 μ g/L or T2 and PSA > 20 μ g/L and GS: 8-10

19. Baseline Characteristics Characteristic ADT Alone ADT+RT Median Age 69.7 years 69.7 years T Category < T2c T3/T4 11% 89% 10% 88% Gleason Score < 7 8-10 81% 18% 81% 18% PSA ng/ml <20 20-50 >50 37% 38% 25% 36% 38% 26%

20. Disease Specific Survival HR=0.57 (95% C.I. 0.37-0.78) p=0.001 140 Deaths from Prostate Cancer 89 ADT alone, 51 RT+ADT 7 yr DSS 90% 7 yr DSS 79% # at Risk ADT ADT+RT ADT ADT+RT Percentage 0 20 40 60 80 100 0 3 6 9 602 603 509 512 Time (Years) 213 232 51 60

21. Overall Survival 320 Deaths, 175 ADT alone, 145 RT+ADT HR=0.77 (95% C.I. 0.61-0.98) P=0.0331 # at Risk ADT ADT+RT ADT ADT+RT Percentage 0 20 40 60 80 100 0 3 6 9 602 603 509 512 Time (Years) 213 232 51 60 7 yr OS 74% 7 yr OS 66%

22. Late Toxicity Grade < 2 Grade > 3 Gastrointestinal Diarrhea ADT Alone 8% 0.7% ADT +RT 14% 1.3% Rectal Bleeding ADT Alone 5% 0.5% ADT +RT 12% 0.3% Genitourinary ADT Alone 42% 2.3% ADT +RT 44% 2.3%

23. Radiotherapy is getting better!

25. Impact on prostate cancer mortality 0 2 4 6 8 10 40 20 0 RT Radiotherapy (SPCG 7) Surgery (SPCG 4) 12% at 10 years 5% at 10 years RP WW Hormones RR 0.44 (CI: 0.30-0.66) RR 0.65 (CI: 0.45-0.94)

26. Impact on overall mortality 0 2 4 6 8 10 40 20 0 % Radiotherapy (SPCG 7) Surgery (SPCG 4) 9% at 10 years 7% at 12 years RR 0.68 (CI: 0.52-0.89) RR 0.82 (CI: 0.65-1.03)