1) Randomized trials show that for locally advanced prostate cancer, early hormone therapy combined with radiotherapy improves prostate cancer specific survival and overall survival compared to hormone therapy alone. 2) A randomized trial found that hormone therapy plus radiotherapy reduced the risk of prostate cancer death by 56% and reduced the risk of overall mortality by 23% compared to hormone therapy alone. 3) Radiotherapy is associated with improved outcomes for locally advanced prostate cancer compared to surgery, though the role of surgery remains unclear.

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

2. Locally advanced prostate cancer Randomised trials of hormone therapy Randomised trials of post-op radiotherapy Randomised trials of radiotherapy Randomised trials of surgery

3. Prostate cancer specific mortality

4. Overall mortality

5. Locally advanced prostate cancer Randomised trials of hormone therapy Randomised trials of post-op radiotherapy Randomised trials of radiotherapy Randomised trials of surgery Early hormone therapy is a standard of care

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

10. Locally advanced prostate cancer Randomised trials of hormone therapy Randomised trials of post-op radiotherapy Randomised trials of radiotherapy Randomised trials of surgery Early hormone therapy is a standard of care Local recurrence rate after surgery = 25% (or more)

11. 1996-2002 875 patients median age 66 years median PSA 16 ng/ml 78% T3 N0, M0 MAB for 3 months, then flutamide alone +/- RT to prostate (70Gy) and seminal vesicles (50Gy) with a 2cm margin Widmark et al. Lancet (2009)

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

18. Treatment Radiotherapy 45 Gy/25 F/5 weeks to pelvis 20-24 Gy/10-12 F/2-2.5 weeks to prostate If treating physician felt patient inappropriate for whole pelvis then RT given to prostate only

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!

24. Locally advanced prostate cancer Randomised trials of hormone therapy Randomised trials of post-op radiotherapy Randomised trials of radiotherapy Randomised trials of surgery Early hormone therapy is a standard of care Local recurrence rate after surgery = 25% (or more) Radiotherapy halves prostate cancer specific mortality

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)

27. Locally advanced prostate cancer Randomised trials of hormone therapy Randomised trials of post-op radiotherapy Randomised trials of radiotherapy Randomised trials of surgery Early hormone therapy is a standard of care Local recurrence rate after surgery = 25% (or more) Radiotherapy halves prostate cancer specific mortality The role of surgery remains investigational