Locally advanced prostate cancer: pro radiation Chris Parker Change Presentation title and date in Footer dd.mm.yyyy
Locally advanced prostate cancer <ul><li>Randomised trials of hormone therapy </li></ul><ul><li>  </li></ul><ul><li>Random...
Prostate cancer specific mortality
Overall mortality
Locally advanced prostate cancer <ul><li>Randomised trials of hormone therapy </li></ul><ul><li>  </li></ul><ul><li>Random...
bPFS
Biochemical progression-free survival of all patients with undetectable prostate-specific antigen after radical prostatect...
Locally advanced prostate cancer <ul><li>Randomised trials of hormone therapy </li></ul><ul><li>  </li></ul><ul><li>Random...
<ul><ul><li>1996-2002  </li></ul></ul><ul><ul><li>875 patients </li></ul></ul><ul><ul><ul><li>median age 66 years </li></u...
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 Oncolo...
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)
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-...
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...
Intergroup Randomized Phase III Study of Androgen Deprivation Therapy  +  Radiation Therapy in Locally Advanced  Prostate ...
NCIC CTG PR.3/MRC PR07/SWOG JPR3: Study Scheme Continuous   Androgen  Deprivation Therapy   +  Radiotherapy Continuous And...
Treatment <ul><li>Radiotherapy </li></ul><ul><ul><li>45 Gy/25 F/5 weeks to pelvis </li></ul></ul><ul><ul><li>20-24 Gy/10-1...
Baseline Characteristics Characteristic ADT Alone ADT+RT Median Age 69.7 years 69.7 years T Category <  T2c T3/T4 11% 89% ...
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 ...
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 AD...
Late Toxicity Grade  <  2 Grade  >  3 Gastrointestinal Diarrhea ADT Alone 8% 0.7% ADT +RT 14% 1.3% Rectal Bleeding ADT Alo...
Radiotherapy is getting better!
Locally advanced prostate cancer <ul><li>Randomised trials of hormone therapy </li></ul><ul><li>  </li></ul><ul><li>Random...
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 ...
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 ...
Locally advanced prostate cancer <ul><li>Randomised trials of hormone therapy </li></ul><ul><li>  </li></ul><ul><li>Random...
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ECCLU 2011 - C. Parker - Controversy: Locally advanced prostate cancer - Pro radiation

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  • Biochemical progression-free survival of all patients with undetectable prostate-specific antigen after radical prostatectomy (intention-to-treat group 2 [ITT2]).
  • Brain Site Committee -- Dr. Warren Mason 26 February 2008 NCIC Clinical Trials Group -- NCI US Site Review Brain Site Committee -- Dr. Warren Mason 26 February 2008 NCIC Clinical Trials Group -- NCI US Site Review
  • ECCLU 2011 - C. Parker - Controversy: Locally advanced prostate cancer - Pro radiation

    1. 1. Locally advanced prostate cancer: pro radiation Chris Parker Change Presentation title and date in Footer dd.mm.yyyy
    2. 2. Locally advanced prostate cancer <ul><li>Randomised trials of hormone therapy </li></ul><ul><li>  </li></ul><ul><li>Randomised trials of post-op radiotherapy </li></ul><ul><li>  </li></ul><ul><li>Randomised trials of radiotherapy </li></ul><ul><li>Randomised trials of surgery </li></ul>
    3. 3. Prostate cancer specific mortality
    4. 4. Overall mortality
    5. 5. Locally advanced prostate cancer <ul><li>Randomised trials of hormone therapy </li></ul><ul><li>  </li></ul><ul><li>Randomised trials of post-op radiotherapy </li></ul><ul><li>  </li></ul><ul><li>Randomised trials of radiotherapy </li></ul><ul><li>Randomised trials of surgery </li></ul>Early hormone therapy is a standard of care
    6. 6.
    7. 7. bPFS
    8. 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
    9. 9.
    10. 10. Locally advanced prostate cancer <ul><li>Randomised trials of hormone therapy </li></ul><ul><li>  </li></ul><ul><li>Randomised trials of post-op radiotherapy </li></ul><ul><li>  </li></ul><ul><li>Randomised trials of radiotherapy </li></ul><ul><li>Randomised trials of surgery </li></ul>Early hormone therapy is a standard of care Local recurrence rate after surgery = 25% (or more)
    11. 11. <ul><ul><li>1996-2002 </li></ul></ul><ul><ul><li>875 patients </li></ul></ul><ul><ul><ul><li>median age 66 years </li></ul></ul></ul><ul><ul><ul><li>median PSA 16 ng/ml </li></ul></ul></ul><ul><ul><ul><li>78% T3 </li></ul></ul></ul><ul><ul><ul><li>N0, M0 </li></ul></ul></ul><ul><ul><li>MAB for 3 months, then flutamide alone +/- RT to prostate (70Gy) and seminal vesicles (50Gy) with a 2cm margin </li></ul></ul>Widmark et al. Lancet (2009)
    12. 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. 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. 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. 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. 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. 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. 18. Treatment <ul><li>Radiotherapy </li></ul><ul><ul><li>45 Gy/25 F/5 weeks to pelvis </li></ul></ul><ul><ul><li>20-24 Gy/10-12 F/2-2.5 weeks to prostate </li></ul></ul><ul><ul><li>If treating physician felt patient inappropriate for whole pelvis then RT given to prostate only </li></ul></ul>
    19. 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. 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. 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. 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. 23. Radiotherapy is getting better!
    24. 24. Locally advanced prostate cancer <ul><li>Randomised trials of hormone therapy </li></ul><ul><li>  </li></ul><ul><li>Randomised trials of post-op radiotherapy </li></ul><ul><li>  </li></ul><ul><li>Randomised trials of radiotherapy </li></ul><ul><li>Randomised trials of surgery </li></ul>Early hormone therapy is a standard of care Local recurrence rate after surgery = 25% (or more) Radiotherapy halves prostate cancer specific mortality
    25. 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. 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. 27. Locally advanced prostate cancer <ul><li>Randomised trials of hormone therapy </li></ul><ul><li>  </li></ul><ul><li>Randomised trials of post-op radiotherapy </li></ul><ul><li>  </li></ul><ul><li>Randomised trials of radiotherapy </li></ul><ul><li>Randomised trials of surgery </li></ul>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

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