Hormone treatment combined with radiotherapy Oncology 12

Hormones + Radiotherapy – Locally Advanced Prostate Cancer – T3/T4 Versus Plus Hormone Therapy

Traditionally, single modality treatment for locally advanced and high risk prostate cancer patients results in high failure rate

Hormones + Radiotherapy – Locally Advanced Prostate Cancer – T3/T4 Neoadjuvant Cytoreductive Potentiating Effect ? Apoptosis Adjuvant Eliminate Micrometastasis Neoadjuvant + Adjuvant ALL

Hormones + Radiotherapy – Locally Advanced Prostate Cancer – T3/T4 RTOG 86-10 – Roach -2008 (Pilepich 1995, 2001) RTOG 85-31- Pilepich Study – 2005 (1997, 2001) EORTC - Bolla Study – 2010. (Lancet 2002, 1997) RTOG 92-02 .

Short Term Neoadjuvant + Radiotherapy RTOG 86-10 Overall survival 471 Patients -Bulky T2-T4 Tumours 70% T3-T4 and Gleason 7-10 Hormones – 2months before and during RT Hormones for 4 months approx Roach, M. et al. J Clin Oncol; 26:585-591 2008

Short Term Neoadjuvant + Radiotherapy RTOG 86-10 Overall survival No Impact on Overall Survival Disease Specific mortality – P = .01 at 10 yrs Disease Free Survival P < .0001 10 year DSM 23% vs 36% 10 yr Disease free survival 11% vs 3% No increased risk of fatal cardiac events Roach, M. et al. J Clin Oncol; 26:585-591 2008

Hormones + Radiotherapy – Locally Advanced Prostate Cancer – T3/T4 Neoadjuvant No improvement in Overall Survival. . May be Adequate in subset – T3 and Gl Score 2-6 Adjuvant Concurrent + Adjuvant

Adjuvant + Radiotherapy RTOG 85-31 Overall survival 977 Patients – Non - Bulky T3N+ 71% Gleason Score 7-10 & 29% Node + Hormones Last week of RT + Indefinitely Pilepich et al. Int J Rad Oncol Biol Phys 2005; 61:1285

Adjuvant + Radiotherapy RTOG 85-31 Overall survival Overall Survival Significantly Greater Disease Specific Survival – P=.005 @ 10yrs Preferential Effect in Gleason Score 7-10 10 year OS 49% vs 39%(p=0.002) 10 year DSS 24% vs 39% (p<0.001) Pilepich et al. Int J Rad Oncol Biol Phys 2005; 61:1285

Hormones + Radiotherapy – Locally Advanced Prostate Cancer – T3/T4 Neoadjuvant No improvement in overall Survival. May be Adequate in subset – T3 and Gl Score 2-6 Adjuvant Improved Overall Survival. Most Benefit seen in Gl Score 7-10 Concurrent + Adjuvant

Concurrent + Adjuvant + Radiotherapy EORTC 22863 Bolla Study – 415 Patients 91% T3-4 & >30% Grade 3 (or Gl Score 7-10) Hormones First week of RT + 3 years RCT Radiotherapy 50Gy pelvis. Additional 20Gy prostate Bolla M et al. Int J Rad Oncol Bio Phys 2008;72 Bolla M et al. Lancet 2010

Concurrent + Adjuvant + Radiotherapy EORTC 22863 10 yr Overall Survival -  by ~20% 10 yr Disease Specific Survival  by 20% Cardiovascular Mortality Not Different Bolla M et al. Int J Rad Oncol Bio Phys 2008;72 Bolla M et al. Lancet 2010

Hormones + Radiotherapy – Locally Advanced Prostate Cancer – T3/T4 Neoadjuvant No improvement in overall Survival. May be Adequate in subset – T3 and Gl Score 2-6 Adjuvant Improved Overall Survival. Most Benefit seen in Gl Score 7-10 Concurrent + Adjuvant Survival Benefits in all Risk Groups Neoadj + Adjuvant

Neoadjuvant + Adjuvant + Radiotherapy RTOG 92-02 Overall survival No Impact on Overall Survival at 5 yrs Disease Specific Survival – P = .003 at 5 yrs Overall survival and Disease Free Survival P < .0001 Gl score 8-10 Benefit Disease Free Survival Hanks GE et al. J Clin Oncol 2008; 21:3972

Hormones + Radiotherapy – Locally Advanced Prostate Cancer – T3/T4 Neoadjuvant No improvement in overall Survival. May be Adequate in subset – T3 and Gl Score 2-6 Adjuvant Improved Overall Survival. Most Benefit seen in Gl Score 7-10 Concurrent + Adjuvant Survival Benefits in all Risk Groups Neoadj + Adjuvant Overall and Disease Specific Survival in Gl Score 8-10

Hormones + Radiotherapy – Locally Advanced Prostate Cancer – T3/T4 What Should be the Duration of Hormone Therapy?

Duration of Hormone Treatment Overall Survival 6 Months vs 3 Years Long–Term Suppression – 3 Years Significantly Better - Overall Survival - Cancer Specific Survival No Difference in Fatal Cardiac Events Cardiac Event Mortality Approx 1000 pts 5 yr Overall mortality for short term hormones 19% vs 15% Bolla M et al. NEJM 2009;360:2516

Duration of Hormone Treatment Insomnia Hot Flashes Long Term Androgen Suppression Significant worsening of Insomnia Hot Flushes Sexual Interest Sexual Activity But not Overall Quality of Life Decreased Libido Sexual Activity Quality of Life Bolla M et al. NEJM 2009;360:2516

EAU Guidelines 2014 minimum dose of > 74 Gy is recommended for EBRT + hormone therapy