1. Hormone treatment combined with radiotherapy
Oncology 12

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

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

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

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

6. 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:

7. 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:

8. 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

9. 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

10. Adjuvant + Radiotherapy RTOG 85-31
Overall survival
Overall Survival Significantly Greater
Disease Specific Survival – 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

11. 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

12. 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

13. 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

14. 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

15. 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 < Gl score 8-10 Benefit
Disease Free Survival
Hanks GE et al. J Clin Oncol 2008; 21:3972

16. 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

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

18. 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

19. 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

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