1. RT for LocalisedProstate Cancer Alan Horwich Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, UK

3. MRI T2 Seminal vesicles - ve Nodes –veT2 N0 M0Management options 1. Surveillance Prostatectomy External Beam RT or Brachytherapy 2. Role of adjuvant hormone therapy

5. Gleason 9 (4+5), 9/9 cores ,

6. MRI =SV invasion bone scan –ve

7. T3b N0 M0Management options 1. Surveillance Prostatectomy External Beam RT or Brachytherapy 2. Role of adjuvant hormone therapy

8. Outline of Talk Why choose RT? Outcomes Current developments in external beam radiotherapy

9. Active surveillance as a treatment option Aim To select patients that will benefit from treatment. Who? Suitable for radical treatment Low volume cancer Low grade (gleason score 3+4=7) How? Regular PSA/clinical assessment Repeat biopsy MRI

10. Active surveillance is not watchful waiting

11. Early outcomes of active surveillance for localised prostate cancerHardie et al. BJU Int (2005) 95:956-60 Predictive factors Initial PSA F/T PSA(16%) PSA Density (0.18ng/ml/ml) PSA Velocity (Ing/ml/yr) (PSA DT) T Stage % core involvement Max. core involvement(20%) Outcome: treatment-free survival

12. Is there any evidence that one treatment is better than another? No randomised trials….

13. Outcome according to nomograms: Example: T1c,PSA 15.1 ng/ml, Gleason 7(3+4) Note: Nomograms have 10% error Radical Prostatectomy ~50% salvage by RT

14. --Estimated prostate-specific antigen outcome for low-risk patients stratified by treatment modality D'Amico, A. V. et al. JAMA 1998;280:969-974. Copyright restrictions may apply.

15. Disadvantages of treatments Radical Prostatectomy Sexual function Incontinence Major surgery Incomplete resection Brachytherapy Urinary dysfunction Surgical procedure Radical Radiotherapy Length of treatment Bowel dysfunction Sexual dysfunction(<RP) [second malignancy]

16. Ferrer et al IJROBP 72 p421-32 2008 Updated; Pardo et al 2010 JCO 28 p4687-95 Longutidinal study of 614 patients Black line: Rad Prostectomy, Dotted line: Brachy therapy , Grey line: EBRT

17. Improving Radiotherapy Dose matters..

18. Phase III randomised controlled trials of dose escalation in prostate cancer: PSA control

19. Phase III randomised controlled trials of dose escalation in prostate cancer: PSA control

20. Achieving radiotherapy dose escalation without increasing toxicity Minimising normal tissue irradiation Intensity Modulated Radiotherapy Image guided radiotherapy

21. Inverse Plan

22. Achieving radiotherapy dose escalation without increasing toxicity Minimising normal tissue irradiation Intensity Modulated Radiotherapy Image guided radiotherapy

23. Full rectum Empty rectum Prostate movements

24. IGRT : Gold grain fiducial markers

25. On line correction with intrafraction motion McNair IJROBP 2008 71(1) 41-50 Right- Left 3mm Ant-Post 3.6mm Sup-Inf 3.4mm

26. Achieving radiotherapy dose escalation without increasing toxicity Minimising normal tissue irradiation Intensity Modulated Radiotherapy Image guided radiotherapy Maximising therapeutic ration Hypo-fractionation

27. Achieving radiotherapy dose escalation without increasing toxicity Minimising normal tissue irradiation Intensity Modulated Radiotherapy Image guided radiotherapy Maximising therapeutic ration Hypo-fractionation Tumour boosting Intra-prostatic boost ‘stereotactic radiotherapy’

28. Singh Rad Oncol 2007 2 1-6 DCE MRI , guided biopsy and planning scan with fiducials N=4 75.6Gy (42 F) to prostate 94.5 Gy to 2subtargets

29. Achieving radiotherapy dose escalation without increasing toxicity Minimising normal tissue irradiation Intensity Modulated Radiotherapy Image guided radiotherapy Maximising therapeutic ration Hypofractionation Tumour boosting Intra-prostatic boost ‘stereotactic radiotherapy’ Prediction – treatment individualisation

30. A predictive marker for benefit of Dose Escalation ? Osteopontin Expression Patients treated at RMH in phase 3 trials of dose escalation Morgan NCIC Conf 2009 64Gy 74Gy 74Gy 64Gy HR 1.41 (0.53-3.76) P = 0.49 HR 0.42 (0.26-0.7) p = 0.001

31. Summary Organ confined prostate cancer has a good prognosis independent of primary treatment option Active surveillance is a reasonable option for many patients For those with higher risk of progression or wishing treatment there is no good evidence that any option is superior (in terms of survival) than any other. Choice may be made on consideration of efficiency, toxicities and patient preference.