1. Prostate Support Group Dr Duncan McLaren Consultant Oncologist

2. Presentation Radiotherapy results Current RT dose IGRT IMRT- Rapid arc HDR Q&A session New Drugs Q&A

3. Some good news Improved cause specific survival with radiotherapy over the last 30 years 2001-6 1996-01 1982-92 35% 70% 80%

4. Some good news 2001-6 1996-01 1982-92 50Gy 52.5Gy 55Gy

5. Effect of dose escalation 55Gy 52.5Gy P=0.0086 Time to PSA relapse years 80% 60% T1-2b Gleason 6 PSA<10

6. 55Gy 52.5Gy Time to PSA relapse Years P<0.0001 70% 40% T2c or Gleason 7 or PSA >10

7. P = 0.0086 55Gy 52.5Gy Time to PSA relapse Years P<0.0001 40% 20% T3 or PSA >20 or Gleason grade >8

8. ALPHA BETA DOSE per fraction SF Alpha/Beta for tumour = 10 Alpha/Beta for prostate tumour =1.5-3.0 Alpha/Beta for normal tissue = 5 Prostate Tumour Normal tissue 2Gy per day 3Gy per day Why dose such a modest dose escalation work ! 2 34

9. Advantages of Hypo-fractionation Shorter number of treatments –Benefits patients and machine capacity Possible reduced acute toxicity –CHHiP toxicity data supports this Possible improved efficacy –CHHiP outcome data awaited –In house data very supportive

10. Potential disadvantages If alpha beta ratio is wrong then a lower dose is given It may increase late damage on the rectum or bowel –No evidence of this with in house data Need to deliver dose very accurately IGRT conformal XRT or IMRT

11. Current XRT schedules Hypo-fractionation 57Gy in 19# 3Gy per day 74Gy equivalent 60Gy in 20# future dose 78Gy equivalent Standard fractionation 74Gy in 37# 2Gy per day Can treat pelvic nodes Future dose 78Gy

12. Image Guided Radiotherapy IGRT 2009 Fiducial Markers Inserted trans rectally Images true prostate position and software calculates how much to move the field to correct for it Why we can increase our doses safely

13. Advantages over conformal XRT Much tighter dose to the prostate Reduced dose to normal tissue Further dose escalation Disadvantages Prostate movement Time consuming Irradiated volume Intensity modulated radiotherapy IMRT

14. New for 2012! Even better XRT! Varian Novalis Trilogy Linear Accelerator with Rapid Arc

15. Faster, reduced dose to normal tissues, greater patient throughput and can be used as a standard linear accelerator

16. 2012 research project to use Multi-parametric MRI to fuse with planning CT scan to allow potential prostate tumour boost dose

17. What is happening in Prostate Brachytherapy? Low dose rate Permanent Iodine 125 seeds High dose rate Temporary Iridium 192

18. Single stop intraoperative prostate Seeds Brachytherapy Live since 2010

19. First 150 men @ 5yrs P=0.0005 95% 80% 55% poor Int good

20. 5 year outcomes 5 yr PSA RFS 52.5Gy55GyBrachy57-60Gy verses 74Gy GOOD 60%80%95%? INT 40%70%80%? POOR 20%40%55%?

21. How to improve outcome for high risk disease Single fraction of HDR brachytherapy and 13 fractions of external beam External beam Brachytherapy

22. HDR High dose rate prostate brachytherapy Business case 2012

23. Advantages Very high dose boost single 15Gy fraction Flexibility to ensure dose constraints to rectum and urethra are met by adjusting catheter or source position Reduced irradiated volume 13 fractions of XRT 2 weeks later 2 Gy equivalent dose >100Gy Disadvantages Relatively medically labour intensive GA or spinal Possible overnight stay

24. New drugs in metastatic prostate cancer

25. How does hormone blockade work? ZOLADEX CASODEX

26. LHRH agonists

27. Degarelix – GnRH antagonist 240mg given as 2 subcutaneous injections of 120mg each (loading) Followed by 80mg maintenance every 28 days

28. Degarelix - Firmagon SMC approval for advanced prostate cancer January 2011 Locally used for high risk patients with high PSA and very symptomatic e.g. SCC Major benefit is lack of testosterone flare

29. Abiraterone mode of action - Cyp -17 blocker Blocks intra- tumour androgens Blocks body androgens

30. Abiraterone 14.8 mths OS Placebo 10.9 mths OS Abiraterone Phase III trial results HR 0.65 Median Survival benefit = 3.9 months

31. MDV 3100 AFFIRM Trial Androgen receptor signalling blocker Results not yet published but trial closed December 2011 OS 18.4 months MDV 3100 OS 13.6 months placebo HR 0.63 Median survival benefit 4.8 months

32. Alpharadin- Radium 223 ALYMPSA Trial post Taxotere progression 16.3 mths 11.5mths Median survival benefit 4.8 months

33. Cabazitaxel v Mitoxantrone post Taxotere progression- TROPIC Trial Median survival 15.1 mths Cabazitaxel v 12.7 mths Mitoxantrone p=0.04 positive results does not = NHS funding Median survival benefit 2.4 months

34. Thank you