1. Jan J Battermann & the UMC-Utrecht brachyteam The Truth On Permanent Prostate Brachytherapy

4. Current Perineal Technique at UMC-Utrecht - perineal procedure - US guided/MR fusion - stepping unit, rotating motor - free seeds/strands - intra-operative planning - activity 0.4 - 0.5 mCi - minimum dose 144 Gy

7. D90: Intraoperative versus 4 weeks postimplant Patients n Diff-D90 (SD) p-value All 389 -22 Gy (27) <0.0001 Rapid Strands (RS) 67 -39 Gy (28) <0.0001 InterSource Strands (IS) 136 -27 Gy (28) <0.0001 SelectSeeds (SS) 186 -13 Gy (22) <0.0001 Moerland 2009

9. Strands versus loose seeds, bNED UMC Utrecht data, I-125, 144 Gy, 1989-2004 Hinnen 2010

14. Biochemical no evidence of disease Cumulative Biochemical Failure Freedom

15. Disease Specific Survival

16. Overall Survival

17. Results of PPB monotherapy: low risk patients author #pat ADT f-up bNED DSS OS % mths 5y 10y 5y 10y 5y 10y ————————————————————————————————— Cosset 2008 533 53 43 97 98 Morris 2009 586 44 54 96 95 Taira 2010 319 0 74 96 100 76 Hinnen 2010 232 15 69 88 96 68 ** monotherapy +/- EBRT, multicentre analysis *** multicentre analysis, 8 year results

18. Results of PPB monotherapy: intermediate risk patients author #pat ADT f-up bNED DSS OS % mths 5 10y 5y 10y 5y 10y ————————————————————————————————— Cosset 2008 276 68 43 94 98 Morris 2009* 419 100 54 96 95 Taira 2010 144 0 74 96 100 74 Hinnen 2010 369 18 69 61 82 59 * only PSA 10-15,Gl-6 or Gl-7 with PSA <10

19. Results of PPB monotherapy: high risk patients author #pat median bNED DSS OS f-up mth 5 10y 5y 10y 5y 10y ————————————————————————————————— Beyer 2003 1141 49 76 65 38 87 98 84 Hinnen 2010 320 69 30 69 49 ** monotherapy +/- EBRT, multicentre analysis *** multicentre analysis, 8 year results

23. Better results with prostatectomy? -> some results of PPB from literature author #pat median bNED OS DSS f-up mths 5 10y 5y 10y LR MR HR ————————————————————————————————— Beyer 2003 1141 49 76 65 38 87 98 84 69 Stone 2005* 279 60 91 Stone 2007** 2292 42.5 64 64 58 Zelefsky, 2007*** 1831 63 74 61 39 UMC series, 2010 936 69 79 57 67.5 96 87 69 * ADT for other purposes than volume downsizing ** monotherapy +/- EBRT, multicentre analysis *** multicentre analysis, 8 year results

25. PPB versus RP and EBRT, 5 year bNED results author #pat risk group % RP / PPB / EBRT low intermediate high —————————————————————————— ——————— Colberg 2007* 391 350 93 / 92 70 / 70 50 / 52 Pickles 2010** 139 139 94 / 88 100 / 78 Jabbari 2010*** 249 124 94 / 78 * single institution ** single institution matched pairs *** matched pairs

26. PPB versus 3D-CRT and CPBRT boost Jabbari 2010 249 patients treated with PPB and the outcomes were compared with 3D-CRT and CPBRT boost. With a median f-up of 5.3 years, bNED rate with PPB was 93% versus 78% for 3D-CRT and 91% for proton boost. A greater proportion of PPB patients achieved a lower PSA nadir compared with those after CPBRT (PSA nadir ≤0.5 ng/ml, 91% versus 59%, resp.). Mendenhall 2010 Early results of 3 dose escalation studies with proton therapy suggest high efficacy and minimal toxicity with only 1.9% Grade 3 GU symptoms and <0.5% Grade 3 GI toxicity.

28. Preliminary results from Netherlands Cancer Institute, BT versus RALP Low risk : <cT3 PSA<10ng/ml Gleason sum score <7

29. Do patients ≤60 need prostatectomy? author bNED ≤60 bNED >60 LR MR HR LR MR HR ———————————————————————————————— Merrick 2006* 96 100 Shapiro 2009** 91 80 70 92 83 72 Burri 2010*** (92) (87) Hinnen 2011**** (63) (46) * 8 year results ** 10 year results *** 8 year results, all risk groups **** 10 year results

30. Does age make a difference? - nYounger age equals better outcome due to lower risk-stages - No difference in outcome when adjusted for differences in risk group Hinnen 2010 NB: in 145 consecutive men over 75 after PPB only 1 patient died of prostate cancer (Merrick 2008)

32. Late toxicity and quality of life Author Conclusions Ferrer, Comparison of QoL at 2 years after prostatectomy, 2008 3D EBRT and PPB. Surgery had considerable negative effect on sexual function and continence. EBRT had a moderate effect on bowel and small on sexual function. PPB had only a moderate increase in urinary irritation. Malcolm, Comparison of QoL at 2 years after open and 2010 robotic surgery, cryoablation and PPB. PPB was associated with higher urinary function, bother scores and sexual function. Roeloffzen, Quality of life six years after permanent prostate 2010 brachytherapy was similar to base line.

33. Risk of SPC after radiotherapy Author Conclusions Baxter 2005 Increase of rectal cancer after prostate EBRT Bhojani 2010 No increase in SPC after radiotherapy own series RP and PPB showed at 5 years no difference in SPC (resp. 12.4% vs 11.5%), but (although small) patients <60 had a significant risk of bladder cancer Singh 2010 The SEER registry found the same after EBRT Cosset 2004 T he Commission on Radiological Protection considers the risk of SPCs after PPB negligible

34. S alvage treatment is only possible with significantly increased toxicity Moman 2010 Results of PPB in 31 patients after previous radiotherapy are limited and related to the initial risk status. Only low-risk patients with a long interval have a chance for long survival. bNED at 1 year 51% and at 5 year 20%. Grade 2 and 3 toxicity was 58% and 3%, resp. T2 weighted and DCE MRI guided focal therapy may lead to less toxicity. Burri 2010 In 37 men with median f-up of 86 months, salvage BT was associated with a 10-year bNED of 54% and cause-specific survival of 94%. Improved bNED was associated with pre-salvage PSA <6 ng/ml .

35. Local recurrence on MRI: high perfusion T2w-MRI DCE-MRI