1. Updated 5-year Biochemical Relapse-Free Survival after Prostate Brachytherapy Jenny P. Nobes St. Luke’s Cancer Centre, The Royal Surrey County Hospital, Guildford

2. Introduction I 125 LDR interstitial prostate brachytherapy BRFS rates from USA equivalent to RP and conformal EBRT Different toxicity profile Monotherapy or combined modality NICE guidelines - continued audit and careful clinical governance recommended Kupelian et al, IJROBP 2004

3. Patient Selection T1 or T2 PSA <10 Gleason 3+3, or low volume 3+4 Prostate volume <50cc No prior TURP Minimal urinary symptoms: IPSS <15 Qmax >15 ml/sec

4. LDR Prostate Brachytherapy Results SeriesYearNoFollow-upResults Potters JUrol 2005 2005144912yr81% OS 93% DFS Stock and Stone Int J Radiat Oncol Biol Phys 2006 20061561 Various treatment combinations All risk groups 10 yr74% OS 96% DFS Sylvester Int J Radiat Oncol Biol Phys 2003 2003232 EBRT + BXT 10 yr70% BRFS Low - 85% Int - 77% High – 57% Grimm Int J Radiat Oncol Biol Phys 2001 2001 125 Monotherapy Low risk 10 yr87% BRFS

5. Sylvester et al, IJROBP 2007

6. Guildford Results Khaksar et al, BJUi 2006 First 300 patients 5 year actuarial PSA relapse-free survival - 93% Low risk - 96% Intermediate risk - 89% High risk - 93%

7. Guildford: Updated Study 1007 patients treated to date First 400 patients treated March 1999-Dec 2003 Prospective database Patients stratified by risk group and treatment received –Brachytherapy (BXT) 145Gy alone –Neo-adjuvant androgen deprivation (NAAD) + BXT –External beam radiotherapy (EBRT) 45Gy + 110Gy BXT –NAAD, EBRT + BXT Assessment of BRFS, PSA nadirs and toxicity

8. Risk Classification MSKCC risk groupings Gleason score >6 PSA >10 Clinical stage >T2b 0 = Low risk 1 = Intermediate risk 2 or 3 = High risk Zelefsky et al, J Urol 2001

9. Definitions of Biochemical Failure ASTRO definition – 3 consecutive PSA rises –Sensitivity 51% –Specificity 81% Modifed ASTRO – 2 consecutive PSA rises ‘Houston’ – PSA nadir + 2ng/ml –Sensitivity 72% –Specificity 83% –Best surrogate for failure after BXT or EBRT Kuban et al, IJROBP 2006

10. Definitions of failure post BXT PSA: 0.2 Time: 24 0.2 30 m 0.8 36 m 1.2 42 m 1.8 48 m 2.6 54 m 4.7 60 m ASTRO definition 33m Radical Prostatectomy failure 36 m Houston +2 51m

11. Guildford: Patient Characteristics Median follow-up 72 months (38-96) Mean age 68 years (44-76) PSA 0-421 4.1-10269 10.1-20106 >204 GS 0-458 5-6270 7-1072 StageT1c172 T2 a/b149 T2c66 T3a13 RiskLow197 Intermediate144 High59

12. Treatment Received BXT 167 (42%) NAAD + BXT155 (39%) EBRT + BXT12 (3%) NAAD, EBRT + BXT64 (16%)

13. Low-Risk Group n = 197 (49%) BXT alone 122 NAAD + BXT72 EBRT + BXT0 NAAD, EBRT + BXT3

14. Intermediate-Risk Group n = 144 (36%) BXT alone 38 NAAD + BXT75 EBRT + BXT5 NAAD, EBRT + BXT24

15. High Risk-Group n = 59 (15%) BXT alone 7 NAAD + BXT8 EBRT + BXT7 NAAD, EBRT + BXT37

16. Biochemical Failures - nadir + 2ng/ml n = 28/400 (7%) Risk Group Low9 Intermediate14 High5 Treatment BXT6 NAAD + BXT15 EBRT + BXT1 NAAD, EBRT + BXT6

17. 5-year Biochemical Relapse-Free Survival 92% 5-year PSA RFS

18. 5-year Biochemical RFS by Risk Group Low 95% Intermediate 88% High 90%

19. Low-Risk Group 98% 91% BXT AloneNAAD + BXT

20. Intermediate-Risk Group BXT 89% NAAD + BXT 87% EBRT + BXT 80% NAAD, EBRT + BXT 92%

21. High-Risk Group NAAD + BXTNAAD, EBRT + BXT 88%

22. PSA Nadirs 4 years- 228 values PSA≤ 0.583% (n=189) PSA≤ 0.257% (n=130) 5 years- 128 values PSA≤ 0.5 86% (n=110) PSA≤ 0.277% (n=98)

23. Deaths Total deaths = 11 Prostate cancer deaths = 2 Age 69 T2b, GS 8, PSA 9.8 NAAD, EBRT + BXT Failed at 10 months, died at 4 years Age 61 T2c, GS 5, PSA 6 BXT alone, Failed at 13 months, died at 4 years

24. Toxicity Urinary Acute retention7% (28) Urethral stricture 8% (32) TURP2.5% (10) Erectile dysfunction 226 (57%) potent at baseline (IIEF > 11) 71% remain potent at 2 years (60% with PDE-5i)

25. Summary Prospective UK results consistent with US data Well-tolerated radical treatment option Toxicity similar to published series ED likely to improve with technique modifications Post-implant CT-based dosimetry essential (D 90 ≥140Gy correlates with PSA control) Importance of continued local appraisal of dosimetry and outcomes

26. Acknowledgements Professor Stephen Langley Dr Robert Laing Dr Sara Khaksar Dr David Lovell Dr Julian Money-Kyrle Professor Ian Wells Mr Prasanna Sooriakumaran Mr Alistair Henderson