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

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

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

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

Sylvester et al, IJROBP 2007

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%

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

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

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

Definitions of failure post BXT PSA: 0.2 Time: m m m m m m ASTRO definition 33m Radical Prostatectomy failure 36 m Houston +2 51m

Guildford: Patient Characteristics Median follow-up 72 months (38-96) Mean age 68 years (44-76) PSA >204 GS StageT1c172 T2 a/b149 T2c66 T3a13 RiskLow197 Intermediate144 High59

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

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