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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
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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 • I125 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
Guildford Results • First 300 patients • 5 year actuarial PSA relapse-free survival - 93% • Low risk - 96% • Intermediate risk - 89% • High risk - 93% Khaksar et al, BJUi 2006
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
ASTRO definition 0.8 36m 1.2 42m 1.8 48m PSA: 0.2 Time: 24 4.7 60m 0.2 30m 2.6 54m 36m 33m 51m Radical Prostatectomyfailure Houston +2 Definitions of failure post BXT
Median follow-up 72 months (38-96) Mean age 68 years (44-76) PSA 0-4 21 4.1-10 269 10.1-20 106 >20 4 GS 0-4 58 5-6 270 7-10 72 Stage T1c 172 T2 a/b 149 T2c 66 T3a 13 Risk Low 197 Intermediate 144 High 59 Guildford: Patient Characteristics
Treatment Received • BXT 167 (42%) • NAAD + BXT 155 (39%) • EBRT + BXT 12 (3%) • NAAD, EBRT + BXT 64 (16%)
Low-Risk Group • n = 197 (49%) • BXT alone 122 • NAAD + BXT 72 • EBRT + BXT 0 • NAAD, EBRT + BXT 3
Intermediate-Risk Group • n = 144 (36%) • BXT alone 38 • NAAD + BXT 75 • EBRT + BXT 5 • NAAD, EBRT + BXT 24
High Risk-Group • n = 59 (15%) • BXT alone 7 • NAAD + BXT 8 • EBRT + BXT 7 • NAAD, EBRT + BXT 37
Biochemical Failures - nadir + 2ng/ml • n = 28/400 (7%) Risk Group • Low 9 • Intermediate 14 • High 5 Treatment • BXT 6 • NAAD + BXT 15 • EBRT + BXT 1 • NAAD, EBRT + BXT 6
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 BXT Alone NAAD + BXT 98% 91%
Intermediate-Risk Group BXT 89% NAAD + BXT 87% NAAD, EBRT + BXT 92% EBRT + BXT 80%
High-Risk Group NAAD + BXT NAAD, EBRT + BXT 88% 88%
PSA Nadirs • 4 years - 228 values PSA ≤ 0.5 83% (n=189) PSA ≤ 0.2 57% (n=130) • 5 years - 128 values PSA ≤ 0.5 86% (n=110) PSA ≤ 0.2 77% (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 retention 7% (28) • Urethral stricture 8% (32) • TURP 2.5% (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 (D90≥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