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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
LDR Prostate Brachytherapy Results
Series Year No Follow-up Results
PottersJUrol 2005
2005 1449 12yr 81% OS
93% DFS
Stock and StoneInt J Radiat Oncol Biol Phys 2006
2006 1561Various treatment combinations
All risk groups
10 yr 74% OS
96% DFS
SylvesterInt J Radiat Oncol Biol Phys 2003
2003 232EBRT + BXT
10 yr 70% BRFSLow - 85%
Int - 77%
High – 57%
GrimmInt J Radiat Oncol Biol Phys 2001
2001 125Monotherapy
Low risk
10 yr 87% 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: 24
0.2
30m
0.8
36m
1.2
42m
1.8
48m
2.6
54m
4.7
60m
ASTRO definition
33m
Radical Radical ProstatectomyProstatectomy failurefailure
3636mm
Houston +2Houston +2
51m51m
Guildford: Patient Characteristics
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
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 SurvivalSurvival Plot
0 10 20 30 40 50 60 70 80 90 100Time
0.0
0.2
0.4
0.6
0.8
1.0S
urv
ivo
r F
un
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92% 5-year PSA RFS
5-year Biochemical RFS by Risk GroupSurvival Plot
0 10 20 30 40 50 60 70 80 90 100Time
0.0
0.2
0.4
0.6
0.8
1.0S
urvi
vor
Fun
c tio
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210
SPI
Low 95%
Intermediate 88%
High 90%
Low-Risk GroupSurvival Plot
0 10 20 30 40 50 60 70 80 90 100Time
0.0
0.2
0.4
0.6
0.8
1.0
Su
rviv
or
Fu
nct
ion
Survival Plot
0 10 20 30 40 50 60 70 80 90 100Time
0.0
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0.4
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Su
rviv
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98%91%
BXT Alone NAAD + BXT
Intermediate-Risk GroupSurvival Plot
0 10 20 30 40 50 60 70 80 90 100Time
0.0
0.2
0.4
0.6
0.8
1.0
Su
rviv
or
Fu
nct
ion BXT 89%
Survival Plot
0 10 20 30 40 50 60 70 80 90 100Time
0.0
0.2
0.4
0.6
0.8
1.0
Su
rviv
or
Fu
nct
ion NAAD + BXT
87%
Survival Plot
0 10 20 30 40 50 60 70 80 90 100Time
0.0
0.2
0.4
0.6
0.8
1.0
Su
rviv
or
Fu
nct
ion EBRT + BXT
80%
Survival Plot
0 10 20 30 40 50 60 70 80 90 100Time
0.0
0.2
0.4
0.6
0.8
1.0
Su
rviv
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NAAD, EBRT + BXT 92%
High-Risk Group
Survival Plot
0 10 20 30 40 50 60 70 80 90Time
0.0
0.2
0.4
0.6
0.8
1.0
Su
rviv
or
Fu
nct
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NAAD + BXTSurvival Plot
0 10 20 30 40 50 60 70 80 90Time
0.0
0.2
0.4
0.6
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1.0
Su
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Fu
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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 69T2b, GS 8, PSA 9.8 NAAD, EBRT + BXT Failed at 10 months, died at 4 years
• Age 61T2c, 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
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