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

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92% 5-year PSA RFS

5-year Biochemical RFS by Risk GroupSurvival Plot

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Low 95%

Intermediate 88%

High 90%

Low-Risk GroupSurvival Plot

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98%91%

BXT Alone NAAD + BXT

Intermediate-Risk GroupSurvival Plot

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Survival Plot

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87%

Survival Plot

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80%

Survival Plot

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NAAD, EBRT + BXT 92%

High-Risk Group

Survival Plot

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NAAD + BXTSurvival Plot

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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