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Title: Minimally invasive ablation therapies for localised prostate cancer is this the way forward


1
Minimally invasive ablation therapies for
localised prostate cancer -is this the way
forward?
  • Mark Emberton
  • Institute of Urology University College
    LondonLondon

2
Harms benefit ratio
  • Most men with localised prostate cancer are
    eligible for a range of therapies
  • active surveillance
  • radical surgery or radiotherapy
  • Most men struggle to make a decision
  • Both options are not entirely satisfactory

3
Estimate of benefit
  • 10 year follow-up watchful waiting versus radical
    prostatectomy
  • Prostate cancer specific deaths
  • Watchful waiting 14
  • Radical prostatectomy 9

Bill-Axelsen A, Holmberg L, Mirrja Ruuth et al.
NEJM 2005352 1977-1984.
4
Estimate of harm
  • Acute and chronic toxicity of therapies will
    impact on the majority
  • Minority will experience benefit
  • Toxicities perhaps under estimated
  • Study design
  • Cognitive dissonance

5
5 year urinary and sexual outcomes after radical
prostatectomy
N1288
Penson et al. J Urol 2005 173 (4) suppl 451
6
The challenge for radical therapies
  • To increase the proportion of men who have the
    perfect result (3/3)
  • No evidence of disease
  • Good urinary function / control
  • Acceptable sexual function

7
Editorial Comment on minimally invasive therapies
(HIFU)
  • Criticises the heterogeneity of the sample
  • Absence of viable tumour cells in every patient
    treated..
  • Side-effect profile currently unacceptable..
  • Congratulate the authors

Fitzpatrick J. Urology 2002 59(3) 398-9
8
Tissue ablation technologies
  • Use thermal energy to create tissue destruction
  • Numerous technologies
  • Different states of
  • Evaluation
  • Diffusion
  • Degrees of invasiveness
  • Very poor evidence base

9
Tissue ablation technologies
  • Cryotherapy
  • HIFU
  • Photo-dynamic therapy
  • Radio frequency tumour ablation
  • Interstitial self-regulating rods

Gillett et al. Mayo Clin Proc. 2004 Dec 79 (12)
1547-1555
10
Tissue ablation technology - desirable attributes
Gillett et al. Mayo Clin Proc. 2004 Dec 79 (12)
1547-1555
11
Tissue ablation technologies
  • Cryotherapy
  • HIFU
  • Photo-dynamic therapy
  • Radio frequency tumour ablation
  • Interstitial self-regulating rods

Gillett et al. Mayo Clin Proc. 2004 Dec 79 (12)
1547-1555
12
Current Standard - Combined Ultrasound and
Temperature Monitoring
  • Overcomes the limitations of ultrasound
    monitoring alone
  • System-integrated thermocouples are placed
    surrounding the prostate gland
  • Target temperatures may be confirmed
  • Protection of surrounding sensitive structures,
    e.g.
  • rectal wall
  • external sphincter

13
Technological developments
  • 1st Generation (1960s-1990s)
  • Poured Liquid Nitrogen
  • Pumped Liquid Nitrogen
  • 2nd Generation (Mid 1990s)
  • JT effect based cryoprobes
  • Thawing capabilities
  • 3rd Generation (2000s)
  • Ultra-thin (17-gauge) CryoNeedles

14
Cryoablation published outcomes to date
  • Reflect a combination of early and contemporary
    cryoablation
  • Early series report solely patients treated
    using the early technique
  • Current combined series include both patients
    treated using early and contemporary techniques
  • Future series will include patients treated
    solely using contemporary technique

15
Combined series early and contemporary
cryoablation
  • Thomas Baker Cancer Center (TBCC)
  • Crittenton Prostate Center (CPC)
  • Cryosurgical Center of Southern California (CCSC)
  • Health Care Financing Administration Decision
    Pool CPC, CCSC, NEMC, UCSF, Urologic Inst. Of
    New Orleans

16
Combined Cryo Series Methods
Saliken JC JVIR 1999 10 199-208, Chinn DO AUAWS
1999, Lee F Urology 1999 54 135-40, Whyte JJ J
Urol 1999 162 1386-7.
17
Combined Cryo Series Biochemical Outcomes by
Risk Groups
18
Combined Cryo Series Complications
19
Cryotherapy - current series
  • 1994-2004
  • 249 cases, both primary and secondary
  • 1/3 low, 1/3 moderate, 1/3 high risk
  • Follow-up 4months to 10 years
  • 230 evaluable patients

Derrick et al. AUA San Antonio, 2005
20
Cryotherapy - current series
  • 64 NED using 0.5 ug/L threshold
  • Bladder contracture 9 men
  • TURP 21
  • Prostate abscess 2
  • Fistula 1
  • Incontinence 10
  • Impotence 90

Derrick et al. AUA San Antonio, 2005
21
Cryotherapy as a salvage intervention
22
The problem
  • 25 40 of men will experience biochemical
    progression following RP
  • Most will occur with no radiographic or physical
    evidence of disease
  • Left untreated 65 will develop metastases within
    10 years

23
Salvage therapy key questions
  • Is the disease
  • Localised ?
  • Disseminated ?
  • Both ?
  • What are the objectives of salvage therapy?

24
Salvage options
Androgen suppression can be applied throughout
25
Salvage therapies following radiation failure
  • 5 year PSA relapse-free rates following IMRT and
    3-D Conformal RT

Risk stratification by PSA, Gleason Grade,
Clinical stage.
Zelefsky MJ et al. J Urol 2001 166
876- Zelefsky MJ et al. Int J Rad Oncol Biol Phys
1998 41491- Fukunaga-Johnson N et al. Int J Rad
Oncol Biol Phys 1997 38 311-
26
Diagnosis of local recurrence following radiation
failure
  • Predictors of recurrence following radiation
    therapy

27
SALVAGE CRYOTHERAPY
  • De la Taille A et al. Urology 2000 55(1) 79
    84
  • 43 men
  • Izawa JI et al. J Clin Oncol 2002 20(11)
    2664-71
  • 131 men
  • Bahn DK, Lee F, Silverman et al. Clin Prostate
    Cancer 2003 2(2) 11-4
  • 59 men

28
Modern Cryobiology
1st Generation 2nd Generation 3rd Generation
  • More even temperature distribution

29
Salvage Cryotherapy following radiation therapy
the Columbia experience
  • 43 men, 1994 -1999, mean FU 22 months
  • Biopsy proven disease
  • Requirements
  • MRI no SV invasion
  • Pelvic lymphadenectomy - negative
  • Negative bone scans
  • Neo-adjuvant AS 3 months
  • Biochemical relapse free survival defined as PSA
    lt 0.1ug/L

De la Taille A et al. Urology 2000 55(1) 79 - 84
30
Salvage Cryotherapy following radiation therapy
the Columbia experience
  • Complications / morbidity
  • Incontinence 9
  • Obstruction 5
  • Stricture 5
  • Rectal pain 26
  • UTI 9
  • Scrotal oedema 12
  • Haematuria 5

De la Taille A et al. Urology 2000 55(1) 79 - 84
31
Salvage Cryotherapy following radiation therapy
the Columbia experience
  • 60 reached PSA of 0.1ug/L
  • Biochemical relapse free survival
  • 6 months 79
  • 12 months 66
  • Biochemical relapse free survival
  • Detectable PSA post cryo 30
  • Undetectable PSA post cryo 73

De la Taille A et al. Urology 2000 55(1) 79 - 84
32
Salvage Cryotherapy - contemporary series
  • 22 men, treated 2000-2004 (EBRT/Brachy)
  • Mean age 70
  • PSA range 1.2 to 14.6
  • Gleason score range 6-9
  • Prostate size range 12-50cc

Lam et al. (Charlestone) AUA San Antonio, 2005
33
Salvage Cryotherapy - contemporary series
  • 92 achieved PSA lt0.04 ug/L _at_ 3 months
  • Sloughing 5
  • Pain 5
  • Incontinence 18
  • Impotence 83

Lam et al. (UCLA) AUA San Antonio, 2005
34
Focal cryotherapy
  • 2000-2004
  • Unifocal disease (12 cores), N0 M0
  • 3 month scheduled review
  • Failure
  • ASTRO
  • PSA nadir gt1ug/L

Masson et al. (Columbia) AUA San Antonio, 2005
35
Focal cryotherapy
  • Results
  • 19/20 preserved genito-urinary function
  • 1/20 increase in IPSS
  • 1/20 decreased erectile functiuon
  • No incontinence / pain / fistulae
  • 1 patient had residual disease (9 biopsied)

Masson et al. (Columbia) AUA San Antonio, 2005
36
Conclusions (Cryotherapy)
  • Probable current standard for salvage
  • Has many desirable attributes for an ablation
    therapy
  • For primary whole gland treatment genito-urinary
    toxicity remains high
  • Minimal toxicity when used focally

37
Tissue ablation technologies
  • Cryotherapy
  • HIFU
  • Photo-dynamic therapy
  • Radio frequency tumour ablation
  • Interstitial self-regulating rods

Gillett et al. Mayo Clin Proc. 2004 Dec 79 (12)
1547-1555
38
Principles of High Intensity Focused Ultrasound
39
Principles Of High Intensity Focused Ultrasound
40
HIFU Therapy for Localised Prostate Cancer
41
HIFU Therapy for Localised Prostate Cancer
  • Treat whole gland
  • Avoid injury to adjacent structures
  • Rectal wall
  • Rhabdo-sphincter
  • Ureters
  • (Neurovascular bundles)
  • (Urethra)

42
HIFU Therapy for Localised Prostate Cancer
  • Treatment strategy
  • Simplest treatment is the Six Segment treatment
    approach

Segment 1
Segment 2
Anterior Segments 1 and 2
Segment 3
Segment 4
Middle Segments 3 and 4
Posterior Segments 5 and 6
Segment 6
Segment 5
43
HIFU Therapy for Localised Prostate Cancer
Treatment strategy - Segment One Anterior,
treating right to center in the transverse plane,
4.0cm fl transducer, initial power setting
44
HIFU Therapy for Localised Prostate Cancer
Treatment strategy - Segment Two Anterior,
treating left to center in the transverse plane,
4.0 cm fl transducer initial power setting
45
HIFU Therapy for Localised Prostate Cancer
Treatment strategy - Segment Three Middle,
treating right to center in the transverse plane,
4.0 cm fl transducer at reduced power setting
46
HIFU Therapy for Localised Prostate Cancer
Treatment strategy - Segment Four Middle,
treating left to center in the transverse plane,
4.0 cm fl transducer at reduced power setting
47
HIFU Therapy for Localised Prostate Cancer
Treatment strategy - Segment Five Posterior,
treating right to center in the transverse plane,
3.0 cm fl transducer, at reduced power setting
48
HIFU Therapy for Localised Prostate Cancer
Treatment strategy - Segment Six Posterior,
treating left to center in the transverse plane,
3.0 fl transducer at reduced power setting
49
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50
Case series 5 year experience
Describes the outcome of 146 men treated with
Ablatherm
  • Mean follow-up 22.5 months (range 4-62)
  • n 146
  • PSA lt 16
  • Stage T1-T2 N0 M0
  • Gleason 7 or less

Blana A et al. Urology. 2004 Feb63(2)297-300
51
HIFU Results cancer control
  • Mean PSA nadir 0.07 ng/ml (range 0-5.67)
  • PSA lt 0.5 83
  • PSA lt 1.0 92
  • Negative Biopsy 93.4
  • Freedom from biochemical progression 87

Blana A et al. Urology. 2004 Feb63(2)297-300
52
HIFU Results - Toxicity
  • Incontinence (grade I) 5.8 at last f/u
  • No grade II or III incontinence
  • Obstruction requiring TURP 11.7
  • Impotence 52.7 (of those potent at time of
    HIFU)
  • UTI (6),
  • Fistula 0.7

Blana A et al. Urology. 2004 Feb63(2)297-300
53
Japanese experience with Sonablate 500
  • Patient characteristics
  • N 30
  • PSA 10.815.83 ng/ml
  • Stage T1b-T2 N0 M0
  • Gleason 2-4 (30), 5-7 (67), 8-10 (3)
  • Mean follow-up 14.7 months (range 6-35)

Uchida T et al. Jap. J. Endourol. 2004
16108-114
54
Japanese experience with Sonablate 500
  • Cancer control
  • 97 Freedom from biochemical progression
  • Negative Biopsy 100

Uchida T et al. Jap. J. Endourol. 2004
16108-114
55
Japanese experience with Sonablate 500
  • Morbidity
  • Urinary incontinence 0
  • Obstruction requiring TURP 3
  • Impotence (questionnaire) 33
  • Rectal Fistula 3

Uchida T et al. Jap. J. Endourol. 2004
16108-114
56
Five year outcome comparisons
  • Biochemical Disease Free Survival

BDFS definitions do vary but are comparable
57
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58
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59
Where is HIFU going?
  • Prospective trials needed
  • Salvage
  • Hemi-ablation
  • Image directed therapy (focal ablation)
  • HIFU in high grade disease
  • HIFU as adjuvant treatment with systemic
    therapies

60
Where is HIFU going?
  • Prospective trials needed
  • Salvage
  • Hemi-ablation
  • Image directed therapy (focal ablation)
  • HIFU in high grade disease
  • HIFU as adjuvant treatment with systemic
    therapies

61
Multi-centre European Phase II study - Primary
Protocol
  • T1-T2
  • PSA lt 15
  • Gleason lt 8
  • Volume lt 40
  • Prospectively measure
  • Biochemical response
  • Potency (IIEF)
  • Flometry PVR
  • Voiding complaints (IPSS)
  • Incontinence (questionnaire)

62
Where else is HIFU going?
  • Prospective trials
  • Salvage
  • Hemi-ablation
  • Image directed therapy (focal ablation)
  • HIFU in high grade disease
  • HIFU as adjuvant treatment with systemic
    therapies

63
Salvage HIFU following EBRT
  • 71 men
  • Mean FU 15 months
  • 67 years /- 6 years, mean prostate vol 21 ccs
  • Mean PSA 7.7 /- 8.0
  • Histological confirmation
  • Gleason score 2-6 24
  • 7 13
  • 8-10 34

Gelet et al. Local recurrence of prostate cancer
after external beam radiation therapy early
experience of salvage therapy using HIFU. Urology
2004 63(4)625-9.
64
Salvage HIFU following EBRT
  • 57 (80) negative biopsies
  • 43 (61) PSA nadir lt 0.5ug/L
  • Biochemical relapse free survival 44 at last
    review

Gelet et al. Local recurrence of prostate cancer
after external beam radiation therapy early
experience of salvage therapy using HIFU. Urology
2004 63(4)625-9.
65
Salvage HIFU following EBRT
  • Rectal fistula rate 6 overall
  • No rectal injuries using reduced power
  • Urinary Incontinence requiring pads 7
  • Bladder neck stenosis 17

Gelet et al. Local recurrence of prostate cancer
after external beam radiation therapy early
experience of salvage therapy using HIFU. Urology
2004 63(4)625-9.
66
Can HIFU be used following seed brachytherapy?
Ralf Seip, Adam Wunderlich, Cory Miller,
Narendra T. Sanghvi Focus Surgery, Inc.,
Indianapolis, IN. David Shaeffer, Peter
Lawrence, Thomas A. Gardner, Michael O. Koch,
Liang Cheng Indiana University School of
Medicine, Indianapolis, IN.
67
Rationale
  • Salvage therapies following brachytherapy are
    limited
  • Brachytherapy failures are usually excluded from
    salvage trials
  • Seeds may impact HIFU energy delivery.

68
Seed Implantation under Ultrasound Guidance
Brachytherapy Seeds
Prostate
Rectal Cavity
Base
Apex
Sonablate500 Ultrasound Sector (Transverse)
Image Plane
69
Prostate X-Ray Images
70
Sonablate500 Prostate Treatment Setup
  • Sonablate500 HIFU System
  • SonachillTM Pump/Chiller Unit
  • Transrectal HIFU Probe 4.0 MHz, 40/30 mm Focal
    Length
  • Probe Arm
  • Stand-Alone Thermometry System
  • Animal held in Lithotomy Position
  • Cleansed Rectum/ free of Fecal Matter

Sonablate500
SonachillTM
Thermocouples
HIFU Probe
Probe Arm
71
Treatment Plan
72
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73
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74
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75
HIFU Treatment Parameters
The same treatment parameters as those used for
HIFU Prostate Cancer treatment in Humans were
used for this study
  • 4.0 MHz Therapy Probe, 40/30 mm Focal Length.
  • 0-37 W TAP for 40 mm Focal Length Probe.
  • 0-24 W TAP for 30 mm Focal Length Probe.
  • 3 seconds HIFU ON Time, 6 seconds HIFU OFF Time
    for each shot.
  • Entire Prostate Gland was treated.
  • Anterior to Posterior Treatment Sequence.

76
Prostate X-Ray Images
Apex
7
6
5
4
3
2
1
7 Sections, 5 mm spacing
Base
77
Prostate Histology
Prostate Section X-Ray Image
Paraffin Block Fix
HE Stained Slide
78
Prostate Histology
Rectal Lining
Approximate Seed Location
79
Conclusions
  • The presence of brachytherpay seeds do not appear
    to affect the HIFU lesion
  • No thermal damage to the rectal wall
  • Tissue destruction at the cellular level is
    similar to that seen in treatments performed
    without seeds
  • Thermometry measurements revealed intra-prostatic
    temperature elevations similar to those in HIFU
    treatments performed without seeds in humans

80
Summary Salvage Therapies
  • No evidence of disease (NED) rates and negative
    biopsy status

Heterogeneity in disease severity, comorbidity
and definition of failure
81
Where else is HIFU going?
  • Salvage
  • Hemi-ablation
  • Image directed therapy (focal ablation)
  • HIFU in high grade/stage disease
  • HIFU as adjuvant treatment with systemic
    therapies

82
Where else is HIFU going?
  • Salvage
  • Hemi-ablation
  • Image directed therapy (focal ablation)
  • HIFU in high grade/stage disease
  • HIFU as adjuvant treatment with systemic
    therapies

83
Where else is HIFU going?
  • Salvage
  • Hemi-ablation
  • Image directed therapy (focal ablation)
  • HIFU in high grade/stage disease
  • HIFU as adjuvant treatment with systemic
    therapies

84
Conclusions
  • Minimally invasive
  • Reliable technology
  • A surgical intervention
  • Technology in evolution
  • European initiative
  • Varied indications
  • Outcomes lack precision, but are likely to
    improve

85
Tissue ablation technologies
  • Cryotherapy
  • HIFU
  • Photo-dynamic therapy
  • Radio frequency tumour ablation
  • Interstitial self-regulating rods

Gillett et al. Mayo Clin Proc. 2004 Dec 79 (12)
1547-1555
86
Photodynamic

therapy
accumulation
application
therapy
laser
12

9
3
6
photosensitiser
87
PHOTODYNAMIC THERAPY (PDT)
88
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89
Aim of the Study
  • To assess the efficacy and the tolerability of
    WST-09 in men with untreated localized prostate
    cancer.
  • Objectives
  • To assess the PDT-induced lesions associated
    with escalating doses of light and a fixed dose
    of WST09 using MR imaging
  • To monitor the safety and tolerability of
    administering escalating doses of light using a
    fixed dose of WST09
  • To monitor cancer-specific outcomes such as PSA
    and TRUS-guided biopsy of the prostate in order
    to inform the design and conduct of future
    randomized controlled trials

90
Methodology
  • open, single centre, single arm, phase IIa
    study
  • single-dose administration of WST09 (2 mg/kg)
    combined with percutaneous transperineal
    interstitial
  • light delivery (50 to 360 J/cm)
  • total number of patients  34
  • duration of the study / patient  12 months

91
Trial Design
  • The trial is structured in 2 phases
  • Part A
  • - First data on safety and tolerability in
    untreated
  • human prostate tissue
  • - 2 fibres inserted in the prostate one in
    each lobe
  • - escalating light doses applied (50 to 360
    J/cm)
  • - fixed WST09 dose (2 mg/kg)
  • - inclusion of 14 patients (or more, if
    variability)

92
Trial Design Part B
  • Part B
  • - assessment of the feasibility and safety
    associated with the placement of multiple fibers
    in the two lobes of the prostate
  • fixed WST09 dose (2 mg/kg)
  • escalating number of fibers, in order to achieve
    ablation without extraprostatic damages
  • inclusion of 20 patients
  • ? efficacy measured by PSA, MRI and biopsy (opt.)

93
Study Visits
94
Needles in the prostate prior to light delivery
95
Transrectal ultrasound during PDT
96
Theatre staff, fibre placement and monitoring
equipment
97
Treatment plan TV section
Diffuser fibre (D)
L6
M1
M4
L3
Monitor fibre (M)
L1
L5
Catheter plus Monitor fibre
D2
M3
D1
M2
Stabiliser needle
L4
L2
98
Treatment plan - Sagital section
Diffuser fibre (D)
Monitor fibre (M)
2- 4 cm fibre
Catheter plus Monitor fibre
Stabiliser needle
L2
L1
Sphincter active area
99
Patients in study 2.13
  • 6 patients had PDT between December 2004 and May
    2005
  • Mean age 71 (range 59 -79)
  • Gleason 3 3 in most patients, 34 in 1 patient
  • Mean pre treatment PSA 9.7 (range 6.1 19.6)

100
Patient 0103
Pre PDT
1 week post PDT Necrosis 1.06 x 1.44 cm (axial
plane) 1.94 cm sagittal plane
2 mg/kg. 150 J/cm , 3 cm CD on right 100J/cm 2
cm CD on left
101
A
B
C
Patient 0106 Pre PDT (A) tumour not visble B 1
week post PDT, necrosis on right (7.1 cm3)(150
J/cm x 2cm) C 1 week post PDT, necrosis on left
(0.96 cm3)(150 J/cm x 1 cm)
102
  • Tookad 2.08 pat.03
  • 2 mg/kg 6 fibers x 360J/cm
  • Lesion 80 at day 7

103
Side effects
  • 2/6 superficial thrombosis in vein into which
    drug administered
  • 2/6 transient irritative symptoms (lt 2 weeks)
  • 3/6 transient asymptomatic changes in liver
    function
  • No effect on sexual function
  • 2/6 urinary symptoms much improved since PDT
  • Catheter out at 24 hours in all patients

104
Calculation of optical properties
  • Penetration depth depth at which 1/e or 63 of
    light lost
  • Inverse of effective attenuation coefficient
  • Calculated from the diffusion theory
    approximation to the Boltzmann transport
    equation
  • F(r) 8 1/r e-r µeff
  • where F(r) is the distribution of energy
    fluence in J/cm2, around an interstitially placed
    optical fibre r is the distance from the source
    to the delivery fibre in millimetres and µeff is
    the effective attenuation coefficient.

105
Optical measurements
Needle positions taken from CT scans
106
Validation of method
  • Intralipid phantom with green ink
  • ?s 1, ? a 0.01 ? ?eff 0.17 mm-1

107
Variation in penetration depth
108
Intensities along a line between two rows of
cylindrically diffusing fibres.
109
Future work
  • 6-8 further patients in part A
  • 20 patients in part B effect of multiple fibres
  • Phase 3 study
  • Biopsy verification
  • Focal therapy study
  • Selectivity study

110
Future work
  • 6-8 further patients in part A
  • 20 patients in part B effect of multiple fibres
  • Phase 3 study
  • Biopsy verification
  • Focal therapy study
  • Selectivity study

111
Transperineal, template-guided biopsies

Anterior
1
4
2
3
10
7
6
Mid
5
8
9
11
12
13
14
15
Posterior
a apex b base
112
Transperineal, template-guided biopsies Sagital
view - apex / base nomenclature
17mm core
Position 8a
Position 8b
17mm core
113
Future work
  • 6-8 further patients in part A
  • 20 patients in part B effect of multiple fibres
  • Phase 3 study
  • Biopsy verification
  • Focal therapy study
  • Selectivity study

114
Comparison of Dextran-FITC leakage from tumor
vessels induced by WST09 assisted by FIVVM
0
5
10
Before Illumination
After 10min
Light intensity 150mW/cm2 WST09, 10mg/kg
0
Neumark, Madar, Slava
Mouse ear model. MADB106 (Rat Mammary Carcinoma
Xenographt)
115
Conclusion
  • In evaluation phase
  • Has been useful in other disease areas - head and
    neck
  • Complexity may be an attribute
  • Photosensitisers will improve
  • Delivery systems will improve

116
Tissue ablation technologies
  • Cryotherapy
  • HIFU
  • Photo-dynamic therapy
  • Radio frequency tumour ablation
  • Interstitial self-regulating rods

Gillett et al. Mayo Clin Proc. 2004 Dec 79 (12)
1547-1555
117
Radio frequency Interstitial Tumour Ablation
(RITA)
  • Radio-frequency to generate heat energy
  • Rods are cooled
  • Most work done in liver, lung, kidney
  • Small body of literature
  • Problems have included
  • Tissue dessication
  • Lack of real time imaging
  • Controlling the size of lesion

118
Radio frequency Interstitial Tumour Ablation
(RITA)
  • Phase I / II trial
  • 11 patients, 8/11 radiation failures
  • T2 or less, N0 M0
  • Performed in office setting
  • Focal treatment
  • 20 month follow-up

Shariat et al. Prostate 2005 65(3) 260-267
119
Radio frequency Interstitial Tumour Ablation
(RITA)
  • gt50 PSA reduction 9/11 men
  • At 12 month review 50 NED
  • Mean PSA DT increased from
  • 14 /- 13 months to 37 /- 22 months
  • Toxicities
  • Haematuria 20
  • Bladder spasms 9
  • Dysuria 9

Shariat et al. Prostate 2005 65(3) 260-267
120
Radio frequency Interstitial Tumour Ablation
(RITA) - Conclusions
  • Relatively invasive
  • Too early to have an opinion
  • Controlling the lesion may be the key problem
  • Familiar energy source
  • Ultrasound signal processing will help in
    treatment planning

121
Tissue ablation technologies
  • Cryotherapy
  • HIFU
  • Photo-dynamic therapy
  • Radio frequency tumour ablation
  • Interstitial self-regulating rods

Gillett et al. Mayo Clin Proc. 2004 Dec 79 (12)
1547-1555
122
Interstitial self-regulating rods
  • Palladium / Cobalt alloy
  • Heat up when place in an alternating magnetic
    field
  • Multiple treatments at predetermined temperature
  • Adjunct to EBRT
  • Primary therapy

Tucker et al. J Endourol 2003 17(8) 601-7
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Interstitial self-regulating rods
  • 4 patients
  • ltT2 N0 M0, Gleason score 7 or less
  • 70 C rods
  • Ultrasound control
  • Flouroscopy
  • Confluent thermal destruction
  • End to end , 1 cm apart
  • 40 watts per minute per gm of tissue
  • 3/4 NED

Tucker et al. J Endourol 2002 60(1) 166-9
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Summary
  • A number of technologies
  • All in rapid evolution
  • Current data poor and historical
  • HIFU at present looks the most promising for
    primary therapy
  • Salvage treatments likely to increase
  • Diffusion of therapy likely to precede evidence
    base
  • May be the future

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126
Supplementary Slides
127
Salvage radiation following radical prostatectomy
  • Analysis of 501 men
  • Pooled analysis
  • 45 month median follow up
  • Failure defined by
  • PSA rise 0.1 ug/L above nadir
  • Use of androgen suppression

Carroll et al. Urol Oncol 2004 22 (6)498-9
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Salvage radiation following radical prostatectomy
  • Results
  • 50 experienced disease progression
  • 10 developed metastases
  • 4 died of cancer
  • 4 died of other causes
  • 4 year Progression Free Probability (PFP)
  • 45 (40 to 50)

Carroll et al. Urol Oncol 2004 22 (6)498-9
129
Salvage radiation following radical prostatectomy
Men with no adverse features had 4 year PFP of
77 (64 to 91)
Carroll et al. Urol Oncol 2004 22 (6)498-9
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Salvage radiation following radical prostatectomy
  • Men with Gleason 8-10 ve margins PSA lt 2ug/L
  • PSADT gt 10m PFP 81 (57 to 100)
  • PSADT lt/ 10m PFP 37 (16 to 58)
  • Men with PSA lt 2 ug/L Gleason 4-7 PSADTlt10m
  • ve margin PFP 64 (51 to 76)
  • - ve margin PFP 22 (22 to 38)

Carroll et al. Urol Oncol 2004 22 (6)498-9
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Salvage radiation following radical prostatectomy
  • Patients free of recurrence at 4 years
  • Gleason 8-10 15
  • PSADT lt / 10 months 38
  • Disease free interval lt 12m 70

Carroll et al. Urol Oncol 2004 22 (6)498-9
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