Title: Minimally invasive ablation therapies for localised prostate cancer is this the way forward
1Minimally invasive ablation therapies for
localised prostate cancer -is this the way
forward?
- Mark Emberton
- Institute of Urology University College
LondonLondon
2Harms 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
3Estimate 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.
4Estimate 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
55 year urinary and sexual outcomes after radical
prostatectomy
N1288
Penson et al. J Urol 2005 173 (4) suppl 451
6The 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
7Editorial 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
8Tissue ablation technologies
- Use thermal energy to create tissue destruction
- Numerous technologies
- Different states of
- Evaluation
- Diffusion
- Degrees of invasiveness
- Very poor evidence base
9Tissue 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
10Tissue ablation technology - desirable attributes
Gillett et al. Mayo Clin Proc. 2004 Dec 79 (12)
1547-1555
11Tissue 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
12Current 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
13Technological 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
14Cryoablation 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
15Combined 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
16Combined 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.
17Combined Cryo Series Biochemical Outcomes by
Risk Groups
18Combined Cryo Series Complications
19Cryotherapy - 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
20Cryotherapy - 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
21Cryotherapy as a salvage intervention
22The 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
23Salvage therapy key questions
- Is the disease
- Localised ?
- Disseminated ?
- Both ?
- What are the objectives of salvage therapy?
24Salvage options
Androgen suppression can be applied throughout
25Salvage 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-
26Diagnosis of local recurrence following radiation
failure
- Predictors of recurrence following radiation
therapy
27SALVAGE 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
28Modern Cryobiology
1st Generation 2nd Generation 3rd Generation
- More even temperature distribution
29Salvage 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
30Salvage 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
31Salvage 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
32Salvage 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
33Salvage 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
34Focal 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
35Focal 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
36Conclusions (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
37Tissue 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
38Principles of High Intensity Focused Ultrasound
39Principles 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
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50Case 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
51HIFU 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
52HIFU 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
53Japanese 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
54Japanese experience with Sonablate 500
- Cancer control
- 97 Freedom from biochemical progression
- Negative Biopsy 100
Uchida T et al. Jap. J. Endourol. 2004
16108-114
55Japanese 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
56Five year outcome comparisons
- Biochemical Disease Free Survival
BDFS definitions do vary but are comparable
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58(No Transcript)
59Where 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
60Where 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
61Multi-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)
62Where 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
63Salvage 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.
64Salvage 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.
65Salvage 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.
66Can 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.
67Rationale
- Salvage therapies following brachytherapy are
limited - Brachytherapy failures are usually excluded from
salvage trials - Seeds may impact HIFU energy delivery.
68Seed Implantation under Ultrasound Guidance
Brachytherapy Seeds
Prostate
Rectal Cavity
Base
Apex
Sonablate500 Ultrasound Sector (Transverse)
Image Plane
69Prostate X-Ray Images
70Sonablate500 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
71Treatment Plan
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75HIFU 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.
76Prostate X-Ray Images
Apex
7
6
5
4
3
2
1
7 Sections, 5 mm spacing
Base
77Prostate Histology
Prostate Section X-Ray Image
Paraffin Block Fix
HE Stained Slide
78Prostate Histology
Rectal Lining
Approximate Seed Location
79Conclusions
- 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
80Summary Salvage Therapies
- No evidence of disease (NED) rates and negative
biopsy status
Heterogeneity in disease severity, comorbidity
and definition of failure
81Where 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
82Where 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
83Where 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
84Conclusions
- Minimally invasive
- Reliable technology
- A surgical intervention
- Technology in evolution
- European initiative
- Varied indications
- Outcomes lack precision, but are likely to
improve
85Tissue 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
86Photodynamic
therapy
accumulation
application
therapy
laser
12
9
3
6
photosensitiser
87PHOTODYNAMIC THERAPY (PDT)
88(No Transcript)
89Aim 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
90Methodology
- 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
91Trial 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) -
92Trial 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.)
-
93Study Visits
94Needles in the prostate prior to light delivery
95Transrectal ultrasound during PDT
96Theatre staff, fibre placement and monitoring
equipment
97Treatment 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
98Treatment plan - Sagital section
Diffuser fibre (D)
Monitor fibre (M)
2- 4 cm fibre
Catheter plus Monitor fibre
Stabiliser needle
L2
L1
Sphincter active area
99Patients 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)
100Patient 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
101A
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
103Side 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
104Calculation 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.
105Optical measurements
Needle positions taken from CT scans
106Validation of method
- Intralipid phantom with green ink
- ?s 1, ? a 0.01 ? ?eff 0.17 mm-1
107Variation in penetration depth
108Intensities along a line between two rows of
cylindrically diffusing fibres.
109Future 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
110Future 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
111Transperineal, 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
112Transperineal, template-guided biopsies Sagital
view - apex / base nomenclature
17mm core
Position 8a
Position 8b
17mm core
113Future 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
114Comparison 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)
115Conclusion
- 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
116Tissue 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
117Radio 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
118Radio 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
119Radio 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
120Radio 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
121Tissue 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
122Interstitial 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
123Interstitial 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
124Summary
- 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
125(No Transcript)
126Supplementary Slides
127Salvage 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
128Salvage 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
129Salvage 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
130Salvage 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
131Salvage 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