Prostate Brachytherapy for intermediate risk patients

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Prostate Brachytherapy for intermediate risk
patients

• David Bottomley
• Cookridge Hospital
• Leeds

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Intermediate risk patients

• Gleason gt 6 (exclude Gleason 9, 10)
• PSA gt 10 lt 20
• gtT2
• 1 risk factor allowed, otherwise high risk

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PARTIN TABLESLOW RISK

• T1-T2, Gleason lt 6, PSA lt 10
• CP 9 - 44
• SV 0 - 5
• LN 0 - 4

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DFS POST SURGERY WITH ECE ANDNEGATIVE MARGINS
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EXTRAPROSTATIC EXTENSION
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RADIAL EXTENT OF EXTRAPROSTATIC DISEASE (EPD)
c T1-T2/ Gl lt 6/ PSA lt 10

• DAVIS 107 SPEC.
• 10 demonstrated EPD
• Mean extension 0.03 mm
• Max. extension 0.6 mm

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PARTIN TABLESINTERMEDIATE RISK

• T1-T2, Gleason gt6, PSA lt 10
• T1-T2, Gleason lt 7, PSA 10-20
• CP 30 - 57
• SV 4 - 24
• LN 1 - 16

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MAGNITUDE OF ECE VS PSA/GLEASON
Soyhada
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POST-IMPLANT CT DOSIMETRY SEATTLE IMPLANTS
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MONOTHERAPY TREATMENT MARGINS(26 Patients,
13,104 Data Points)
Merrick, Wallner
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PURPOSE OF ADDING EXTERNAL BEAM

• Addresses disease potentially beyond implant
  range
• Capsule penetration
• S.V. Invasion
• Indicated if any one factor present
• gt T2 / Gl gt6 / PSA gt10
• Spackle effect

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SPACKLE EFFECT OF EBRT
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THERAPEUTIC MARGIN HOW MUCH DOES 45 GY EBRT ADD?

• AMOUNT OF ADDITIONAL EXTRAPROSTATIC TISSUE
  COVERED BY THE ADDITION OF 45 GY
• ASSUMPTIONS
• Minimum cancericidal isodose line with EBRT is at
  the 50 brachy isodose
• Therapeutic margin therefore increased by 4 mm

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25mm
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THERAPEUTIC MARGINS
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MAGNITUDE OF ECE VS PSA/GLEASON
Soyhada
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bNED iPSA 10-20MONOTHERAPY VS COMBINED
Mono. Blasko Zelefsky Combined
Dattoli Critz
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I125/ Pd103 IMPLANT EBRT PSA PFS
Intermediate Risk, n 200
EBRT Implant - 84
Implant Alone - 74
Cumulative Probability
p0.16
Low T1-T2b / GSlt7 / iPSAlt10 Intermediate T2c /
GSgt6 / iPSAgt10 (1 Factor) High T2c / GSgt6 /
iPSAgt10 (2 Factors)
0.0
0
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Time post-implant (months)
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DISADVANTAGES OF ADDING EBRT

• Increased morbidity
• Decreased patient convenience
• Increased cost

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Hormones and Seed Implants

• Commonly used to downsize large prostates prior
  to seed implant
• Lee et al (IJROBP 200252(2) 444-52
• 201 Patients of intermediate high risk (Glgt6,
  PSAgt10, stagegtT2a). Follow-up 42 months
• BDFS 79 with hormones
• BDFS 54 without hormones

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Implant quality and outcome

• Stock et al 1998
• 134 patients (T1/2, Gleason lt7)
• D90 calculated
• 4 year FFBF 68 for D90lt 140 Gy
• 92 for D90gt 140 Gy
• 81 for D90100-140 Gy
• Difference greater when presenting PSAgt10

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Leeds results 3/95 12/01seeds alone 145Gy

• Patients 667
• Mean age 63 (range 42-77)
• Hormones 346 (51.9)
• PSAlt10 421 (63.1)
• Gleasonlt7 462 (69.2)
• T1-T2a 519 (77.7)

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Number of patients of each risk group and PSA
relapse-free survival rate
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I125/Pd103 IMPLANT EBRT BRFS BY RISK GROUP,
n 634
Low Risk
Intermediate Risk
High Risk
Cumulative Probability
Low T1-T2 / GSlt7 / iPSAlt10 Intermediate T3 /
GSgt6 / iPSAgt10 (1 Factor) High T3 / GSgt6 /
iPSAgt10 (2 Factors)
Patients at Risk
612 555 461 361 263 193 129 78 33
16 9 1
0.0
0
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Time post-implant (months)
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Actuarial PSA-RFS according to ESTRO risk groups
based on initial PSA and Gleason score prior to
treatment.84.3 Solid line, Low risk 73.9
dashed Intermediate risk and 52.6 dotted High
risk
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Hormones v no hormones in intermediate risk group
Ns
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Multivariate analysis to predict PSA relapse free
survival
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Influence of Gleason grade on outcome after
brachytherapy

• 1029 consecutive patients at MSK 1993-99
• All T1/T2. All had central pathology review
• 614 grade 33
• 208 grade 34
• 150 grade 43
• 57 grade 44
• Potters et al IJROBP 2003, 56(3)749-754

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Stratification of treatment
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Kaplan-Meier biochemical freedom from recurrence
(median follow-up 46m)
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Multivariate analysis of factors predicting for
BFR
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Comparison of Two I125 Monotherapy Cohorts
Biochemical Relapse Free
Low Risk Intermed. Risk
Grimm et al IJROBP 2001
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BFR
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Conclusion

• Results in medical literature conflicting for
  intermediate risk patients
• Inconclusive evidence of benefit of additional
  EBRT or NAAD
• Further studies required