Introduction to Prostate
Brachytherapy
Wayne Butler, PhD
Schiffler Cancer Center
Wheeling Hospital
Prostate Cancer Death Rate
(American Cancer Society 2005)
D e a th R a te p e r 1 0 0 ,0 0 0 M e n
45
40
35
30
25
20
15
10
5
0
1930
1940
1950
1960
1970
Year
1980
1990
2000
Why the decline in incidence and mortality
over the last 10 years?
„
Improved treatment isn’t the only explanation.
„
PSA screening allows diagnosis at earlier stages
„
„
„
Earlier stage disease is more curable regardless of
improvements in technique or technology
Each year screening becomes more prevalent and each
year the average patient presents with lower risk
Survival comparisons from one time interval to another
are not valid because patient characteristics are
substantively different.
Prostate cancer clinical staging by the 2002
American Joint Committee on Cancer
Stage
Description
Substage
Description
cT1
Microscopic disease
neither palpable nor visible
on TRUS
cT1a
cT1b
cT1c
Incidental finding in ≤ 5% of tissue sample
Incidental finding in > 5% of tissue sample
Found on needle biopsy due to ↑ PSA
cT2
Palpable tumor apparently
confined within the
prostate
cT2a
cT2b
cT2c
Involves ≤ half of one lobe of the prostate
Involves > half of one lobe of the prostate
Involves both lobes of the prostate
cT3
Tumor protrudes through
the prostate capsule
cT3a
cT3b
Extracapsular extension of one or both lobes
Seminal vesicle invasion
cT4
Tumor is fixed or invades
beyond SV
cT4
Invades bladder neck, muscle, pelvic wall or
other
PSA test became widely available in 1988 to
measure at ng/mL level
„
Demolished false perceptions of treatment efficacy
„
„
“Is cure possible in those for whom it is necessary — and is
cure necessary in those for whom it is possible.”
Willet Whitmore, 1990
Test has only modest sensitivity and specificity
„
Age specific thresholds: 4.0 ng/mL for age 65 – 70
„
PSA velocity in ng/mL/yr
„
PSA density in ng/mL/cm³ of prostate
„
Measure PSA isoforms and precursor molecules
Gleason score is pathological measure of
tumor aggressiveness
„
Based on glandular architecture of stained tissue
viewed at medium microscope power
„
Well to poorly differentiated patterns are scored
from 1 to 5
„
„
Two most prevalent patterns are added to create a
composite score: e.g. grade 3 + grade 4 = GS 7
Distribution of scores by national experts:
GS ≤ 4 is rare, less than 1%
GS 5 should be about 15% of patients
GS 6 – 7 should be about 65%
GS 8 – 10 should be about 19%
Gleason grades
Assign a number corresponding
to the most predominant
glandular differentiation pattern.
Assign a number to secondary foci
of disease.
The sum of the patterns is the
Gleason score. If there is no
secondary pattern, double the
primary number.
A commonly used risk group stratification
scheme
Risk Group
Clinical
Stage
Gleason
Score
PSA
Low (0)
≤ T2b
and
≤ 10
and
≤6
Intermediate (1)
> T2b
or
> 10
or
>6
High (≥ 2)
> T2b
and /or
> 10
and /or
>6
The purpose of risk group stratification
„
Indicates likelihood of organ confined disease
„
Low risk: > 2/3
„
Intermediate: 1/3 to 2/3
„
High risk: < 1/3
„
„
Use Partin tables for accurate values of organ
confinement, extracapsular extension, seminal vesicle
and lymph node involvement
Selects patients for the most appropriate
therapy
Other selection criteria
„
Quality of life factors scored by questionnaires
„
Urinary function: IPSS
„
Erectile function: IIEF
„
Rectal function: RFAS
„
Age — older men are at higher risk of failure
„
Co-morbidities — patients should have > 5 years life
expectancy
„
Anatomy — prostates > 100 cm³ are difficult and
expensive to implant
How to compare survival across
modalities?
„
There are no randomized trials comparing surgery,
brachytherapy, and external beam
„
„
SPIRIT closed for lack of accrual despite a $5,000 per patient
institutional incentive
Single institution, multi-modality studies
„
Uniform definition of biochemical survival
„
Uniform risk group classification
• Other factors such as age differ significantly
„
No report has documented that each therapy modality was
delivered to meet a standard of quality
Intermediate risk comparison by treatment
modality — Cleveland Clinic
(Ciezki et al. IJROBP 60:1347, 2004)
Biochemical Survival (%)
100
Brachytherapy 85%
80
EBRT 78%
60
Prostatectomy 57%
40
20
p = 0.092
0
0
12
24
36
48
Months
60
72
84
Single institution comparison by treatment
modality
(Sharkey et al. Brachytherapy 4:34-44, 2005)
1
Bx Interm 89%
Bx High
Progression Free
0.8
87%
0.6
RP Interm 57%
0.4
RP High
0.2
0
0
2
4
6
Years
8
10
37%
Inter-institution and inter-modality
comparisons
„
Averaging data across published reports is subject to
selection bias
„
Search for the best reported results that have been
replicated elsewhere
„
Indicates what is achievable or possible
„
Patients stratified by standard risk groups
„
Treated in the same era
„
At least 100 patients per subgroup analyzed
„
Minimum 8 years of follow-up
„
ASTRO and nadir definitions of survival become similar at
long follow-up
Low risk, monotherapy survival comparison
by treatment modality
1
Brachytherapy 95%
RP 88%
0.8
Progression Free
3DCRT 80%
0.6
0.4
Seattle (Blasko)
MSKCC
Fox Chase
Low Risk,
Monotherapy
0.2
0
0
2
4
6
Years
8
10
Low risk, LDR and HDR brachytherapy
survival comparison with XRT boost
1
Brachytherapy 93%
HDR 92%
Progression Free
0.8
0.6
0.4
Low Risk,
Combined Modality
Atlanta (Critz)
Wm Beaumont
0.2
0
0
2
4
6
Years
8
10
Intermediate risk, monotherapy survival
comparison by treatment modality
1
Progression Free Survival
Brachy 96%
0.8
RP 78%
0.6
3DCRT 62%
0.4
Intermediate Risk,
Monotherapy
Wheeling
MSKCC
MD Anderson
0.2
0
0
2
4
6
Years
8
10
Intermediate risk, LDR and HDR survival
comparison combined with XRT boost
1
Progression Free Survival
HDR 83%
0.8
Brachy 80%
0.6
0.4
Intermediate Risk,
Combined modality
Wm Beaumont
Atlanta (Critz)
0.2
0
0
2
4
6
Years
8
10
High risk, monotherapy survival comparison
by treatment modality
1
Progression Free Survival
Brachy 89%
0.8
RP 59%
0.6
3DCRT 42%
0.4
High Risk,
Monotherapy
0.2
Mt Sinai (NY)
MSKCC
Fox Chase
0
0
2
4
6
Years
8
10
High risk, LDR and HDR survival comparison
combined with XRT boost
1
Progression Free Survival
Brachy 88%
0.8
HDR 70%
0.6
Wheeling
Oakland
High Risk,
Combined modality
0.4
0.2
0
0
2
4
6
Years
8
10
Treatment related morbidity
„
Every therapy that cures cancer has morbidity
„
„
A therapy that claims otherwise has not been
sufficiently studied, or the proponents are misinformed
or quacks
Morbidity profiles of brachytherapy, surgery, and
3DCRT differ in frequency and intensity for each
effect
„
Comparisons between modalities is beyond the scope of
this survey
Urinary, rectal and sexual effects
„
These side effects appear to follow a critical
structure threshold dose response.
„
„
Below the threshold, the effect is negligible or nonexistent
Structures at risk
„
Prostatic and bulbomembranous urethra
„
Rectal wall
„
Penile bulb
Sagittal schematic of the prostate and
nearby structures
Bladder
Corpora
cavernosum
Prostate
Penile
bulb
Seminal vesicle
Urethra
Corpora
spongiosum
Distribution of postimplant day of urinary
catheter removal
day 0: 92.6%
day 1:
day 2:
day 3:
day 4:
> day 4:
3.1%
1.6%
0.6%
0.2%
1.9%
Mean IPSS difference from preimplant baseline
(n = 976)
Mean IPSS Difference
4
2
0
-2
-4
0
12
24
36
48
M o n th s s in c e Im p la n t
60
72
Kaplan-Meier rate of return to preimplant IPSS
baseline (n = 976)
% Not Returned to Baseline
100
80
60
40
20
0
0
12
24
36
M o n th s sin ce Im p lan t
48
60
Rectal function assessment score over time
(RFAS scale 0 – 36, preimplant mean = 2.6)
1999 survey
18
2002 survey
Total RFA score
15
12
9
6
3
0
-3
12
24
36
48
60
72
Months since Implant
84
96
Perceived change in bowel function relative
to preimplant status
100
1999 survey
80
% of patients
69%
73%
2002 survey
60
40
20
12%
19%
15%
12%
0
Better
Same
Worse
Perceived change in bowel function
Sexual symptoms reported after
brachytherapy (Merrick et al. IJROBP 96:313-319, 2001)
40
% Reporting
30
Diminished orgasmic intensity
20
Orgasmalgia
10
Hematospermia
0
0
2
4
6
8
10
Months since Implant
12
14
16
Potency preservation as a function of
preimplant IIEF score (Merrick et al.)
100
Still Potent (%)
80
60
IIEF 24 – 30
57.6%
40
48.0%
IIEF 18 – 23
20
IIEF 13 – 17
22.1%
0
0
12
24
Months since Implant
36
48
Potency preservation as a function of age at
implant (Merrick et al.)
100
Still Potent (%)
80
Age < 60
60.8%
60
40
48.6%
Age 60 – 69
20
32.0%
Age ≥ 70
0
0
12
24
Months since Implant
36
48
Potency preservation stratified by penile
bulb D50 dose of 30% of prescribed dose
Potency Preservation (%)
100
D50 ≤ 30% Rx
76%
80
60
D50 > 30% Rx
32%
40
p < 0.001
20
0
0
12
24
M onths since Implant
36
48