PROSTATE BRACHYTHERAPY:
Bradley Prestidge, MD, MS, FABS
Bon Secours Cancer Institute
Norfolk, Virginia
LDR HDR
or
Audience Response Question: 1
Do you perform prostate brachytherapy?
1. No
2. LDR
3. HDR
4. Both LDR and HDR
Audience Response Question: 2
Do you use or recommend the PCTRF.org or ProstateCancerFree.org website with your prostate cancer patients?
1. Always
2. Often
3. Never
4. What the heck is that?
PCRSG: PCTRF.orgProstateCancerFree.org
6
40
50
60
70
80
90
100
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Brachy
Surgery
EBRT
CRYO
HIFU
29
22
21
5
% P
SA
Pro
gre
ssio
n F
ree
18
12
28
317
10
9
8 2
1
13
Protons
HDR
Years from Treatment →
15
436
37
38
+
Seeds Alone
Seeds + ADT40
Robot RP
41
42
44
43
45
46
Intermediate Risk Results
7
11
14
20
35
34
39
2324
16
6
26
Non-Brachy
Any Brachy
EBRT & Seeds
Hypo EBRT
EBRT, Seeds + ADT
3027
47
48
49
150
151
31
152
152
153
154
155
155
156
157
158
159
19
25
32
32 160
160
33
161156
6
7
8
9
Bradley R Prestidge, MD 1, Kathryn A Winter, MS 2, Martin G Sanda, MD 3, Mahul B Amin, MD 4, William S Bice,
PhD 5, Jeff M Michalski, MD 6, Geoffrey S Ibbott, PhD 7, Juanita Crook, MD 8, Charles N Catton, MD 9, Hiram A
Gay, MD 6, Viroon Donavanik MD 10, David C Beyer, MD 11, Steven J Frank, MD 7, Michael A Papagikos, MD 12,
Seth A Rosenthal, MD 13, H Joseph Barthold, MD 14, Mack Roach III, MD 15, Howard M Sandler, MD 4
A Phase III Study Comparing Combined External Beam
Radiation and Transperineal Interstitial Permanent
Brachytherapy with Brachytherapy Alone for Selected Patients
with Intermediate Risk Prostatic Carcinoma
ASTRO PLENARY SESSION
1 DePaul Medical Center, Bon Secours Cancer Institute , 2 NRG Oncology Statistics and Data Management Center , 3 Emory University ,4 Cedars-
Sinai Medical Center , 5 John Muir Medical Center , 6 Washington University School of Medicine , 7 UT MD Anderson Cancer Center, 8 University of
British Columbia , 9 Princess Margaret Hospital , 10 Christiana Care Health Services, Inc. CCOP , 11 Cancer Centers of Northern Arizona, 12 Coastal
Carolina Radiation Oncology, 13 Sutter Medical Group, 14 South Suburban Oncology Center , 15 UCSF Medical Center
RTOG 0232: Study Schema
S
T
R
A
T
I
F
Y
Stage
T1cT2a – T2b
Gleason Score
≤ 67
PSA
0 - < 1010 - 20
NeoadjuvantHormonalTherapy
NoYes
R
E
C
O
R
D
Isotope
I-125
Pd-103
R
A
N
D
O
M
I
Z
E
Arm 1: 45 Gy EBRT
Partial pelvis (1.8
Gy/fraction M-F for five
weeks) followed 2-4
weeks later by Pd-103
(100 Gy) or I-125 (110 Gy)
OR
Arm 2: Pd-103 (125 Gy) or I-125 (145 Gy)
Overall Survival
p = 0.41
Biochemical Failure
ASTRO Definition Phoenix Definition
p = 0.18 p = 0.74
RTOG 0232: Summary of Worst Late Radiation Toxicity
GradeEBRT + Brachy(n=284)
%BrachyOnly
(n=290)%
1 74 26.1 84 29.0
2 102 35.9 74 25.5
3 26 9.2 16 5.5
4 1 0.4 1 0.3
5 0 0 0 0
ASCENDE-RT
NCCN IR and HR risk group
Randomized
DE-EBRT arm12m ADT, 8m neo-adjuvant46 Gy whole pelvis EBRT78 Gy 3-DCRT boost
LDR-PB arm12m ADT, 8m neo-adjuvant46 Gy whole pelvis EBRTLDR 115 Gy I125 boost
FU:Clinical visits: q6 mo – to 5 y and annually afterwardsPSA and Testosterone - q6mo
Morris, et al. IJROBP 2016
Results: Biochemical PFSIntent-to-treat analysis of the primary endpoint
121086420
time since first LHRH injection (yrs)
1.0
0.8
0.6
0.4
0.2
0.0
prop
ortio
n fr
ee o
f rec
urre
nce
LDR-PB ARM
DE-EBRT ARM
Kaplan-Meier
(95% CI)
Randomization(N=398)
DE-EBRT
(N=200)
LDR-PB
(N=198)
PFS
5 yr83.8
(±5.6)
88.7
(±4.8)
7 yr75.0
(±7.2)
86.2
(±5.4)
9 yr62.4
(±9.8)
83.3
(±6.6)
Absolute difference 5y – 4.9%7y – 11.2%9y – 20.95%
Morris, et al. IJROBP 2016
121086420
time since first LHRH injection (years)
1.0
0.8
0.6
0.4
0.2
0.0
prop
ortio
n fre
e of
recu
rren
ce
LDR-PB ARM
DE-EBRT ARM
Log rank P < 0.0001Absolute difference
5y – 38.9%
7y – 42.9%
9y – 47.8%
Results: Biochemical PFS<0.2 PSA threshold
Morris, et al. IJROBP 2016
5y Cumulative Incidence of Late G3+ Toxicity
Toxicity LDR-PB DE-EBRT P-Value
GU Grade 3
Grade 4
19%
1%
5%
1%
<0.001
0.547
GI Grade 3
Grade 4
9%
1%
4%
0%
0.120
NA
GU gr3 - 50% urethral strictures
Morris, et al. IJROBP 2016
*
*
From: Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy
Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer
JAMA. 2018;319(9):896-905. doi:10.1001/jama.2018.0587
Fig. 1
Brachytherapy 2019 18, 186-191DOI: (10.1016/j.brachy.2018.12.007)
National Cancer Database. King, et al. Brachytherapy 2019
Fig. 2
Brachytherapy 2019 18, 186-191DOI: (10.1016/j.brachy.2018.12.007)
National Cancer Database. King, et al. Brachytherapy 2019
PROSTATE BRACHYTHERAPY:
LDR HDR
or
PROSTATE BRACHYTHERAPY:
?
LDR HDR
or
HIGH DOSE RATE PROSTATE BRACHYTHERAPY
Audience Response Question: 3
For those that do not perform prostate HDR brachytherapy, what is the primary reason?
1. Takes too much time
2. Lack of training
3. Lack of shielded room to do US based
4. Lack of physics support
5. Combination of above
6. Prefer other modalities (IMRT, SBRT, LDR)
NEEDLE PLACEMENT WITH REAL TIME US BASED DOSIMETRY
DOSE OPTIMIZATION
TREATMENT DELIVERY: 1-20 CHANNELS
Well Controlled Dose Distribution
31
HDR Brachytherapy
• Temporary dose
• Single source driven from an afterloader
• No patient radiation precautions
• Radiation delivery takes minutes
• Must be delivered in a shielded room CT,
MRI, or US based
General Observations (vs seeds)
• No radiation precautions
• Procedure may take longer in OR
• More compacted work – physics intensive
• Easier to do well - shorter learning curve
• Attention to detail important
• Better tolerated
• Less uropathy
Indications for Prostate HDR
• Locally Advanced Disease: Boost - ECE, SVI
• Large Prostate (>60 cc) - unable to get needles to periphery
• High IPSS - better tolerated than seeds
• Patient preference
Types of Prostate Brachytherapy
35
Low Dose Rate (LDR) High Dose Rate (HDR)Seed implant “Smart” brachytherapyPermanent TemporaryMultiple sources Single sourceVarious isotopes: I, Pd, Cs Single isotope Ir-192Single procedure Single to multiple procedures/fractionsRequires ordered sources/case Reusable, single sourceUS directed CT or US directedNo additional expensive equipment Requires HDR afterloaderGland size limits No gland size restrictionUropathy- common, moderate/severe Uropathy- less common, minimal/modOften given alone No radiation post-precautions
Types of Prostate Brachytherapy
36
Low Dose Rate (LDR) High Dose Rate (HDR)Seed implant “Smart” brachytherapyPermanent TemporaryMultiple sources Single sourceVarious isotopes: I, Pd, Cs Single isotope Ir-192Single procedure Single to multiple procedures/fractionsRequires ordered sources/case Reusable, single sourceUS directed CT or US directedNo additional expensive equipment Requires HDR afterloaderGland size limits No gland size restrictionUropathy- common, moderate/severe Uropathy- less common, minimal/modOften given alone No radiation post-precautions
3D Radiation Dose Distributions
37
LDR
HDR
Brachytherapy vs. EBRT
PATIENT ADVANTAGES
1. Less time
2. More dose
3. Less cost
4. More effective
Brachytherapy vs. EBRT
ONCOLOGIC ADVANTAGES
1. Greater RBE
2. Similar toxicity to IMRT alone
3. Improved cancer control rates
RADIOBIOLOGICAL EFFECTIVENESS
Audience Response Question: 4
Do you consider RBE in your treatment decisions for prostate cancer?
1. Somewhat (i.e. for EBRT fractionation- Hypo, SBRT)
2.Yes (i.e. comparing EBRT with brachytherapy, or boost)
3.I’d like to, but not sure about how to implement it
4.No - it’s a lot of smoke and mirrors
Stock, et al. IJROBP 64:527; 2006
FFBF BASED ON BED
Stock, et al. IJROBP 64:527; 2006
POST-TREATMENT PROSTATE BIOPSY RESULTS BASED ON PSA
BED groups Number of patients Percent positive
≤100 33 24%
>100–120 20 15%
>120–140 33 6%
>140–160 52 6%
>160–180 82 7%
>180–200 72 1%
>200 131 3% p < 0.0001
Stock, et al. IJROBP 64:527; 2006
BED EXAMPLES
ISOTOPE D90 (Gy) BEDEBRT 45 86
Pd-103 125 140
EBRT 78 143
I-125 145 153
Cs-131 115 192
EBRT/Pd-103 45/100 198
HDR 13.5 x 2 209
EBRT/HDR 45/15 x 1 211
EBRT/Cs-131 45/85 213
BED EXAMPLES
ISOTOPE D90 (Gy) BEDEBRT 45 86
Pd-103 125 140
EBRT 78 143
I-125 145 153
Cs-131 115 192
EBRT/Pd-103 45/100 198
HDR 13.5 x 2 209
EBRT/HDR 45/15 x 1 211
EBRT/Cs-131 45/85 213
Salvage Case Presentation
Healthy 72 yo AAM
Favorable IR disease – two cores GS 3+4, 1 cores 3+3, PSA 5.6
Treatment: Proton therapy, October 2016. PSA nadir 1.2
FU: PSA increase. Oct 2018 – 3.6, Jan 2019 – 5.4
Bone scan- neg. CT A/P – neg. Axumin- + midline prostate
MRI- ROI Rt mid-gland. No ECE or SVI. Otherwise negative
Biopsy – 16 cores in prostate/SV: all negative. ROI – GS 3+4 Ca
Salvage Case Presentation
65 yo WM, retired fighter pilot
Favorable IR disease – single core GS 3+4, 2 cores 3+3
Treatment: Cs-131 in Aug 2013. PSA nadir < 0.1 Aug 2015
FU: PSA increase. Aug 2018 – 0.1, Feb 2014 – 0.5, Aug 2014 – 1.8, Nov 2019 – 2.8
Bone scan- neg. CT A/P – neg. Axumin- + only in mid-right SV
MRI- no ROI. Fullness in Rt SV only. Otherwise negative
Biopsy – 12 cores in prostate: all negative. 2 cores in rt SV +