prostate brachytherapy: ldr hdr or · ldr 115 gy i125 boost fu: clinical visits: q6 mo –to 5 y...

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 +