Nieuwe Toepassingen van Prostaat Brachytherapie · Randomized Phase 3 Study On The Assessment Of...

Nieuwe Toepassingen van Prostaat Brachytherapie

Bradley PietersAcademisch Medisch Centrum /

Universiteit van Amsterdam

Young 1926

Retropubic Prostate Implant Technique

Perineal prostate implantation

• Perineal technique• Ultrasound guided• Ultrasound probe on

immobilizer• Template

Holm, J Urol 1983

Brachytherapy Boost

EBRT vs. Brachy

Hoskin, Radiother Oncol 2012

Late Toxicity

Hoskin, Radiother Oncol 2012

NCCN Intermediate- and High-riskPSA ≤ 40 ng/ml

< T3bProstate volume ≤ 75 cm3

R

3D-CRT46 Gy pelvis32 Gy boost

3D-CRT + Brachy46 Gy pelvis

115 Gy I-125 boost

Ascende-RT

biochemical Progression Free Survival Overall Survival

Morris et al. Int J Radiat Oncol Biol Phys. doi: 10.1016/j.ijrobp.2016.11.026.

Increased Toxicity with LDR Brachytherapy?

Rodda et al. Int J Radiat Oncol Biol Phys 2017; 98:286-295

Incidence Prevalence

GU GU

GI GI

Urethral Stricture

Less risk urethra stricture

• Periapical V150 < 0.8 ml

• Apical urethra dose < 174 Gy

• Distance 100% isodose line < 1.1 cm from apex

Earley et al, Radiother Oncol 2012

Urethral Stricture

Merrick et al, J Urol 2006

Most predictive•Bulbomembranous dose•Supplementary EBRT

PROBACH

Randomized Phase 3 Study On The Assessment Of Late Toxicity By Comparing IMRT High Dose External

Beam Radiotherapy Only With External Beam Radiotherapy Combined With HDR Or PDR

Brachytherapy In Patients With Intermediate/high Risk Prostate Cancer

Intermediate / High Risk Prostate Cancer

R

IMRT 35 x 2.2 Gy IMRT 20 x 2.2 Gy+

1 x 13 Gy HDR

Toxicity Assessment

JAMA. 2018;319(9):896-905. doi:10.1001/jama.2018.0587

1809 patients:EBRT + BT is associated with lower PCA specific Mortality

HDR Monotherapy

HDR brachytherapy monotherapy: Planning aim

34 Gy in 4 fractions36-38 Gy in 4 fractions31.5 Gy in 3 fractions26 Gy in 2 fractions

Published HDR monotherapy studies

From Zamboglu et al IJROB 2013

718 patients: 38Gy/4f/48hrs38Gy/4f/15days34.5Gy/3f/6weeks

Zamboglou et al. Int J Radiat Oncol Biol Phys 2013;85:672-678

Acute toxicity

Late toxicity

Zamboglou et al. Int J Radiat Oncol Biol Phys 2013;85:672-678

Multifractionated schedules

Biochemical control 85%-99%

GU grade 2 1.5%-25%

GU grade 3 0%-9.2%

GI grade 2 0%-13%

GI grade 3 0%-2%

Most common4-9 fractions

SBRT?

Spratt et al. Brachytherapy 2013;12:428-433

BRAG-Peak

BRACH-Peak

Single Dose HDR Brachytherapy

Toxicity Single Dose

Morton et al. Radiother Oncol 2017:122;87-92

QOL of Single Dose

Morton et al. Radiother Oncol 2017:122;87-921

QOL and Single Dose

UrinaryIncontinence

UrinaryIrritative

Bowel Sexual Hormonal

Gomez-Iturriaga et al. Radiother Oncol 2017;126:278-2822

Single Dose Equivalent to 2-3 Fractions

1 x 19-20 Gy 2 x 13 Gy 3 x 10.5 Gy

Hoskin et al. Radiother Oncol 2017:124:56-60

FFBR

T1-2 92% Gleason 6 84% PSA≤ 10 ng/ml

No grade 3-4 late toxicity

Single dose1 x 19-20 Gy

High biochemical control and low toxicityHoskin et al. Radiother Oncol 2017:124:56-60Morton et al. Radiother Oncol 2017:122;87-92Gomez-Iturriaga et al. Radiother Oncol 2017;126:278-282

Caution for biochemical failurePrada et al. Radiother Oncol 2016;119:411-416

Primary Focal Brachytherapy for Prostate Cancer

Donovan JL et al. N Engl J Med 2016;375:1425-1437.

Outcomes for Urinary Function and Effect on Quality of Life.

Outcomes for Sexual Function and Effect on Quality of Life.

Use of padsErectile firmnessSexual quality of life

Active monitoring Superior for:

PROTECT trial

Keyes et al. Brachytherapy 2015;14:334-341

Erectile Dysfunction after Brachytherapy

100% full potency 100% partial potency

Erectile Dysfunction

Author Erectile function(%)

Stone I125 61 Urology 2007;69:338-342

Bottomley I125 42 Radiother Oncol 2007;82:46-49

Cesaretti I125, Pd103 32-68 BJUI Int 2007;100:362-67

Sanchez-Ortiz I125, Pd103 49 Int J Impot Res 2000;12:S18-S24

Merrick I125, Pd103 39 Int J Radiat Oncol Biol Phys2002;52:893-902

Mabjeesh I125 80 Int J Impot Res 2005;17:96-101

Merrick I125, Pd103 59 Int J Cancer 2001;96:313-319

Taira I125, Pd103 56 Int J Radiat Oncol Biol Phys2009;75:639-648

Budäus et al. Eur Urol 2012;61:112-127

Functional Outcomes and Complications Following Radiation Therapy for Prostate Cancer: A Critical Analysis of the Literature

Focal therapy for localised unifocal and multifocal prostate cancer: a prospective development study

Ahmed et al. Lancet Oncol 2012;13:622–632

Pad-freeLeak-freeErections sufficient for penetration

Dosimetric analysis

Hemigland Target Hemigland contralateral Whole gland

D90 153.8 Gy 47.5 Gy

V100 93.1% 24.6%

D0.1cm3 NV 219.8 Gy 62.9 Gy

D30 urethra 150.4 Gy 175.6 Gy

D2cm3 rectum 75.5 Gy 94.9 Gy

Laing et al. Radiother Oncol 2016:121:310-315

Erectile Function After partial Treatment

Yap et al. Eur Urol 2016;69:844-851

IIEF development from 3 prospective studies with HIFU• Hemi trial• Focal trial• Lesion-Control trial

POWERPartial Or Whole gland for ERections

Randomized trial for the evaluation of erectile dysfunction after whole or partial gland prostate

brachytherapy

Randomization

Whole gland Hemigland

Hypothesis Primary Endpoint• 50% ED @ 5 years (Control arm)• 30% ED @ 5 years (Experimental arm)

• ∆20%, Type I error 5% (1-sided), Power 90%

• 127 patients in each arm (254 total)

• Statistics: Cox-regression analysis and Kaplan-Meier curves

Conclusions

• Brachytherapy as boost result in superior biochemical control– GU side effects can be a concern

• HDR Monotherapy results are comparable to LDR for low- and intermediate-risk PCA

• Further investigations necessary to evaluate safety of single dose HDR brachytherapy

• Partial prostate brachytherapy is investigational in studies to follow