Prof Stephen LangleyProfessor of Urology

St Luke’s Cancer Centre, Guildford, UK

PGMS, University of Surrey

Focal BrachytherapyFocal Brachytherapy

UK experienceUK experience

Is there a problem?Is there a problem?

Prostate Cancer FocalityProstate Cancer Focality• 13-38% cancer are unifocal. • Of multifocal tumours, in 97% the Gleason grade

of the index tumour was the same as the grade of the overall cancer.

• PFS relates to index tumour volume not secondary tumour Stamey, Urology 2002

• Multifocal tumours, 80% of the total volume arises from the index lesion.

• 512/1832 (28%) of RP patients ECE was evident with 92% of extensions from the index lesion.

• In low risk PAC, 28% unifocal lesions with 1% showing EPE.

Arora et al, Cancer 2004

Ohori et al, J Urol 2006

Prostate Cancer FocalityProstate Cancer Focality• Multiple studies have suggested that non-index

lesions have little if any clinical significance

Noguci et al, J Urol 2003

Karavitakis et al, Nat Rev Clin Onc 2011

Mouraviev et al, BJUInt 2011

Ideal for Focal Therapy: Ideal for Focal Therapy:

• Tumour-cidal activity throughout target zone• Real-time monitoring• Minimal-access approach to gland• Minimal collateral effects outside treatment

focus• Cost effective• Allows re-treatment or subsequent whole

gland radical treatment

Eggener et al, J Urol 2007, 178 2260BXTBXT

Terminology: Focal BXTTerminology: Focal BXT

• CTV: Whole gland plus 3mm margin• F-GTV: Gross visible/detectable tumour• F-CTV:F-GTV + clinically insignificant disease• F-PTV : F-CTV + planning margin to allow for

uncertainties in treatment delivery

Ultra-Focal

Focal

ImagingImagingPreferred Imaging modality, mpMRI

• T1/T2, Diff weighting, DCE

• For 0.5ml tumour NPV 95%, PPV 77%

Sens. 90%, Spec. 88%Villers A, et al. J Urol 2006; 176:

Dosimetric Effects of Focal Dosimetric Effects of Focal BXTBXT

Male UrethraMale Urethra

Urethral Planning

• N=21• Clinical & MRI staging T1c-

T2a• PSA<10, Vol <75cc• Unilateral Gleason ≤3+4• No core <50% cancer• <25% cores involved• >20 Biopsy cores taken

• Real-time technique, loose seeds

• Ultra-focal approach, using mpMRI & biopsy map

• Mean Vol R 34% (20-48)• Uniform seed distribution• F-PTV 145Gy, no CT• PSA FU-(Phoenix), MRI &

Biopsy 1-2yrs

0

2

4

6

8

10

12

Months

Pre fBXT

2m

6m

12m

• IPSS change similar to whole gland toxicity

• Little change in potency IIEF 19-20 throughout

• No incontinence: ICS• No rectal toxicity

Mea

n I

PS

S

0

1

2

3

4

5

6

7

8

0 0.5 1

• 6 patients biopsied: whole gland

• N=5: no cancer• N=1: 1mm Gleason 3+3

contralateral base to that implanted.

Patient on Active Surveillance

Mea

n P

SA

Yrs

Hemi-Ablative Prostate Brachytherapy (HAPpy)

1o Objectives

• To determine if focal brachytherapy shows improved rates of toxicity compared to whole-gland LDR brachytherapy.

• To determine if focal brachytherapy is associated with similar local disease control rates as whole-gland LDR brachytherapy for low and intermediate prostate cancer.

A Prospective Stage 2S Clinical Trial A Prospective Stage 2S Clinical Trial Evaluating Hemi-Ablative (LDR) Brachytherapy Evaluating Hemi-Ablative (LDR) Brachytherapy

for Localised Prostate Cancerfor Localised Prostate Cancer

A Prospective Stage 2S Clinical Trial A Prospective Stage 2S Clinical Trial Evaluating Hemi-Ablative (LDR) Brachytherapy Evaluating Hemi-Ablative (LDR) Brachytherapy

for Localised Prostate Cancerfor Localised Prostate Cancer

2o Objectives

• To histologically assess the untreated prostate at 2-years post hemi-ablative treatment.

• To determine the clinical validity of mp-MRI to predict the presence of recurrent prostate cancer on TTB biopsies.

• To assess the value of serum PSA & urinary EN2 in predicting clinical outcome

A Prospective Stage 2S Clinical Trial A Prospective Stage 2S Clinical Trial Evaluating Hemi-Ablative (LDR) Brachytherapy Evaluating Hemi-Ablative (LDR) Brachytherapy

for Localised Prostate Cancerfor Localised Prostate CancerPatient Eligibility

• TRUS Bx (if taken): unilateral disease only

• mp-MRI • Targeted template biopsy (TTB):

unilateral disease only, &Gleason < 7 (either 3+4 or

4+3)• Stage T1-T2b N0 M0 • Serum PSA < 15• Prostate volume < 50cc• Life expectancy > 10 years• No previous radiation therapy• No previous hormone treatment

A Prospective Stage 2S Clinical Trial A Prospective Stage 2S Clinical Trial Evaluating Hemi-Ablative (LDR) Brachytherapy Evaluating Hemi-Ablative (LDR) Brachytherapy

for Localised Prostate Cancerfor Localised Prostate Cancer

Sponsor: NHS R&D RSCHLREC: Approved Jan 2013

Brachytherapy Brachytherapy F Brachytherapy Brachytherapy

• Simple clinic U/S (H , W , L3).• Nomogram calculation of seed requirement.• Preloaded stranded seeds implanted peripherally.• Real-time planning.• Loose seeds implanted centrally.• 4thD: Average 40 min per implant.

F Brachytherapy Brachytherapy

FFCTVCTVFFPTVPTV

Parameter Criteria

Prescription Dose 145 Gy

V100 >95%

V150 50-60%

D90 140-160 Gy

Urethra V150 < 15%

Rectum D0.1cc < 200Gy

PTVPTVCTVCTV

Stranded seed, 1cm spacing Loose seed, variable spacing

Follow up• Day 0 CT• PSA, EN2, MHI:

3, 6 ,9, 12, 18, 24m

• 24m mpMRI• 24m TTB of untreated side• Standard follow up

A Prospective Stage 2S Clinical Trial A Prospective Stage 2S Clinical Trial Evaluating Hemi-Ablative (LDR) Brachytherapy Evaluating Hemi-Ablative (LDR) Brachytherapy

for Localised Prostate Cancerfor Localised Prostate Cancer

To date ….To date ….

Financial DisclosuresFinancial Disclosures