prof stephen langley professor of urology st luke’s cancer centre, guildford, uk pgms, university...

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



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


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

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



To date ….To date ….

Financial DisclosuresFinancial Disclosures

prof stephen langley professor of urology st luke’s cancer centre, guildford, uk pgms, university...

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