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Prof Stephen Langley

Focal Brachytherapy UK experience. Prof Stephen Langley. Professor of Urology St Luke’s Cancer Centre, Guildford, UK PGMS, University of Surrey. Is there a problem?. Prostate Cancer Focality. 13-38% cancer are unifocal.

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Prof Stephen Langley

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  1. Focal Brachytherapy UK experience Prof Stephen Langley Professor of Urology St Luke’s Cancer Centre, Guildford, UK PGMS, University of Surrey

  2. Is there a problem?

  3. Prostate 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

  4. Prostate 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

  5. Ideal for Focal Therapy: BXT Eggener et al, J Urol 2007, 178 2260  • 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     

  6. Terminology: 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 Focal Ultra-Focal

  7. Imaging Preferred 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:

  8. Dosimetric Effects of Focal BXT

  9. Male Urethra

  10. Urethral Planning

  11. 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

  12. IPSS change similar to whole gland toxicity • Little change in potency IIEF 19-20 throughout • No incontinence: ICS • No rectal toxicity Mean IPSS

  13. 6 patients biopsied: whole gland • N=5: no cancer • N=1: 1mm Gleason 3+3 contralateral base to that implanted. Patient on Active Surveillance Mean PSA Yrs

  14. A Prospective Stage 2S Clinical Trial Evaluating Hemi-Ablative (LDR) Brachytherapy for Localised Prostate Cancer 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.

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

  16. A Prospective Stage 2S Clinical Trial Evaluating Hemi-Ablative (LDR) Brachytherapy for Localised Prostate Cancer • Patient 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

  17. A Prospective Stage 2S Clinical Trial Evaluating Hemi-Ablative (LDR) Brachytherapy for Localised Prostate Cancer

  18. Sponsor: NHS R&D RSCH LREC: Approved Jan 2013

  19. 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.

  20. F Brachytherapy Stranded seed, 1cm spacing Loose seed, variable spacing CTV FPTV PTV FCTV

  21. A Prospective Stage 2S Clinical Trial Evaluating Hemi-Ablative (LDR) Brachytherapy for Localised Prostate Cancer Follow up • Day 0 CT • PSA, EN2, MHI: 3, 6 ,9, 12, 18, 24m • 24m mpMRI • 24m TTB of untreated side • Standard follow up

  22. To date ….

  23. Financial Disclosures

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