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

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

6. 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 2260 BXT

8. 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 Ultra- Focal Focal

9. Imaging Preferred Imaging modality, mpMRI T1/T2, Diff weighting, DCE For 0.5ml tumourNPV 95%, PPV 77% Sens. 90%, Spec. 88% Villers A, et al. J Urol 2006; 176:

10. Dosimetric Effects of Focal BXT

11. Male Urethra

12. Urethral Planning

13. 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

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

16. 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

17. Hemi-Ablative Prostate Brachytherapy (HAPpy) 1 o 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 Evaluating Hemi-Ablative (LDR) Brachytherapy for Localised Prostate Cancer

18. 2 o 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

19. 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

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

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

22. Brachytherapy F Brachytherapy Simple clinic U/S (H, W, L 3 ). Nomogram calculation of seed requirement. Preloaded stranded seeds implanted peripherally. Real-time planning. Loose seeds implanted centrally. 4 th D: Average 40 min per implant.

23. F Brachytherapy FCTV FPTV ParameterCriteria Prescription Dose145 Gy V 100 >95% V 150 50-60% D 90 140-160 Gy Urethra V 150 < 15% Rectum D 0.1cc < 200Gy PTV CTV Stranded seed, 1cm spacing Loose seed, variable spacing

24. 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 Evaluating Hemi-Ablative (LDR) Brachytherapy for Localised Prostate Cancer

25. To date ….

26. Financial Disclosures