1. Manit Arya Consultant Urological Surgeon UCLH and PAH Transforming the Pathway in Prostate Cancer

2. Prostate Cancer 40, 975 new cases/yr 10,793 deaths/yr Lifetime risk of 18% (doubled in PSA era) Lifetime risk of death PCa 3.4% Commonest cancer and 2 nd leading cause of death in men Post mortem data: ~30% in 40s, 60% in 60s, 80% in 80-- ‐ 90s

3. Diagnosis

5. TRUS biopsy complications: False negative rate Haematospermia - 37.4% Haematuria > 1 day 14.5% Rectal bleeding < 2 days 2.2% Prostatitis 1.0% Fever > 38.5°C (101.3°F) 1 – 6% Epididymitis 0.7% Rectal bleeding > 2 days ± requiring surgical intervention 0.7% Urinary retention 0.2% (up to 4.6%) Other complications requiring hospitalisation 0.3% Quote own department figures TRUS Biopsy

6. Clinically indolent cancers are identified by chance Important cancers are incorrectly classified as unimportant Clinically significant lesions are missed The errors that result from the current pathway... Men undergo whole-gland treatment which carries harm

7. Template Transperineal Biopsies

8. Excellent diagnostic accuracy. Detects > 95% of clinically significant prostate cancer and of those testing negative, at least 95% really are free of clinically significant cancer. Can sample every 5mm of the prostate if necessary – usually 20 or 12 zones Performed under general anaesthetic Template Transperineal Biopsies

9. Template transperineal prostate biopsies – 20 zone Barzell protocol

10. BUT New kid on the block as a diagnostic test

11. Multi-parametric MRI

12. Evidence suggests MP-MRI detects 70-90% of those who do and 70-90% of those that do not have clinically significant prostate cancer (in our hands 95% sensitivity and specificity in detecting significant prostate cancer) Images of entire prostate  T2W (low signal in presence of cancer),  Diffusion (higher ratio of membrane to water in cancer)  Dynamic contrast enhancement (higher, faster rate of contrast in tumours due to blood supply) Non-invasive, takes ~ 1 hour Pre-biopsy MP-MRI using T2, diffusion weighted images and dynamic contrast enhanced images becoming established as standard practice as a triage test to identify those who need biopsies Role of multi-parametric MRI

13. MP-MRI Targetted Transperineal Biopsies Reduces number of biopsies Reduces detection of insignificant cancer Transperineal targeted biopsies under local anaesthetic are feasible, tolerable and accurate

14. Elevated PSA TRUS biopsy Positive ±MRI 6/52 Treatment Active Surveillanc e Negative Current Diagnostic Pathway

15. Elevated PSA MP-MRI Positive Targetted transperineal biopsies LA / sedation Treatment Active Surveillance Negative New Diagnostic Pathway

16. Treatment

17. So, …we have a target… … can we treat just that target… … as opposed to the whole prostate i.e. radical prostatectomy or radiotherapy?

18. The question is not new in the cancer field Breast cancerLumpectomy Thyroid cancerHemithyroidectomy KidneyPartial nephrectomy LiverPartial resection In fact, almost all other non-haemaotological cancers

19. We can accurately localise prostate cancers

20. We now have the tools to treat just the tumour and not the whole prostate…

21. Difficult to surgically remove only part of the prostate Need energy source that will result in cancer cell death and that can be accurately targetted/ focused to affected areas - HIFU / cryotherapy

22. Cryotherapy High Intensity Focused Ultrasound Brachytherapy Interstitial Photothermal Laser Irreversible Electroporation Photodynamic Therapy Radiofrequency Ablation

23. Focal Therapy

24. HIFU with the Sonablate ® System The Sonablate ® 500 is a medical device that uses HIFU to thermally ablate the prostate.

25. Rectal Probe/ Transducer

26. FOCAL HIFU

27. Focal HIFU Therapy

30. Cryotherapy Tissue ablation through localised delivery of extreme cold AND subsequent thawing Delivery of freezing and thawing gases is via hollow probes Argon (-187.7 0 C) gas used to freeze - Joule Thompson (J-T) effect Helium gas used to thaw

31. Focal Cryotherapy

32. Example from the Cohort Mr GM, 64 years, Gl 3+3 on AS since 2008, PSA 8

33. Example from the Cohort

36. Mr Markham

37. Post-operative MP-MRI

38. Focal Therapy: Decreases Morbidity of Whole Gland Therapy Incontinence Impotency Rectal injury Recuperation

39. Radical prostatectomy Radical radiotherapyFocal Therapy Rectal injury1-2% (fistula)3% long term severe proctitis <1% Impotence40-60%25-60% (occurs over several years) 5% Incontinence50% early (10% long-term) 1% (severe long-term)1% Complications

40. Focal Therapy Advantages Day surgery procedure Bloodless Low morbidity Quick recovery Radiation free Can be repeated Can be used in radiotherapy failures Disadvantages No long term (10-20 years) outcome data Probably not suitable for high risk prostate cancer Need for comparative trials against current ‘standard’ therapies? Will we be able to recruit?

41. Prediction Four Prostate cancer is the last cancer in which we insist upon treating the whole organ harbouring the cancer… …Tissue preservation, both active surveillance and focal therapy, will reduce the over-treatment burden of localised disease

42. Elevated PSA MP-MRI Targetted transperineal biopsies Localised cancer Decision- making Active surveillance SurgeryRadiotherapy Failure Watchful waiting +/- hormones No cancer Focal HIFU/Cryotherapy Recurrence The new pathway…? MRI ‘negative’