Focal Therapy for Localised Prostate Cancer SOGUG 2012 Miss Louise Dickinson NIHR Academic Clinical Fellow/ SpR in Urology Division of Surgery and Interventional Science, UCL & Department of Urology, University College Hospital London
Over-treatment
The errors that result from the current strategy... Clinically indolent cancers are identified by chance Clinically significant lesions are missed Important cancers are incorrectly classified as unimportant Men undergo whole-gland treatment which carries harm
The Potential Solution...? Not all cancer has the potential to progress to invasive and metastatic cancer Novel imaging and biopsy techniques can identify those lesions that are likely to progress Selective therapy to Clinically Significant lesions alone could be as effective as whole-gland treatment and carry less harm
Improvements in imaging and biopsy techniques are driving a change in practice
Improved detection and localisation
Increasing global interest
Focal Therapy A potential strategy for reducing treatment related morbidity whilst offering cancer control A strategy that follows the approach taken for other solid organ tumours Breast Renal Penile
Cryotherapy Hemiablation Courtesy Lambert et al, 2007
Cryotherapy Focal Therapy Series Reported Onik et al (2009) (Endocare) Ellis et al (2007) (Endocare) Lambert et al (2007) (Oncura) Bahn et al (2006) (Endocare) Crawford/ Barqawi (2009) (Endocare) COLD Registry (2009) (Endocare) No. 112 60 25 31 100 795 Therapy Hemi Hemi Hemi Hemi Focal Focal/Partial Biopsy Template TRUS TRUS TRUS +Doppler Template TRUS Mean PSA (ng/ml) 8.3 7.2 +/- 4.7 6 (range 1-13) 4.95 5.2 +/- 4.1 Gleason Score 6 </=8 </=7 </=7 </=7 </=8 Potency 85% 70.6% 70.8% 89% 83% 65% Incontinence 0% 3.6% 0% 0% - 2.8% F/U (mean, months) 43.2 15.2 28 70-12 Disease control 93% NED 76.7% (biopsy) 88% (>50% nadir reduction) 96% (biopsy) 92% (ASTRO) 97% (biopsy at 12/12) 4.5% (36/295) 25% (36/199) 83% (ASTRO) 14
High Intensity Focused Ultrasound
UCL Trials in Focal Therapy using HIFU Hemi-HIFU Trial Focal-HIFU Trial Lesion Control HIFU Trial
Prostate Mapping Biopsies Barzell and Onik, 2009
Hemi-HIFU Trial... 89% of men achieved the trifecta status of pad-free, leak-free continence, erections sufficient for intercourse and cancer control at 12 months.
Lancet Oncology, April 2012
Focal HIFU results
The INDEX Study PIs: Ahmed/Emberton Co-ordinator: Dickinson NCRN-adopted Industry supported Ahmed, Dickinson, Emberton Ogden, Parker, Thompson, Van As, Abel, Hrouda, Winkler Brewster, Leslie Hindley Persad van der Meulen Mulhall
140 men with localised PCa Focal HIFU 1-2 weeks TWOC, contrast-mri 6 weeks, 3*, 6 and 9* months: PSA, questionnaires 12 months: mp-mri, TRUS biopsy of treated side 18*, 24, 30* month follow up 36 months mp-mri, Template biopsies, 38* months Tissue Biobank Imaging Databank Histology Biobank Serum, germline Kallikreins PTEN glycoproteins Imaging Biomarkers MRI CAD USS Tissue Characterisation Histological Biomarkers discovery TMA 22
Vascular targeted photodynamic therapy European Multi-centre Phase III Randomised Controlled Trial Low risk disease Active surveillance versus Photodynamic therapy
6 month biopsy negative for cancer
Other potential focal therapies February 2012
Other potential focal therapies
The Future for Image Targeted Therapies?
Pre-operative contouring of lesion
Biomechanical model generation MR contours used to form a finite element mesh (FEM) model Gland deformation Probe- (or MR-coil-) induced prostate deformation
Intra-operative contouring
n = 17 with additional treatment margins in 10/17 Average time = 7 minutes (4 16)
Conclusions Focal therapy is demonstrating encouraging genito-urinary functional outcomes within early, small, short-term studies Medium and long-term outcomes are awaited from prospective clinical trials and prospective registries Advances in techniques for localising clinically significant disease may allow more targeted diagnostics and therapies
Minimally-Invasive Prostate Intervention (MIPI) Group Division of Surgery and Interventional Science, UCL Prof Mark Emberton (Honorary Consultant Urologist) Mr Hashim Uddin Ahmed (MRC Clinician Scientist) Mrs Caroline Moore (Clinical Lecturer) Mr Manit Arya (Senior Clinical Lecturer and Consultant) Mr Paul Cathcart (Senior Clinical Lecturer and Consultant) Mr Paras Singh (NIHR Academic Clinical Fellow) Miss Louise Dickinson (NIHR Academic Clinical Fellow) Miss Lucy Simmons (Research Fellow) Mr Massimo Valerio (EAU Research Fellow) Department of Academic Radiology, UCLH NHS Trust Dr Clare Allen (Consultant Radiologist) Dr Alex Kirkham (Consultant Radiologist Dr Shonit Punwani (Consultant Radiologist) Dr Rowland Illing (Academic Radiology Registrar) National Medical Laser Centre Professor Steve Bown Dr Sandy Mosse Department of Histopathology, UCLH NHS Trust Dr Alex Freeman (Consultant Histopathologist) Dr Charles Jameson (Consultant Histopathologist) Centre for Medical Imaging Science, UCL Professor David Hawkes Dr Dean Barratt (Royal Academy Senior Research Fellow) Mr Yipeng Hu (MSc Student) Clinical Effectiveness Unit, RCS(England) & LSHTM Professor Jan van der Meulen Dr Susan Charman (Senior Lecturer in Epidemiology) Veeru Kasivisvanathan (Academic Clinical Fellow in Urology) Eleni Anastasiadis (Academic Clinical Fellow in Urology) Academic and Charity Supporters Commercial Supporters