An Evaluation of Focal Therapy in the Treatment of Localized Prostate Cancer An Evaluation of Focal Therapy in th

Lead Research Organisation: University College London
Department Name: Surgery

Abstract

The choice for men who have prostate cancer that has not spread outside the gland is between active surveillance and treating the whole gland with surgery or radiotherapy. Active surveillance involves monitoring the disease using blood tests and repeated biopsies every 2-3 years. Treatment is given only if the cancer shows signs of progressing. The benefit of whole-gland treatment in reducing the risk of dying from cancer is 5% or less within 10 years. However, treatment carries risk of incontinence, impotence and rectal problems. These occur because treating the whole gland leads to damage to structures immediately surrounding the prostate

This programme of research will see if prostate cancer management can be developed in a similar way to how breast cancer treatment changed two decades ago. Women usually had to undergo an operation to remove the whole breast whereas currently, most women undergo a lumpectomy of only the cancer. This proposal will evaluate a similar principal in prostate cancer. In other words, in men with prostate cancer can we destroy only the areas of cancer and achieve lower side-effects. At the same time, can we maintain good cancer control.

Technical Summary

Background
The choice for men who have localised prostate cancer (PCa) is between active surveillance and treating the whole gland with surgery or radiotherapy. Active surveillance involves monitoring the disease 3-monthly with biopsies and blood tests. Radical therapy is instituted if the cancer progresses. The absolute risk reduction in mortality, as demonstrated in a randomised controlled trial, from radical surgery is 5% within 10 years. This difference is probably smaller in the PSA-screened population. However, radical treatment carries risk of incontinence, impotence and rectal problems. These occur because treating the whole gland causes damage to structures surrounding the prostate.

Focal Therapy Hypothesis
Fewer side-effects and effective early cancer control can be achieved by targeting areas of prostate cancer.

Aims
1. Evaluate whether localised PCa is suitable for focal therapy
2. Evaluate localisation of PCa using magnetic resonance imaging
3. Evaluate the patient acceptability of focal therapy

Objectives
1. Determine the proportion of men that may be suitable for focal therapy in the UK on histological specimens.
2. Determine the side-effects and early cancer control of focal therapy in a trial setting.
3. Investigate the role of different MRI modalities in localising PCa against prostate mapping biopsies.
4. Investigate the attributes of focal therapy that will make it acceptable for men with PCa using discrete choice analysis

Design and Methods
1. Review of histological whole-mount specimens and prostate template mapping biopsies
2. Conduct of 2 phase II trials in which malignant areas will be identified using prostate mapping biopsies and ablated using high-intensity focused ultrasound (HIFU). HIFU causes coagulative necrosis using a rectal probe to transmit sound-waves that heat up discrete areas to 80-90°C. One trial will evaluate hemiablation for unilateral PCa and the other will evaluate focal-ablation of low-volume cncer areas on both sides.
3. MRI localisation accuracy of PCa will be analysed using prostate mapping biopsies as a reference standard. Qualitative analysis and quantitative visual analysis will be used to assess accuracy of dynamic contrast enhanced and diffusion weighted MRI.
4. Discrete choice experimentation, an accepted approach for elicitation of preferences of one treatment over another, will assess the key attributes of focal therapy from a patient perspective.

Research Training
This programme will equip the applicant for an academic career in Clinical Epidemiology involving practice-oriented translational and health services research such as clinical trial methodology and health technology evaluation (therapeutic and diagnostic test evaluation) (all are MRC priority capacity development areas and priority areas in the Walport report). The MSc in Clinical Trials and attendance at discrete choice analysis workshops and UCL Skills development programme will be a formal part of this training. In addition, specific training in medical image analysis/processing and histopathological evaluation will form important basic research skill elements. Clinical training in core urology as well as sub-specialist training in ablative techniques (HIFU, cryosurgery, photodynamic therapy, radio-frequency ablation) will equip the applicant for practice as a Consultant Urologist. These elements will form a strong basis for independent post-doctoral research.

Publications

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publication icon
Afaq A (2018) Impact of Ga-Prostate-Specific Membrane Antigen PET/CT on Prostate Cancer Management. in Journal of nuclear medicine : official publication, Society of Nuclear Medicine

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Ahmed HU (2013) Editorial comment. in The Journal of urology

 
Guideline Title GUIDELINE ON PROSTATE CANCER 2012
Description Citation within the EAU prostate cancer guidelines
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact The EAU guidelines are followed around Europe and internationally in the USA, Japan, Australia/NZ so have major impact. They cite focal therapy and my work and as a result numerous centres have started focal therapy programmes allowing greater access to the treatment.
 
Description Focal therapy in prostate cancer
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Multiple international centres have started focal therapy in prostate cancer clinical programmes as a result of our trial results published and covered in international publicity in April 2012
 
Description MRI prior to prostate biopsy
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Multiple sites around the world have sarted MRI programmes to diagnose prostate cancer as a result of this work which was widely publicised and published/presented at international conferences.
 
Guideline Title Focal therapy using high-intensity focused ultrasound (HIFU) for localised prostate cancer (IPG424)
Description NICE Focal HIFU guidelines
Geographic Reach National 
Policy Influence Type Citation in clinical guidelines
Impact The NICE guidance allows physicians to use Focal HIFU within a registry or trials. As a result, about 10-15 surgeons in the UK have started focal therapy programmes in the UK
 
Description Challenge Award
Amount $1,000,000 (USD)
Organisation Prostate Cancer Foundation 
Sector Charity/Non Profit
Country Global
Start 10/2012 
End 09/2015
 
Description Electroporation for Focal Therapy of Prostate Cancer
Amount £34,000 (GBP)
Funding ID G2011/53 
Organisation Prostate Cancer UK 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2012 
End 02/2014
 
Description HTA Diagnostic Call
Amount £2,300,000 (GBP)
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start 10/2011 
End 10/2015
 
Description Image Registration for Prostate Cancer TRUS biopsy
Amount £74,000 (GBP)
Organisation Prostate Cancer UK 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2012 
End 06/2014
 
Description Imaging in Prosate Cancer
Amount £48,000 (GBP)
Organisation Prostate Cancer UK 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2010 
End 06/2011
 
Description MRC Clinician Scientist
Amount £1,200,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2011 
End 10/2016
 
Description Multi-parametric ultrasound in the detection of clinically significant prostate cancer
Amount £180,000 (GBP)
Funding ID PG13-025 
Organisation Prostate Cancer UK 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2014 
End 11/2016
 
Description PROMIS-T Biobank
Amount £195,000 (GBP)
Organisation Prostate Cancer UK 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2011 
End 10/2014
 
Description PRX302 in the focal treatment of prostate cancer
Amount £750,000 (GBP)
Organisation Sophiris Bio 
Sector Private
Country United States
Start 11/2014 
End 10/2016
 
Description Project Grant
Amount £12,000 (GBP)
Organisation Pelican Cancer Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2013 
End 11/2014
 
Description Prostate Cancer Research Foundation
Amount £40,000 (GBP)
Organisation Prostate Cancer UK 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2009 
End 09/2011
 
Description Prostate Cancer UK Project grant
Amount £285,845 (GBP)
Funding ID PG13-026 
Organisation Prostate Cancer UK 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2014 
End 02/2016
 
Description Prostate UK
Amount £25,000 (GBP)
Organisation Prostate Cancer UK 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2009 
End 05/2010
 
Description Radiofrequency ablation for treatment of prostate cancer
Amount £320,000 (GBP)
Organisation Trod Medical 
Sector Private
Country Belgium
Start 10/2014 
End 09/2016
 
Description Smart Surgery
Amount £2,200,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2012 
End 09/2015
 
Description St Peters Trust
Amount £20,000 (GBP)
Organisation St Peter's Trust for Kidney, Bladder and Prostate Research 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2010 
End 05/2011
 
Description St Peters Trust
Amount £50,000 (GBP)
Organisation St Peter's Trust for Kidney, Bladder and Prostate Research 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2009 
End 02/2012
 
Description Tissue Type Imaging for Prostate Cancer
Amount £250,000 (GBP)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 12/2011 
End 03/2014
 
Description UCH/UCL NIHR CBRC
Amount £191,000 (GBP)
Organisation National Institute for Health Research 
Department UCLH/UCL Biomedical Research Centre
Sector Public
Country United Kingdom
Start 07/2008 
End 07/2010
 
Description Wellcome Trust Senior Clinical Fellowship
Amount £2,038,776 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Senior Research Fellowship
Sector Private
Country United Kingdom
Start 09/2017 
End 08/2022
 
Description i4i
Amount £100,000 (GBP)
Organisation National Institute for Health Research 
Department NIHR i4i Invention for Innovation (i4i) Programme
Sector Public
Country United Kingdom
Start 11/2010 
End 09/2011
 
Description i4i
Amount £1,100,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 09/2013 
End 08/2016
 
Description FP7 Erasmus Medical Centre 
Organisation Advanced Medical Diagnostics
Country United States 
Sector Private 
PI Contribution EU FP7 Application for Euro 6Million consortium shortlisted. Ahmed and Emberton at UCL are coordinators (Focal therapy in Prostate Cancer project). Decision due March 2010
Collaborator Contribution EU FP7 Application for Euro 6Million consortium shortlisted. Ahmed and Emberton at UCL are coordinators (Focal therapy in Prostate Cancer project). Decision due March 2010EU FP7 Partner (shortlisted)EU FP7 Consortium partnerEU FP7 Consortium industrial partnerEU FP7 Industrial partner
Impact Consortium involving Lille Universty Hospital, INSERM-Lille (France), Uppsala (Sweden), and Erasmus University Medical Centre.
Start Year 2009
 
Description FP7 Erasmus Medical Centre 
Organisation EDAP TMS
Country France 
Sector Private 
PI Contribution EU FP7 Application for Euro 6Million consortium shortlisted. Ahmed and Emberton at UCL are coordinators (Focal therapy in Prostate Cancer project). Decision due March 2010
Collaborator Contribution EU FP7 Application for Euro 6Million consortium shortlisted. Ahmed and Emberton at UCL are coordinators (Focal therapy in Prostate Cancer project). Decision due March 2010EU FP7 Partner (shortlisted)EU FP7 Consortium partnerEU FP7 Consortium industrial partnerEU FP7 Industrial partner
Impact Consortium involving Lille Universty Hospital, INSERM-Lille (France), Uppsala (Sweden), and Erasmus University Medical Centre.
Start Year 2009
 
Description FP7 Erasmus Medical Centre 
Organisation Erasmus University Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution EU FP7 Application for Euro 6Million consortium shortlisted. Ahmed and Emberton at UCL are coordinators (Focal therapy in Prostate Cancer project). Decision due March 2010
Collaborator Contribution EU FP7 Application for Euro 6Million consortium shortlisted. Ahmed and Emberton at UCL are coordinators (Focal therapy in Prostate Cancer project). Decision due March 2010EU FP7 Partner (shortlisted)EU FP7 Consortium partnerEU FP7 Consortium industrial partnerEU FP7 Industrial partner
Impact Consortium involving Lille Universty Hospital, INSERM-Lille (France), Uppsala (Sweden), and Erasmus University Medical Centre.
Start Year 2009
 
Description FP7 Erasmus Medical Centre 
Organisation National Institute of Health and Medical Research (INSERM)
Department Lille (INSERM)
Country France 
Sector Public 
PI Contribution EU FP7 Application for Euro 6Million consortium shortlisted. Ahmed and Emberton at UCL are coordinators (Focal therapy in Prostate Cancer project). Decision due March 2010
Collaborator Contribution EU FP7 Application for Euro 6Million consortium shortlisted. Ahmed and Emberton at UCL are coordinators (Focal therapy in Prostate Cancer project). Decision due March 2010EU FP7 Partner (shortlisted)EU FP7 Consortium partnerEU FP7 Consortium industrial partnerEU FP7 Industrial partner
Impact Consortium involving Lille Universty Hospital, INSERM-Lille (France), Uppsala (Sweden), and Erasmus University Medical Centre.
Start Year 2009
 
Description FP7 Erasmus Medical Centre 
Organisation Uppsala University
Country Sweden 
Sector Academic/University 
PI Contribution EU FP7 Application for Euro 6Million consortium shortlisted. Ahmed and Emberton at UCL are coordinators (Focal therapy in Prostate Cancer project). Decision due March 2010
Collaborator Contribution EU FP7 Application for Euro 6Million consortium shortlisted. Ahmed and Emberton at UCL are coordinators (Focal therapy in Prostate Cancer project). Decision due March 2010EU FP7 Partner (shortlisted)EU FP7 Consortium partnerEU FP7 Consortium industrial partnerEU FP7 Industrial partner
Impact Consortium involving Lille Universty Hospital, INSERM-Lille (France), Uppsala (Sweden), and Erasmus University Medical Centre.
Start Year 2009
 
Description Focal Salvage Trial (NCRN FORECAST Trial) 
Organisation University College London
Department Centre for Medical Image Computing
Country United Kingdom 
Sector Academic/University 
PI Contribution I am lead PI on the FORECAST trial. I have written the protocol and will be guarantor on its conduct and reporting.
Collaborator Contribution The CMIC group are conducting image registration and image analysis of the imaging data collected
Impact Collaboration with imaging scientists, radiologists and pathologists for each aspect of the trial.
Start Year 2013
 
Description Image registration 
Organisation University College London
Department Centre for Medical Image Computing
Country United Kingdom 
Sector Academic/University 
PI Contribution Clinical data and image data for registration modelling
Collaborator Contribution Data collection of MRI scans and ultrasound 3D data for registration and fusion. EU FP7 application for Focal Therapy mutlicentre European trial (shortlisted) HTA MRI Prostate Study (successful) (£2M)
Impact Successful HTA NIHR project (£2M) (Ahmed is coordinator and co-PI) Shortlisted for MRC DPFS (Ahmed is co-applicant) (£0.5M) Shortlisted for EU FP7 Health programme (Ahmed is coapplicant and coordinator) NIHR Comprehensive Biomedical Research centre grant (£100,000) (Co-applicant)
Start Year 2007
 
Description Intratumour heterogeneity in prostate cancer 
Organisation Cancer Research UK
Department Cancer Research UK London Research Institute (LRI)
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Co-applicant on grant from Prostate Cancer Foundation
Collaborator Contribution Clinical Lead applicant for project
Impact US PCF grant
Start Year 2012
 
Description Intratumour heterogeneity in prostate cancer 
Organisation Institute of Cancer Research UK
Country United Kingdom 
Sector Academic/University 
PI Contribution Co-applicant on grant from Prostate Cancer Foundation
Collaborator Contribution Clinical Lead applicant for project
Impact US PCF grant
Start Year 2012
 
Description Intratumour heterogeneity in prostate cancer 
Organisation University College London
Department UCL Cancer Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Co-applicant on grant from Prostate Cancer Foundation
Collaborator Contribution Clinical Lead applicant for project
Impact US PCF grant
Start Year 2012
 
Description Magnetic nanoparticle therapy for prostate cancer 
Organisation The Royal Institution of Great Britain
Country United Kingdom 
Sector Academic/University 
PI Contribution Lead applicant
Collaborator Contribution NIHR i4i grant success in developing new therapy
Impact Grant success
Start Year 2012
 
Description Prostate MR Imaging Study 
Organisation Institute of Cancer Research UK
Country United Kingdom 
Sector Academic/University 
PI Contribution Lead PI for collaboration
Collaborator Contribution Clinical Trial design and management of PROMISMethodological input to trial Translational elements of PROMIS
Impact NIHR HTA grant (£3.2Million) 2010-2015 Multidisciplinary between between Computer Science, Radiology, Oncology, Urology and MRC Clinical Trials Unit
Start Year 2009
 
Description Prostate MR Imaging Study 
Organisation Medical Research Council (MRC)
Department MRC Clinical Trials Unit
Country United Kingdom 
Sector Public 
PI Contribution Lead PI for collaboration
Collaborator Contribution Clinical Trial design and management of PROMISMethodological input to trial Translational elements of PROMIS
Impact NIHR HTA grant (£3.2Million) 2010-2015 Multidisciplinary between between Computer Science, Radiology, Oncology, Urology and MRC Clinical Trials Unit
Start Year 2009
 
Description SmartTarget 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution Co-applicant (co-Lead on clinical)
Collaborator Contribution Collaborative application to Wellcome Trust/DoH HICF SmartSurgery call
Impact Urological Surgery Clinical Trials Health Economics and Health Services Research Computer and Engineering Science
Start Year 2011
 
Description SmartTarget 
Organisation University College London
Department Centre for Medical Image Computing
Country United Kingdom 
Sector Academic/University 
PI Contribution Co-applicant (co-Lead on clinical)
Collaborator Contribution Collaborative application to Wellcome Trust/DoH HICF SmartSurgery call
Impact Urological Surgery Clinical Trials Health Economics and Health Services Research Computer and Engineering Science
Start Year 2011
 
Description SmartTarget 
Organisation University College London
Department Comprehensive Clinical Trials Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution Co-applicant (co-Lead on clinical)
Collaborator Contribution Collaborative application to Wellcome Trust/DoH HICF SmartSurgery call
Impact Urological Surgery Clinical Trials Health Economics and Health Services Research Computer and Engineering Science
Start Year 2011
 
Title Focal Therapy 
Description Phase II Fcal therapy Hemiablation HIFU NCRI Trial completed (in publication stage). 
Type Therapeutic Intervention - Radiotherapy
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2009
Development Status Under active development/distribution
Impact Shortlisted for multicente phase II EU FP7 Focal Therapy HIFU trial 
 
Title Multifunctional MRI in detection of prostate cancer 
Description Multifunctional MRI in detection of prostate cancer is used in the MRC funded trials to localise disease for focal therapy. This phase II data has shown good accuracy for localisation of disease and has now been progressed to a large scae study as a result. 
Type Diagnostic Tool - Imaging
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2009
Development Status Under active development/distribution
Impact NIHR HTA Trial (Ahmed and Emberton lead PIs) awarded (£2M) to validate multifunctional MRI 
 
Company Name Nuada Medical 
Description As a result of this work they now offer private MRIs and mapping biopsies pioneered in this work prior to prostate biopsy and have set up a dedicated MRI scanner on Harley Street. This type of practice is now being duplicated across a number of other private hospitals 
Year Established 2012 
Impact Change in private practice referral patterns around Harley Street
Website http://www.nuadamedical.co.uk/nm-about.html
 
Description 'My Man' campaign (Prostate Cancer Research Centre charity). 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Radio Interviews: 'My Man' campaign (Prostate Cancer Research Centre charity). 13 local radio stations including 10 independent and 3 BBC.

Increased awareness and recrutment to trials.
Year(s) Of Engagement Activity 2009
 
Description Annual National Meeting of the Prostate Support Group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Lecture on 'The role of focal therapy in prostate cancer.'

Increased awareness and recruitment to trials
Year(s) Of Engagement Activity 2007
 
Description Focal Therapy trial results 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact All terristorial news channels (BBC, Channel 4, ITN, Channel 5), multiple international news channels, multiple radio (national and International), 4 national UK newspapers and one front page (Telegraph) covered this story in April 2012. Press release via MRC Press Office

International recognition of MRC funded trial in novel focal therapy of prostate cancer
Year(s) Of Engagement Activity 2012
 
Description Foreign Press Association 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Prsentation on focal theapy in prostate to Foreign Press rganisation of 15 journalists from around the world

Newspaper publicity on research
Year(s) Of Engagement Activity 2009
 
Description Newspaper interviews 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Newspaper interviews in relation to article: HIFU in the management of prostate cancer - the first UK results. Daily Telegraph, Daily Mail, The Times, Daily Express, BBC Website.

Increased recruitment to trials
Year(s) Of Engagement Activity 2008,2009
 
Description Norfolk and Norwich Prostate Support Group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Lecture on 'Prostate cancer management: minimally invasive treatments.'

Increased recruitment to trials run under MRC funding
Year(s) Of Engagement Activity 2007
 
Description UCL Tour d'Europe 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact 200 oncologists and urologists from Europe attended this event

None
Year(s) Of Engagement Activity 2013