Improving the Diagnosis and Treatment of Localised Prostate Cancer

Lead Research Organisation: University College London
Department Name: Surgery

Abstract

The way we diagnose prostate cancer at the moment is flawed. At present, a blood test called the prostate specific antigen, or PSA, is used to decide who gets a prostate biopsy. Prostate biopsy is painful, causes bleeding and sometimes serious infections. It often detects harmless cancers that need no treatment and misses important cancers that do. This is because prostate biopsies are random - we cannot see the cancer so needles are fired into the prostate in the hope that we will hit the cancer.

Once diagnosed, the way we treat early prostate cancer can cause a lot of harm. Current treatments for early prostate cancer target the whole prostate, causing damage to surrounding structures. This can lead to urine leak, poor erections and back passage problems.

The research

I will test the ability of several markers in blood and urine as well as imaging to accurately predict the presence or absence of important prostate cancer.

I will also test whether treating the cancer only, in order to avoid damaging surrounding structures, is effective in cancer control and whether the harms of whole-gland treatments can be reduced.

The possible benefits

Reduce the number of men who undergo unnecessary prostate biopsy
Reduce the risk of being diagnosed with a harmless prostate cancer
Improve the diagnosis of prostate cancer that is important
Reduce the harms of treatment

Technical Summary

To improve the diagnosis and treatment pathways in prostate cancer so that fewer and better biopsies are taken with fewer and better treatments conducted.

Objectives

A. To evaluate the ability of novel tissue and imaging biomarkers to detect and rule-out clinically significant prostate cancer (fewer and better biopsies, fewer treatments)
B. To evaluate the genito-urinary, bowel, quality of life and cancer control outcomes after a issue-preserving strategy that targets only the area of prostate cancer (better treatments)

Design and Methodology

The two objectives will be evaluated in the following way:

A. Fewer and better biopsies, fewer treatments

1. Collect and store tissue samples and imaging data-files from men prior to biopsy
2. Validate known diagnostic tests in detecting and ruling-out clinically significant prostate cancer,
a) tissue biomarkers: urinary MSMB, serum kallikreins and PTEN-associated glycoproteins
b) imaging datafiles: diffusion-weighted and dynamic contrast enhanced MRI quantitative parameters and ultrasound tissue characterisation algorithms
3. Conduct a discrete choice experiment to evaluate men‘s preferences for, and trade-offs between, the attributes of different diagnostic strategies and tests

B. Better treatment

1. Conduct a phase II multicentre trial to evaluate the,
a) precision and reproducibility of genitourinary, rectal and health-related quality of life outcomes
b) medium-term histological outcomes of treated and untreated prostate tissue
c) clinical validity of tissue and imaging biomarkers in detection of local failure after focal therapy
2. Develop a predictive model, using tissue and imaging biomarkers to predict outcomes after focal therapy
3. Conduct a formal consensus panel meeting of international experts to discuss and develop a pragmatic randomised controlled trial protocol comparing focal therapy to standard of care

Scientific and Medical Opportunities

A. Fewer and better bisies, fewer treatments

1. A risk calculator that may identify men who require a biopsy so that detection of clinically significant disease is improved and men with insignificant disease can avoid an unnecessary biopsy and treatment
2. A unique collection of blood and urine samples and imaging datafiles, linked to template mapping biopsy findings, that can be used to test future promising biomarkers of prostate cancer

Better treatment

1. The development of a pragmatic phase III randomised controlled trial protocol to evaluate the long term outcomes of focal therapy compared to standard of care
2. A unique collection of pre- and post-treatment pathological samples from men in whom the dominant or index lesion has been ablated and all other cancer foci remain in-situ.

Publications

10 25 50
 
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 £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 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 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 £1,100,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 09/2013 
End 08/2016
 
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 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