Title: BeSpoke: Building and Evaluating a risk Stratified PrOstate pathway for cancer screening, detection, treatment and surveillancE
Funder: Department of Health and Social Care

Abstract: Research questionCan a bespoke approach allow us to reduce the harms and maximise the benefits of prostate cancer screening, diagnosis, monitoring and treatment? BackgroundProstate cancer screening, diagnosis, surveillance and treatment cause significant harm, missing some cancers at a curable stage, 'overdiagnosing' men with indolent disease, using invasive tests to monitor stable cancers, and asking men to choose between treatments with life-changing effects on urinary, sexual and mental health without providing them with adequately personalised information and support. Aims and objectives Design community testing to detect men at highest risk of aggressive cancer Offer good quality MRI across the UK so that cancers are not missed Develop a personalised monitoring schedule to reduce unnecessary invasive procedures and improve mental health Develop a personalised web-based tool to support men choosing between monitoring and treatments with different side effect profilesMethodsThrough a combination of leveraging existing funded work, and new studies, I will: Evaluate the response to screening across different ethnic and socio-economic groups and assess how a modified approach could include those at highest risk of prostate cancer (Re-Imagine Screening, LiMiT) Compare standard multi-parametric MRI with bi-parametric MRI and Luminal Water Fraction (LWF) to establish the most efficient approach to allow all hospitals to offer high quality MRI for prostate cancer diagnosis (PiQUAL, PRIME, Climate) Assess the impact of an MRI-led, personalised surveillance strategy (PRECISE, REASSURE), and model this in different international cohorts (PRIAS, Europe; National Institute for Health, USA) to determine a dynamic model which allows detection of cancer progression whilst allowing men with stable cancer to avoid invasive biopsies during surveillance Ascertain the relationship between MRI features, urinary and sexual health recovery and hospital episode statistics data (HES) in men after localised prostate cancer treatment (TrueNTH Post Surgery, TrueNorth Global, BeSpoke Recovery) Develop a personalised decision support tool, based on urinary and sexual health at baseline, along with MRI phenotype of the cancer and surrounding structures, to help men identify the likelihood of cancer control and sexual and urinary health after different treatments for localised prostate cancerTimelines for deliveryFrom analysis of Re-Imagine Prostate Cancer Screening I will deliver a framework for an improved community screening approach in year 1, and will assess this in LimiT in years 2 and 3. By the end of year two I will have assessed the relationship between MRI phenotype and recovery of urinary and sexual function after prostate cancer surgery. In year 3 I will develop a model for a personalised recovery prediction based on baseline questionnaire and MRI data, and this will be tested in year 4. In year 5 I will make the web-based personalised recovery prediction and active surveillance tools available for use by men and clinicians. Anticipated impact and disseminationA bespoke prostate cancer approach would see community screening to detect men at highest risk of prostate cancer, ensure all men get the right prostate MRI scan first time, see less unnecessary invasive testing, and more support for men to make a personalised treatment choice.

Lay abstract: BackgroundThe prostate cancer pathway includes screening, diagnosis, treatment and monitoring. Previous screening studies using traditional biopsy showed that prostate cancer deaths can be reduced, but at a cost of diagnosing harmless cancers whose treatment can cause life changing side effects. The UK does not have a formal screening programme, and over 16% of UK men are diagnosed when the cancer has spread outside of the prostate, and can't be cured. Hospital based diagnostic tests for prostate cancer include an MRI scan, but some hospitals are offering poor quality scans that can miss some cancers. Men with localised prostate cancer are asked to choose between different treatments and monitoring. Monitoring (active surveillance) involves hospital visits for tests, including invasive biopsies, which can cause bleeding, infections and anxiety. Nearly 40% of men being monitored show signs of poor mental health. A study of 3 000 men after prostate cancer treatment found that 1 in 3 men wear pads for urine leakage and 7 in 10 men had sexual function problems. One man described being asked to choose between treatment and monitoring as 'like going to a restaurant where you haven't heard of any of the dishes, can't see what others are having, and are asked to make a life changing decision quickly'. Current information, including the NHS Predict Prostate Cancer tool, incorporates cancer details, but not individual likelihood of life changing side effects, based on pre-treatment health.A personalised or bespoke pathway would offer screening and treatment to reduce prostate cancer death, but minimise the harms to urinary, sexual and mental health by avoiding unnecessary tests and treatment. Aims Offer community testing to men at highest risk of aggressive cancer Offer high quality MRI across the UK so that cancers are not missed Develop a personalised monitoring schedule to reduce unnecessary procedures and improve mental health Develop a personalised web-based tool to support men choosing between different treatments and monitoringDesign and methods Screening I will analyse data from an MRI based screening study, to see whether men at highest prostate cancer risk say yes to a screening invitation. We will use interviews, and community meetings to explore ways to make screening acceptable to men at highest risk. We will use this to design a new screening study. Hospital based diagnosis I will compare data from two different studies to determine the best way to get a good quality scan for all men referred for assessment. This would reduce the number of missed cancers, and allow men to get treatment for aggressive cancers more quickly. Active surveillance Most monitoring programmes ask men to have regular invasive tests, which can be uncomfortable, and cause bleeding and infections. I have developed an MRI monitoring programme led approach, where men with a stable cancer can avoid invasive tests. This professorship would allow us to see the differences between regular testing and MRI-led testing, in our group of 600 men, and a European group of 8 000 men. We can then design a tool to help reduce unnecessary tests for stable cancers. Helping men choose the right treatment for them We know that urinary and sexual health before treatment, and factors such as the length of the muscle that prevents urine leakage can help predict recovery after prostate cancer treatment. Using recovery data and MRI measurements from men, I will build a web based decision support tool, to predict the effect that different treatments would have on an individual man. Patient and public involvement Men with lived experience of prostate cancer have helped develop this proposal and will be key members of the oversight committee.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS