Trial of Randomised Approaches for National Screening FOR Men (TRANSFORM)
| ISRCTN | ISRCTN13801649 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13801649 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 343441 |
| Protocol serial number | CPMS 57097, Grant Code: MA-BD22-001 |
| Sponsor | Imperial College London |
| Funders | Prostate Cancer UK, National Institute for Health and Care Research |
- Submission date
- 24/09/2025
- Registration date
- 21/10/2025
- Last edited
- 21/10/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Each year in the UK, nearly 50,000 men will be diagnosed with prostate cancer and over 12,000 will die of the disease. Prostate cancer often doesn’t cause any symptoms until it has started to grow or has spread outside of the prostate, so early detection is critical. However, there is currently no national screening programme for prostate cancer.
A screening programme could save thousands of lives each year, but clear evidence that screening could detect life-threatening prostate cancers early whilst avoiding unnecessary harm is needed. Screening with existing tests like the PSA (Prostate-Specific Antigen) blood test has potential downsides, such as invasive biopsies for men who do not actually have cancer and overdiagnosis and overtreatment of low-risk cancers that may not require medical intervention.
There are several highly promising tests that may overcome many of the known harms of PSA-based screening. For example, short Prostagram™ MRI scans performed in the community or saliva-based genetic tests (polygenic risk scores) may detect a similar number of the most serious prostate cancers whilst leading to fewer biopsies and fewer unnecessary treatments. However, the NHS needs strong evidence to decide whether these new screening methods should be introduced and whether they are a good use of NHS resources. TRANSFORM aims to provide the definitive evidence for prostate cancer screening.
Who can participate?
TRANSFORM is an invitation-only trial, which means participants will be randomly selected from participating General Practices and invited through a letter in the post. Men who are aged 50-74 years will be invited. Black men and those with learning disabilities are known to have poorer outcomes from prostate cancer, so will be invited from the age of 45 years.
Men with prostate cancer, or who have had any prostate cancer investigations in the previous 5 years (PSA blood test, prostate MRI, prostate biomarker test, prostate biopsy), or who have had a urinary tract infection in the previous 3 months will not be invited. In addition, men with serious health conditions such as metastatic cancer or severe frailty that is likely to limit their life expectancy to below 10 years will not be invited.
What does the study involve?
The study will have two stages:
Stage 1 (pilot and feasibility) will test four different Prostate Health Checks to decide which is the optimal screening strategy to take forward to the main trial:
Prostate Health Check 1: PSA blood test. Prostagram™ MRI scan for PSA levels 3.0ng/mL or greater.
Prostate Health Check 2: PSA blood test. Prostagram™ MRI scan for PSA levels 1.0ng/mL or greater.
Prostate Health Check 3: Prostagram™ MRI scan for all.
Prostate Health Check 4: Saliva test for polygenic risk score (PRS). Prostagram™ MRI scan if PRS indicated an elevated risk of developing prostate cancer.
Additionally, Stage 1 will test two different study designs. Design 1 involves a two-stage consent process whereby participants are identified via GP practices and invited to join the TRANSFORM Research Cohort. Those that consent will then be randomised to one of the four Prostate Health Checks or to a control group. In Design 2, men will be identified via GP practice lists then randomised directly to one of the four Prostate Health Checks or to a control group. The optimal trial design will be taken forward to the main study.
Stage 1 will also include setting up Transform Discovery, a tissue repository which will collect samples from consenting participants including blood, urine, saliva, and stool to create a unique “Biodigital Twin” for each participant, allowing real-time testing of novel biomarkers to aid prostate cancer detection.
Stage 2 (main trial) will take forward the most robust design and screening test(s) based on Stage 1 data, in order to assess whether the new screening strategy is beneficial and value for money. Stage 2 will recruit up to 500,000 participants with long-term follow-up through linkage to national databases to assess whether screening men with Prostate Health Checks reduces deaths from prostate cancer without increasing the level of avoidable harms.
What are the possible benefits and risks of participating?
Most men who join the study will not test positive for prostate cancer and will therefore not directly benefit, but participating in the trial will provide vital information to researchers about the best way to screen all men for prostate cancer. Some men will benefit by testing positive for localised prostate cancer which may not have otherwise been identified until it was too late to cure. A smaller group of men will be diagnosed with prostate cancer that is too late to cure.
A small proportion of men will screen positive in the study and will be offered a prostate biopsy (which is a part of standard care for diagnosing prostate cancer). Prostate biopsy has some risks such as blood in the urine, retention of urine, and infection.
Where is the study run from?
The study is run by Imperial College London with support from several leading Universities in the UK.
When is the study starting and how long is it expected to run for?
Stage 1 will start in December 2025 and will enrol participants for around 2 years. Stage 2 will be the much larger main trial starting in 2028. Timelines for Stage 2 will be updated on ISRCTN when it starts.
Who is funding the study?
1. Prostate Cancer UK (PCUK)
2. National Institute for Health and Care Research (NIHR) (UK)
Who is the main contact?
Prof. Hashim U Ahmed, transform@imperial.ac.uk
Contact information
Scientific
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-
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United Kingdom
| n.klimowska@imperial.ac.uk |
Principal investigator
Imperial College London
B Block
Hammersmith Hospital
Du Cane Road
London
W12 0NN
United Kingdom
 ORCID ID |
0000-0003-1674-6723 |
|---|---|
| Phone | +44 (0)20 7594 1660 |
| hashim.ahmed@imperial.ac.uk |
Scientific
Imperial College London
B Block
Hammersmith Hospital
Du Cane Road
London
W12 0NN
United Kingdom
| Phone | +44 (0)20 7594 1660 |
|---|---|
| f.rawlins@imperial.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomized controlled study |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Trial of Randomised Approaches for National Screening FOR Men (TRANSFORM) |
| Study acronym | TRANSFORM |
| Study objectives | Stage 1: pilot and feasibility Trial design optimisation: 1. Assess feasibility of pre- and post-randomisation consent designs in terms of screening uptake (overall and in specific sub-groups) and rates of contamination in the control groups. 2. Investigate which recruitment approaches are most effective in terms of rate of recruitment, number of men recruited in specific sub-groups and uptake of screening. 3. Investigate barriers and facilitators to participation in, and compliance to, screening interventions at each screening round within different socio-economic, ethnic and vulnerable groups in the community and if necessary, create strategies to improve participation and compliance. Pilot prostate health checks: 1. Evaluate biopsy rates, early-stage high, intermediate and low risk prostate cancer detection rates and model cost-effectiveness of the different intervention arms. 2. Management of prostate cancer, testing and treatment relative adverse events and side effects. TRANSFORM Discovery: Operationalise TRANSFORM Discovery through optimisation and establishment of a bio-digital twin comprising a trial related tissue collection, multi-omic tissue processing, digital pathology and imaging data matched with clinical data from the main TRANSFORM database. Stage 2: main trial: Long term cancer outcomes: 1. Evaluate prostate cancer mortality and prostate cancer metastases. 2. Evaluate prostate cancer incidence. 3. Biopsy rates, early stage high, intermediate and low risk prostate cancer detection, management of prostate cancer, testing- and treatment-related adverse events and side effects. Costs and cost-effectiveness: 1. Estimate the cost-effectiveness of strategies based on the screening intervention, compared with the current UK standard of care and update these estimates as the trial progresses. 2. Carry out a care pathway analysis and budget impact analysis to determine resource and manpower implications of a screening recommendation within the UK healthcare system. TRANSFORM Discovery: TRANSFORM Discovery will deliver digital data and biospecimen collection from the trial and undertake (i) biomarker testing at scale and pace, (ii) accelerate translational & discovery science, and (iii) establish a sustainable long-term Bio-Digital Twin model. Biomarker testing will be undertaken, with embedded health economic evaluations, to deliver rapid real-time testing of biomarkers in collaboration with academic and commercial partners. TRANSFORM Discovery will facilitate exploratory simulations of novel strategies of healthcare delivery though data modelling to inform development of new hypotheses for prostate cancer management. |
| Ethics approval(s) |
Approved 29/08/2025, Wales REC5 Health and Care Research Wales (Castlebridge 5, Cardiff, CF11 9AB, United Kingdom; +44 (0)2922 940910, 02922 940954, 02922 941106; Wales.REC5@wales.nhs.uk), ref: 25/WA/0197 |
| Health condition(s) or problem(s) studied | Prostate cancer |
| Intervention | In this multi-arm multi-stage randomised platform trial, eligible men will be invited via their GP practice for a community-based screening intervention. The trial will involve two stages. In Stage 1 (pilot), two pre-consent randomisation designs will be evaluated. In Design 1, participants will be approached to express interest in joining the TRANSFORM Research Cohort. Consenting participants will be randomised to one of four screening pathways (“Prostate Health Checks”) or to a control group. Design 2 follows a “Zelen” approach, whereby participants are randomised prior to consent to one of four Prostate Health Checks or to a control. Participants in the control groups in both designs will follow usual care. The aim is to evaluate which method is most feasible in terms of screening uptake to power the main trial (Stage 2), taking into account potential contamination (rates of PSA testing in the control groups) where possible. The optimal trial design and Prostate Health Check will be taken forward to Stage 2 for evaluation on a larger group of men. Stage 1 will incorporate a single screening round and Stage 2 will include at least two rounds of screening. In parallel, the Transform Discovery Biodigital Twin (BDT) will collect biological specimens to guide translational research and real-time assessment of novel biomarkers. |
| Intervention type | Other |
| Primary outcome measure(s) |
Stage 1: Feasibility outcomes |
| Key secondary outcome measure(s) |
Stage 1: feasibility outcomes: |
| Completion date | 01/12/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 45 Years |
| Upper age limit | 74 Years |
| Sex | Male |
| Target sample size at registration | 16000 |
| Key inclusion criteria | Stage 1: 1. Men in the general population aged 50-74 years. 2. Additionally, men aged 45-49 years who self-identify in GP practice lists as of Black ethnicity. 3. Additionally, men aged 45-49 years who are on the GP learning disability Quality Outcome Framework (QOF) register. |
| Key exclusion criteria | 1. History of prostate cancer (clinical diagnosis or histological). 2. Known history of one or more PSA tests, prostate MRI scans, prostate biomarker tests or prostate biopsies in the preceding 5 years. 3. Urinary tract infection in the 3 months before screening. 4. Significant co-morbidities or other cancers likely to impact their life expectancy in the next 10 years. |
| Date of first enrolment | 01/12/2025 |
| Date of final enrolment | 01/06/2027 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centres
St Marys Hospital
South Wharf Road
London
W2 1BL
United Kingdom
London
NW1 2PG
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
24/09/2025: Study's existence confirmed by the NIHR.
