Trial of Randomised Approaches for National Screening FOR Men (TRANSFORM)

ISRCTN	ISRCTN13801649
DOI	https://doi.org/10.1186/ISRCTN13801649
IRAS number	343441
Secondary identifying numbers	CPMS 57097, Grant Code: MA-BD22-001

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

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

Mrs Natalia Klimowska-Nassar
Scientific

-
-
-
United Kingdom

Email	n.klimowska@imperial.ac.uk

Prof Hashim Ahmed
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
Email	hashim.ahmed@imperial.ac.uk

Ms Francesca Rawlins
Scientific

Imperial College London
B Block
Hammersmith Hospital
Du Cane Road
London
W12 0NN
United Kingdom

Phone	+44 (0)20 7594 1660
Email	f.rawlins@imperial.ac.uk

Study information

Study design	Randomized controlled study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Community, GP practice, Hospital
Study type	Screening
Participant information sheet	Not available in web format, please use the contact details to request a patient 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	Stage 1: Feasibility outcomes 1. Proportion who receive the Prostate Health Check (PHC) in each screening intervention arm (Design 1 and Design 2, separately) at the end of the trial 2. Proportion with PSA test in each of the control groups (Design 1 and Design 2, separately) measured through linkage to national databases at the end of the trial Stage 1: Prostate health checks intervention pilot outcomes In each PHC group: 1. Proportion diagnosed with intermediate-risk prostate cancers (NCCN) [also collected in control groups] at the end of the trial 2. Proportion diagnosed with low-risk prostate cancers (NCCN) [also collected in control groups] at the end of the trial 3. Proportion having a prostate biopsy [also collected in control groups] at the end of the trial 4. Costs and cost-effectiveness modelling of each PHC intervention (from first visit to diagnosis/treatment)
Secondary outcome measures	Stage 1: feasibility outcomes: 1. Proportion who provide Stage 1 consent (Design 1) 2. Proportion with Black ethnicity invited (Designs 1 and 2 combined) 3. Cost per successful consent (Design 1 and Design 2 separately): 4. Proportion who provide Stage 1 consent (Design 1) by age group, ethnicity, IMD quintile 5. Proportion of men with learning disability or severe mental illness who provide Stage 1 consent (Design 1) 6. Proportion undergoing PHCs in each screening intervention arm by age, ethnicity, IMD quintile (Design 1) 7. Performance indicators, including compliance with further assessment and compliance with treatment Stage 1: prostate health checks intervention pilot outcomes: In each randomised PHC group: Timelines: Time (days) from randomisation to a) undergoing the first part of each PHC to b) receiving the result of the first test to c) undergoing Prostagram™ to d) receiving the result of the Prostagram™ to e) having a prostate biopsy in those advised to undergo a prostate biopsy Detection: 1. Proportion diagnosed with high-risk prostate cancers (NCCN) 2. Proportion diagnosed with low/intermediate/high-risk prostate cancer according to NICE risk groups (* based on Cambridge Prognostic Group, low-risk = CPG1, intermediate-risk = CPG2-3, high-risk = CPG4-5, ref: ww.nice.org.uk/guidance/ng131) 3. Proportion diagnosed by ISUP Grade Group: GG1, GG2, GG3, GG4, GG5 prostate cancer 4. Proportion diagnosed by T stage 5. Proportion diagnosed with any amount of Gleason 4+3=7 or more 6. Proportion diagnosed with ≥ Gleason 4+3 OR Gleason 3+3=6 of ≥6mm (PROMIS definition 1) 7. Proportion diagnosed with ≥ Gleason 3+4 OR Gleason 3+3=6 of ≥4mm (PROMIS definition 2) 8. Proportion of GG2 cancers in each of the following categories of percentage pattern 4 involvement: ≤10%, 11-20%, 21-30%, 31-40%, 41-50% In those diagnosed with prostate cancer: 1. Maximum cancer length on biopsy in millimetres 2. Gleason Score Ratio of GS6 to GS7+ 3. Proportion with lymph node cancer involvement of the pelvis (N1) only 4. Proportion with distant / metastatic disease by individual stage categories: distant lymph nodes (M1a), bones (M1b) and organs such as the liver, brain or lungs (M1c) stratified by N0 or N1 status NCCN Guidelines Version 4 (2024)59 will be used to define prostate cancer risk groups where indicated. Biopsy-related harms: 1. Biopsy-related harms measured by PROBE questionnaire score 2. Proportion with culture-proven infection related to biopsy/within 90 days of biopsy 3. Proportion with infection treated with antibiotics (in the absence of culture confirmation) related to biopsy/within 90 days of biopsy 4. Proportion with sepsis related to biopsy/within 90 days of biopsy 5. Proportion with urinary retention requiring catheterisation (permanent or intermittent) related to biopsy/within 90 days of biopsy 6. Proportion with bleeding requiring catheterisation or hospital admission related to biopsy/within 90 days of biopsy 7. Proportion with vasovagal episode requiring hospital review or admission related to biopsy/within 90 days of biopsy 8. Proportion whose death is related to biopsy/within 90 days of biopsy 9. Rate of hospital admissions within 90 days after biopsy Treatment: 1. Proportion receiving active surveillance, focal therapy, prostatectomy, and radiotherapy (with and without ADT) as first option by low, intermediate and high-risk disease subgroups (NCCN). Proportion having ADT and type of ADT as monotherapy to be reported. 2. Proportion receiving active surveillance, focal therapy, prostatectomy and radiotherapy (with and without ADT) as first option by low, intermediate and high-risk disease subgroups (NICE risk groups). Proportion having ADT and type of ADT as monotherapy to be reported. 3. Proportion receiving active surveillance, focal therapy, prostatectomy and radiotherapy (with and without ADT) as first option by ISUP Grade Groups (GG1, GG2, GG3, GG4, GG5). Proportion having ADT and type of ADT as monotherapy to be reported. 4. Proportion receiving active surveillance, focal therapy, prostatectomy and radiotherapy (with and without ADT) as first option by T stage. Proportion having ADT and type of ADT as monotherapy to be reported. 5. In those diagnosed with ISUP GG2 prostate cancer, proportion receiving active surveillance, focal therapy, prostatectomy and radiotherapy (with and without ADT) as first option by pattern 4 percentage categories (≤10%, 11-20%, 21-30%, 31-40%, 41-50%). Proportion having ADT and type of ADT as monotherapy to be reported. 6. In men undergoing active surveillance, proportion who progress on biopsy or on imaging. 7. In men undergoing active surveillance, proportion who go on to receive focal therapy, prostatectomy and radiotherapy. Proportion having ADT and type of ADT as monotherapy to be reported. 8. In each of the following categories of stage of disease, proportions of type of local prostate treatment by focal therapy, surgery, radiotherapy and type of systemic treatment: ADT, chemotherapy, androgen receptor inhibitors (ARIs), other drugs for prostate cancer treatment and type of treatment directed at distant disease. NB: Breakdown of type of modality used for focal therapy to be collated. NB: Radiotherapy will be divided into numbers undergoing external beam radiotherapy, external beam radiotherapy with neoadjuvant ADT, external beam radiotherapy with adjuvant ADT (and duration), low dose rate brachytherapy and combination radiotherapy (high dose rate or low dose rate brachytherapy combined with external beam radiotherapy and ADT). Numbers undergoing proton therapy and stereotactic ablative radiotherapy (SABR) will also be collected. Treatment-related harms: 1. Rate of hospital admissions within 90 days after treatment 2. Focal therapy-related harms graded by Clavien-Dindo severity category 3. Surgery-related harms graded by Clavien-Dindo severity category 4. Radiotherapy-related harms graded by CTCAE severity category 5. Other treatment-related harms graded by CTCAE severity category 6. Investigations/ tests for treatment related symptoms, interventions for complications, death Patient reported outcome measures (PROMS): 1. PROMS on urinary, sexual and bowel function measured by EPIC-26 Short Form 2. Prostagram Questionnaire – all participants who received an MRI 3. PROBE – adapted for Specification, Perceptions and General questionnaires 4. In participants from sexual minority group, Sexual Minorities and Prostate Cancer Scale (SMACS)61 5. Health Service Use (in draft) 6. Health related quality of life measured by EQ-5D-5L 7. For participants with mild or moderate learning disability, the modified version of EQ-5D-3L62 Learning Difficulty and for those with severe learning disability, the proxy (informant) version 2 of the EQ-5D-5L 8. Demographics Questionnaire 9. Health Behaviour and Family History Questionnaire 10. Anxiety measured by the GAD-7 and Cancer Worry Scale (CWS) adapted to prostate cancer 11. Health Literacy measured by the SILS 12. Risk perception of developing prostate cancer measured on 4 items 13. Acceptability of the received prostate health check measured (prospectively and retrospectively) on the TFA Questionnaire 14. Participant Satisfaction Measure Questionnaire Health economics: 1. Proportion using health services 2. Costs falling on men and their families TRANSFORM Discovery BDT: 1. Define and initiate first wave biomarker validations 2. Define consent rates to TRANSFORM Discovery and metrics of tissue (including quality assurance of biological measures), digital pathology, imaging collection and integration with clinical data.
Overall study start date	01/05/2024
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 number of participants	Stage 1: 16,000; Design 1: 12,500 (2,500 undergoing each PHC, 2,500 randomised to control); Design 2: 3,500 (250 invited to each PHC, 2,500 randomised to control); Stage 2: To be determined based on selected primary outcome, uptake, and outcomes from Stage 1. Likely to be between 180,000 and 500,000 men invited.
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

England
United Kingdom

Study participating centres

Imperial College Healthcare NHS Trust

The Bays
St Marys Hospital
South Wharf Road
London
W2 1BL
United Kingdom

University College London Hospitals NHS Foundation Trust

250 Euston Road
London
NW1 2PG
United Kingdom

Sponsor information

Imperial College London
University/education

Faculty Building
London
SW7 2AZ
England
United Kingdom

Phone	+44 (0)20 7594 9459
Email	r.nicholson@imperial.ac.uk
Website	https://www.imperial.ac.uk
"ROR"	https://ror.org/041kmwe10

Funders

Funder type

Charity

Prostate Cancer UK
Private sector organisation / Other non-profit organizations

Alternative name(s): Prostate Cancer, Prostate Action, ProstateUK, prostatecanceruk
Location: United Kingdom

National Institute for Health and Care Research

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	Results of the trial will be shared with the National Screening Committee in the UK to ascertain whether or not the screening interventions evaluated in TRANSFORM could be implemented within a formal screening programme. Publication of Stage 1 outcomes in peer-reviewed scientific journals is planned. Stage 2 outcomes will be reported at pre-specified timepoints when follow-up data becomes available.
IPD sharing plan	The data-sharing plans for the current study are unknown and will be made available at a later date

Editorial Notes

24/09/2025: Study's existence confirmed by the NIHR.