Cancer Prevention Trials Unit

BEST4 Platform: Barrett’s oESophagus Trial 4  

Oesophageal adenocarcinoma (OAC) has very poor survival outcomes, largely because most cases are detected at a late stage. Its precursor, Barrett’s oesophagus (BO), remains under‑diagnosed due to reliance on endoscopy. 

The BEST4 platform aims to transform early detection and prevention of BO and OAC. It includes Heartburn Health, a major new bio-resource, that will recruit individuals with gastro‑oesophageal reflux disease (GORD) to support future research into BO detection, OAC prevention, and clinical management. 

The platform includes two clinical trials: 

BEST4 Screening Trial: A Randomised Controlled Trial Comparing capsule sponge Test Screening to Usual Care 

A less invasive and more affordable alternative to endoscopy is required to screen at-risk populations and improve early BO detection.  

BEST4 Screening is a large, community‑based randomised controlled trial (N=120,000) evaluating whether offering a capsule sponge test to people taking heartburn medication can increase the detection of BO and reduce the incidence and mortality associated with late-stage OAC. 

Participants are randomised 1:2 to capsule sponge screening or usual care. Screening is delivered through Mobile Diagnostic Units, and those offered the test undergo assessment for BO‑related cellular changes using a capsule sponge. Long‑term outcomes – including new cancer diagnoses, progression, and mortality - will be tracked via national registry data for up to 12 years. 

BEST4 Surveillance Trial: A prospective cohort Trial for the Surveillance of Barrett’s oesophagus using a capsule sponge test and biomarker panel 

A complementary trial evaluating whether Cytosponge‑based surveillance, combined with biomarker testing, can safely replace endoscopy for monitoring individuals with non‑dysplastic BO. Around 1,900 participants will receive Cytosponge surveillance to determine whether future endoscopies can be avoided without compromising safety. 

Both BEST4 Screening and BEST4 Surveillance are open and recruiting.

For further information, please refer to the BEST4 website.

FINESSE: FINasteride Evaluation in active Surveillance for low and intermediate risk prostate cancer 

Many men diagnosed through PSA testing receive radical treatment for cancers that are low or intermediate risk, even though active surveillance (AS) can safely avoid overtreatment. However, PSA fluctuations - often caused by benign prostate changes - can undermine confidence in surveillance and lead to unnecessary intervention. Finasteride, by stabilising PSA levels, may help men remain on active surveillance for longer while supporting safe, evidence‑based decision‑making. 

FINESSE is a multi-centre Phase III randomised controlled trial evaluating whether adding finasteride to active surveillance can increase adherence without disease progression in men with low‑ or intermediate‑risk prostate cancer. The study also assesses whether finasteride can reduce true cancer progression compared with surveillance alone 

More than 227 men aged 50–75 will be randomised to active surveillance alone or with finasteride for two years, with follow‑up for up to five years. 

Supported by: Yorkshire Cancer Research (YCR) 

For further information, please refer to the FINESSE website.

YORKSURe: Early detection of bladder cancer in Yorkshire: Feasibility assessments for implementing a targeted study in populations with high disease-specific mortality risk 

Bladder cancer incidence and mortality are notably higher in Yorkshire than in most other parts of the UK, and many cases are diagnosed late. Earlier detection in high‑risk communities could shift diagnoses to earlier stages, improve survival, and potentially offer a cost‑effective approach to reducing regional inequalities. 

YORKSURe is a prospective, multicohort feasibility study evaluating whether home urine self‑testing for haematuria can support earlier diagnosis of bladder cancer in populations at elevated risk. The study included three cohorts: Cohort 1, comprising participants from the Yorkshire Lung Screening Trial (YLST); Cohort 2, involving adults from high‑mortality communities identified through GP practices and allocated using a randomised conceal/reveal design; and Cohort 3, consisting of NHS patients already referred on the 2‑Week‑Wait (2WW) haematuria pathway. 

Participants completed a six‑day home urine self‑test, and those with positive results were invited to a local Early Detection Clinic for non‑invasive assessments (ultrasound and urine cytology). Only participants with concerning findings were referred to urology services for further specialist investigation. 

YORKSURe assessed feasibility, participant compliance, acceptability, and pathway performance, laying the groundwork for a potential large‑scale (Phase III) early detection trial aimed at reducing bladder cancer mortality in high‑risk regions. 

Status: Recruitment complete; passive follow‑up ongoing. 

Supported by: Yorkshire Cancer Research (YCR)

NHS-Galleri: A randomized, controlled trial to assess the clinical utility of a multi-cancer early detection (MCED) test for population screening in the United Kingdom (UK) when added to standard of care 

Early‑stage cancer diagnosis dramatically improves survival. Galleri’s MCED test can detect signals from multiple cancer types using a single blood sample. Evaluating its performance alongside standard NHS care is essential to determine its clinical utility, benefits and potential harms in population screening.  

NHS‑Galleri is the first UK randomised controlled trial statistically powered to assess the real‑world performance and clinical utility of an MCED test in a population‑level screening setting. 

This large, prospective population‑based RCT (N=142,000) randomised participants 1:1 to either MCED testing or control. Those in the intervention arm were provided a blood sample for MCED analysis; participants with a positive MCED result were referred to NHS urgent investigation pathways. All participants were followed for approximately two years, with additional long‑term follow‑up for cancer diagnoses and outcomes via NHS registry linkages for up to six years 

Status: Dissemination and further analysis ongoing. 

Supported by: GRAIL 

For further information, please refer to the NHS Galleri website.

YouScreen: A pragmatic implementation feasibility clinical trial of offering HPV self-sampling to cervical screening non-attenders within the NHS cervical screening programme in England 

YouScreen addressed declining cervical screening coverage in Northeast and North Central London, where practical and personal barriers have contributed to persistent inequalities. 

This pragmatic feasibility trial integrated HPV self‑sampling into the NHS Cervical Screening Programme for the first time. Over 27,000 self‑sampling kits were distributed across 133 GP practices, with more than 8,000 returned. Published findings in The Lancet showed that postal and opportunistic offering in primary care could substantially increase coverage—potentially reaching an additional 400,000 women per year in England. 

Status: Passive follow‑up ongoing. 

Supported by: NHS North Central London (NCL) and NHS North East London (NEL) Cancer Alliances.

DETECT-2: Direct to Patient testing at Cancer diagnosis for Precision Prevention-2 

Most genetic testing relies on hospital‑based counselling, which is resource‑intensive and difficult to scale for universal testing of all cancer patients. DETECT‑2 is evaluating whether a direct‑to‑patient (DTP) pathway for genetic testing at the time of endometrial, colorectal, or ovarian cancer diagnosis can improve access and be as effective as traditional clinician‑led approaches. 

The DTP pathway provides information through a web‑based decision aid and optional helpline, enables saliva‑based testing at home, and returns results without a clinic visit - offering a more convenient and scalable alternative to hospital‑based pathways. 

DETECT‑2 is a randomised controlled trial comparing the DTP pathway with the standard NHS “mainstreaming” model. Outcomes include testing update, patient experience, psychological wellbeing, quality of life, and cost‑effectiveness. 

The trial will recruit 626 - 832 participants, with an additional qualitative sub‑study involving 36 - 48 participants. Follow‑up questionnaires will be completed for up to one year after consent. 

Status: Recruitment underway. 

Supported by: The North East London Cancer Alliance and GSK

SPOTLIGHT: Understanding the impact of heartburn on health, wellbeing and quality of life 

As BEST4 evaluates clinical outcomes, it is equally important to understand the psychological and behavioural effects of capsule sponge screening. Although around 7% of screened participants may be diagnosed with non‑dysplastic Barrett’s oesophagus (NDB), only 3–13% of that group will progress to dysplasia or oesophageal adenocarcinoma (OAC). SPOTLIGHT focuses on whether screening introduces any positive or negative psychosocial effects, particularly for those diagnosed with NDB—an essential consideration before wider rollout of the test. 

SPOTLIGHT is a nested study within the BEST4 Platform, designed to examine the emotional, behavioural, and wellbeing impacts of taking part in capsule sponge screening. The study aims to determine whether there are long‑term differences in anxiety, cancer worry, and quality of life between participants diagnosed with NDB in the screening arm and those in the control arm who were not offered screening. 

More than 6,000 participants across four groups (control; normal results; abnormal results without Barrett’s; abnormal results with Barrett’s/OAC) will complete surveys over one year to assess wellbeing, anxiety, cancer worry, and screening acceptability. 

Findings will guide how OAC/BO screening is implemented in future programmes, ensuring psychological outcomes are considered alongside clinical benefit. 

Status: Recruiting 

Supported by: Cancer Research UK (CRUK)

PRUDENT: Pathway for Recurrent Urinary infections for early DetectioN of Bladder cancer: a feasibility Trial 

Bladder cancer is often missed in people with recurrent UTIs because both conditions share similar symptoms, causing cancer warning signs to be mistaken for infection. Early diagnosis is crucial for improving survival, yet delays are common and outcomes disproportionately worse in socially deprived and underserved communities. 

PRUDENT is a feasibility study assessing whether home molecular urine testing (Galeas Bladder) can identify people at higher risk of bladder cancer earlier. Electronic searches of GP records in Sheffield, Leeds and Northeast London will identify adults aged 60+ with recurrent UTIs, who will be invited to complete the test at home. Those with abnormal results will be referred via the NHS urgent cancer pathway, with interviews conducted to understand acceptability among patients and clinicians. 

PRUDENT will evaluate feasibility, pathway adherence and acceptability, informing a future, larger Phase III trial. 

Status: In set‑up (from June 2026) 

Supported by: Yorkshire Cancer Research (YCR)

GP-TEST-PRO: Modernising General Practice Testing for the Detection of Clinically Significant Prostate Cancer. 

PSA remains the only diagnostic test available in primary care for prostate cancer, yet its accuracy in symptomatic patients is limited. More advanced approaches - such as polygenic risk scores (PRS) and bi‑parametric MRI (bpMRI)- may offer greater diagnostic precision and reduce the number of patients diagnosed at later stages. 

GP‑TEST‑PRO is a prospective diagnostic cohort study designed to improve early detection of prostate cancer in symptomatic adults with a prostate. The study will directly compare the diagnostic performance of PSA, bpMRI, and a polygenic risk score, either individually or in combination. 

Eligible participants will be identified through GP practices when they present with new lower urinary tract symptoms. Participants will attend a single diagnostic clinic visit for PSA testing, PRS sampling, and bpMRI. Any positive test result will trigger referral via the NHS urgent suspected cancer pathway. All participants will be followed for 12 months to assess diagnostic accuracy and clinical outcomes. 

Status: In set‑up; recruitment from April 2027 

Supported by: NIHR MRC‑EME Academic Fellowship 

IMProVE: Imaging for Prostate cancer screening: Value and Efficacy 

Prostate cancer poses a significant health burden in Yorkshire, where rates of late diagnosis and mortality exceed national averages. Advances in diagnostic imaging now offer the potential for more accurate and safer prostate cancer screening than traditional PSA‑based approaches alone. 

IMProVE is a pilot feasibility study designed to test a modern, risk‑adapted screening strategy that combines PSA testing with imaging, and to determine the most effective invitation methods for large‑scale community engagement. The study will generate key data to inform the design, sample size, and operational approach for a future Phase III prostate cancer screening trial in Yorkshire. 

Up to 45,000 adults with a prostate aged 50–69 will be invited using five randomly allocated outreach methods as part of a Study Within a Trial (SWAT). Participants will attend community‑based mobile clinics for PSA testing and optional polygenic risk score (PRS) sampling. Those who take part will then be randomised to one of two pathways: a stratified, image‑guided screening pathway, or the current NHS PSA‑based pathway for diagnostic decision‑making. 

Findings from IMProVE will evaluate feasibility, recruitment, community testing approaches, and diagnostic yield. These results will determine whether a full‑scale Phase III trial is warranted and how it should be optimally designed. 

Status: In set‑up; recruitment from January 2026 

Supported by: Yorkshire Cancer Research (YCR)

TransPRIDE: Trans and Non-binary Prostate-Specific Antigen Reference Interval Determination Study 

The prostate-specific antigen (PSA) test helps diagnose prostate conditions, including cancer. Current PSA thresholds are based on cisgender men and may not be suitable for trans and non-binary people with a prostate (TNBPP), especially those receiving gender‑affirming hormone therapy (GAHT) or who have had a bilateral orchidectomy.  

These treatments can lower PSA levels, but there is little data on what “normal” PSA looks like for this group. This lack of evidence creates a risk of missed diagnoses and unnecessary investigations. 

TransPRIDE aims to establish age‑related PSA reference intervals for TNBPP on GAHT and/or post‑orchidectomy, helping to reduce health inequalities and improve inclusive prostate care. 

The study will recruit 500 participants, collecting a single blood sample plus demographic and medical information via questionnaire, followed by a six‑month telephone check‑in. 

Status: Currently in set-up. 

Supported by: Prostate Cancer UK (PCUK) 

Protect-C: Population Based Germline Testing for Early Detection and Prevention of Cancer  

More than 700,000 people in the UK are at increased risk of breast, ovarian, womb, or bowel cancer. Currently, NHS genetic testing is only offered to individuals who meet specific criteria—typically those with certain cancers or a strong family history. This approach misses 50–80% of people who carry increased cancer risk, meaning many cannot access early detection or risk‑reducing options. 

Protect‑C is a prospective cohort study evaluating the impact of offering genetic testing to the general population. The study will assess how population-based testing improves identification of high‑ and moderate‑penetrance cancer susceptibility genes (CSGs) and how incorporating common genetic variants can better identify women at moderate/high risk of breast and ovarian cancer. It will also explore the effects on health behaviours, psychosocial outcomes, screening uptake, prevention, and cost-effectiveness. 

The study will recruit 5,000 participants through self‑referral and invitations sent via NHS DigiTrials. Participants will receive a saliva collection kit for genetic testing, and will use a bespoke app for enrolment, consent, and return of results. Follow‑up will continue for two years. 

Status: Currently in set-up. 

Supported by: Yorkshire Cancer Research (YCR)