Every year, nearly 50,000 UK men are diagnosed with prostate cancer and over 12,000 die from it, yet routine PSA screening is not recommended because the harms of false positives and over-treatment outweigh the benefits. The TRANSFORM trial will test whether new screening strategies—combining improved PSA testing with modern MRI and biopsy techniques—can tip that balance. The problem is that the old screening approach caught too many harmless cancers while missing some dangerous ones, leading to unnecessary biopsies and anxiety. Since the European trial that showed a 20% relative risk reduction in prostate cancer death, secondary care pathways have changed significantly, potentially reducing the harms of screening. If successful, this trial could establish a cost-effective national screening programme that catches clinically important prostate cancers earlier, reducing rates of metastatic and fatal disease without causing unacceptable harm. The study will also create a biorepository of tissue, imaging, and blood samples for future research. Over three stages—starting with four screening strategies in men aged 50-75 (and Black men aged 45-49), then a pivotal randomised trial, then long-term follow-up through national databases—the researchers will measure biopsy rates, cancer detection by severity, treatment harms, and quality of life.
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Each year in the UK, nearly 50,000 men are diagnosed with, and over 12,000 die from, prostate cancer (PCa). The European screening trial showed that repeat PSA testing reduces the relative risk of dying from PCa by 20%, but with false positives and negatives and over-detection of clinically insignificant cancer with resultant harms of biopsy and treatment. PSA screening has therefore not been recommended because the associated harms outweigh the benefits. There have since been several pivotal changes in the secondary care pathways which have been shown to reduce these harms. The TRANSFORM study will deliver a randomised control trial evaluating new screening strategies in primary care and the community, which improve this therapeutic ratio, coupled with these changes in secondary care. Aims - Deliver a pivotal RCT of novel PCa screening strategies compared to no proactive screening - Demonstrate acceptability, & clinical & cost-effectiveness of screening strategies - Determine barriers/facilitators to ensure equitable engagement - Create a data, imaging, histological & biological sample repository Hypotheses 1. In men 50-75, novel screening strategies, compared to current UK standard of care, will increase the early detection of clinically important PCa such that rates of metastatic/fatal disease are reduced in the long term, without leading to unacceptable rates of biopsy & consequent harms 2. The benefits in earlier detection of PCa will outweigh the potential physical & psychological harms of over-detection/treatment of clinically insignificant disease 3. The new screening strategies will be cost-effective in the UK Methods Stage 1: Will assess 4 screening strategies in a single multi-arm design and determine optimal trial processes and recruitment/randomisation strategies. Men aged 50-75, in addition to men aged 45-49 with Black ethnicity, with no history of PCa, no previous PSA test or MRI scan, PCa biomarker test or prostate biopsy in the preceding 5 years will be asked to participate. Objectives: - Evaluate pre- & post-randomisation consent designs in terms of screening uptake & contamination in the control groups - Measure rates of acceptance to an invitation to a screening study & determine effective recruitment approaches - Investigate barriers/facilitators to participation in, & compliance to, screening interventions - Measure rates of contamination in the control groups - Evaluate biopsy rates & early stage clinically significant PCa detection - Establish biobanking protocols & resource requirements Outcome measures: - PROMS on genitourinary, sexual & rectal toxicity following biopsy/treatments - PROMS on anxiety & overall health-related quality of life - Biopsies avoided (compared to a strategy of PSA>3) - Biopsy related harms, incl. rates of infection, sepsis, retention of urine & hospital admissions - Treatment related harms, e.g. infection, hospital admissions, investigations for treatment related symptoms, interventions for complications & death - The distribution of detection by Gleason score & Grade Group (GG) - Rates (& type) of treatment & active surveillance for low risk & separately GG1 disease overall - Rates (& type) of treatment & active surveillance for intermediate risk & GG2 disease stratified by sub-categories of intermediate risk & GG2 disease Stage 2: Involves the pivotal RCT of the most promising screening approach(es) tested in Stage 1 (trial design to be informed by Stage 1). PROMs will be investigated to evaluate health related quality of life. Cost effective analyses and NHS care pathway analyses will be conducted to determine the healthcare resource impact of screening. Fluid/tissue samples and imaging data will also be collated and stored to establish a biorepository. Stage 3: Will follow up trial participants through national database linkage, reporting longer-term outcomes from screening. Outcomes & Impact It is expected that this study will show a reduction in advanced/metastat
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