Integration of the PRODICT test into the prostate cancer risk pathway

Research Question: Can the PRODICT genetic test be implemented into the NHS pathway to risk-stratify a population to effect stage-shift in prostate cancer (PrCa)?

Background: We have developed a new genetic test/product aiming to change and improve the current diagnostic/clinical pathway for PrCa and potentially be used for a National Cancer Screening Programme (NCSP). We have called this test PRODICT. PrCa affects 1 in 6 men1.

There is ~90-100% survival for those diagnosed with stage I/II PrCa (localized, low grade), reducing to 50% for stage IV (metastatic)1. More than 50% of predisposition to PrCa is genetic, (a mixture of common and rarer higher-risk genetic variants)2.

Our team has found >75% of these and recently reported a common variant profile applicable to individuals of multi-ethnic origin3; crucial for the diverse UK population.

The PRODICT test has been developed to stratify people into risk categories based on the combination of these common and rare variants. Our BARCODE1 study used a saliva-based DNA test to calculate a personalized polygenic risk score for PrCa risk4. Preliminary results show enrichment of PrCa detection through targeted screening.

There is currently no UK NCSP for PrCa and while other assessment modalities have been considered, PRODICT would confer several advantages.

BARCODE1 was limited to those of European ancestry, so validation in other groups and extending the test to include common and rare variants, will be key to successful implementation.

Aims Primary: Can PRODICT be integrated into an NHS pathway and does it result in a PrCa detection-stage-shift Secondary: Can PRODICT be widely implemented in people aged 40-55 with prostates (multiethnic-men, non-binary and trans-women) Model introducing PRODICT into primary care and augment a targeted NCSP.

Objectives: To determine: proportion of individuals taking up the programme/number invited proportion of individuals at higher-risk number of raised PSA tests triggering MRI/biopsy number/stage of cancers detected overdiagnosis health economics barriers to implementation evaluation of human factors, challenges and real-world use/performance of the test Methods: Eligible people will be ascertained via GPs and offered the PRODICT (saliva-based DNA) test.

Recruitment target: 1000 (equal numbers from Asian, African and European populations).

People classified as high-risk will be offered PrCa screening (PSA +/- MRI/biopsy) either with: a PRS in the highest 20% of the risk score and/or a rare variant in a gene on the panel Timelines: Pre-Award: Regulatory/ethics approvals Month-4-28: Recruitment Month-36: Screening results published. PRODICT test ready for adoption by NHS and/or commercial provider.

Impact/dissemination: This project will assess whether a genetic test can be successfully implemented within an NCSP.

If successful, more people with PrCa will be identified at an earlier stage, increasing opportunities for curative treatment, enabling more people to live longer and a significant cost-saving for the NHS. There is variable uptake of NCSPs.

By focusing on people from minority ethnic groups and working with stakeholders/public members we will identify barriers and successful means to overcome challenges to implementation.