Integrating genetic testing into the prostate cancer pathway to more precisely guide care, treatment and accelerate clinical trials

Research question: How can the integration of genetic testing within the prostate cancer (PrCa) screening, diagnostic and management pathway improve patient care and be cost efficient for the NHS?

Background: PrCa affects 1-in-8 UK men, has a high mortality rate; considerable morbidity; and is estimated to cost the UK £160m/year.

Early detection of men who will develop aggressive cancers, whilst avoiding over-diagnosis of indolent disease, remains a significant challenge. We have developed and validated a genetic test that detects both common and rare genetic variants.

This programme will inform the implementation of that test into the UK National Genomic Test Directory (NGTD) and demonstrate its utility in the PrCa screening and treatment pathway.

Aims and objectives: To demonstrate germline genetic testing in the PrCa care pathway to improve and inform patient management Methods: Five work packages (WP) will integrate findings from several interlinked projects applying genetic testing within PrCa screening and management.

WP1 is a large prospective cohort-study using a gene panel test in a population of men to identify: (i) those at high-risk; (ii) those at risk of aggressive/lethal PrCa. WP2 will offer targeted screening to men - from WP1 - identified with germline mutations in rare genes.

For those at higher-risk of aggressive PrCa, we will track clinical outcomes (WP3) and offer clinical trials of therapies that precisely target aggressive PrCa.

Qualitative exploration of stakeholder experiences and economic evaluations will consider the impact and benefits of integrating genetics into PrCa screening and management from the perspective of the patient (WP4) and the NHS (WP5). WP4 will determine the information/support requirements of men going through the testing process.

WP5 will evaluate whether a programme of genetic testing, in combination with targeted PrCa screening in unaffected men, will have health benefits for men and whether this would be cost-effective or cost-saving for the NHS.

Timelines for delivery If successful, this research will alter the PrCa screening and treatment pathway within ten years. We aim to generate evidence to support NGTD adoption of the genetic panel test by the programme end. The economic evaluation will be available at the end of the programme. The digital educational resource will be developed and launched by the end of the programme.

Anticipated impact and dissemination By programme completion: 1.Adoption of genetic testing into the NGTD for men with PrCa and guidelines for whom/when to test. 2.Identification of men with genetic variants for targeted treatment, forging pathways into clinical trials, thus speeding up translation of novel therapies. 3.Development of a digital, patient-facing, educational resource package to support implementation. 4.Health economic analysis assessing whether integration of genetic testing into the screening and treatment pathway is cost-effective and where/ when any cost savings could occur in the pathway.

Longer-term Outputs: 1.Precise estimates of each specific PrCa variant and long-term clinical outcomes. 2.National Screening Committee adoption of targeted PrCa screening for unaffected men at higher genetic risk. 3.Report to NICE/the Royal Colleges, Prostate Cancer UK (PCUK), Cancer Research UK (CRUK) on role of targeted therapies guiding management.