Modelling the potential contributions of polygenic risk stratification to cost-effective screening for prostate cancer

Background Prostate cancer (PCa) is one of the most common cancers globally. The potential for polygenic risk scores (PRSs) to improve risk stratification for early detection of PCA in screening interventions is of considerable interest. We evaluated the cost-effectiveness of PRS-guided screening strategies. Methods The Prostata microsimulation model, calibrated to UK-specific epidemiological and clinical data, simulated individual life histories, including disease onset and progression, tumour characteristics by Gleason score, and metastatic status. The model incorporated both measured and unmeasured components of polygenic risk for incident PCa, and included ancestry-specific strata. Screening strategies were compared against a no-screening baseline. We modelled one-off, age-based prostate specific antigen screening at 50, 60, or 70 years, as well as repeated uniform screening every 4 or 2 years from age 50 to 69 with and without PRS stratification. Results Quality-adjusted life years were similar across all screening strategies, while differences in costs were more pronounced. A "no screening" strategy had the lowest lifetime cost of all strategies and (very marginally) the shortest life expectancy. Realistic PRS implementations were dominated (less effective and more expensive) in all scenarios, and may not provide greater cost-effectiveness than a single PSA screen at age 50 or compared to no screening at all. Conclusion Our study found little evidence that PRSs would be cost-effective in pragmatic PCa screening settings.