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

Abstract Background Prostate cancer (PCa) remains one of the most commonly diagnosed cancers worldwide. The use of polygenic risk scores (PRSs) to enhance individual risk stratification and guide early detection strategies has attracted growing research and policy interest. We assessed the cost-effectiveness of PRS-guided screening strategies for PCa within a UK context. Methods The Prostata microsimulation model, calibrated to UK-specific epidemiological and clinical data, simulated individual life histories, including PCa onset, progression, and outcomes by Gleason score and metastatic status. The model incorporated both measured and unmeasured components of polygenic risk and accounted for ancestry-specific distributions. We compared a no-screening baseline with one-off prostate-specific antigen (PSA) screening at ages 50, 60, or 70, and with repeated uniform screening every 4 or 2 years between ages 50 and 69, both with and without PRS-based stratification. Results Quality-adjusted life-years (QALYs) were similar across all strategies, while costs differed more substantially. The no-screening scenario yielded the lowest lifetime costs and marginally lower life expectancy. PRS-informed strategies were dominated, being more costly and less effective than alternatives. Conclusion PRS-guided PCa screening was unlikely to be cost-effective in modelled scenarios compared with either no screening or simple age-based PSA testing.