Abstract
BACKGROUND: The significance of prostate-specific antigen (PSA) in reducing the health burden of prostate cancer is widely deliberated. We conducted this study, utilising real-world data, to develop a comprehensive, cost-effectiveness analysis model for PSA screening. By evaluating various screening strategies, we aim to provide policymakers with robust research evidence to inform future PSA screening policies. METHODS: We constructed a microsimulation model to assess 56 conventional population-wide PSA screening strategies based on data from a five-year trial with 104,751 participants, a 20-year multicentre database and parameters collected across China, along with approaches involving genetic risk stratification based on family history, polygenic risk scores, and high-penetrance genes. Clinical outcomes including incidence, metastasis-incidence ratio (M/I ratio), and annual case-fatality rate (CFR) were evaluated. Cost-effectiveness was evaluated using incremental quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Sensitivity and scenario analyses were conducted to test the robustness of the results. FINDINGS: All strategies led to QALY gains and were considered cost-effective under a willingness-to-pay threshold equal to China's per capita GDP ($12,510.12 per QALY). The most intensive protocol (45-74 years, annually, with age-specific PSA cutoffs) had an ICER of 5535.25USD/QALY, yielding 2.79 incremental QALYs compared to non-screening, reducing M/I ratio from 39.05% to 1.04%, and CFR from 6.14% to 2.85%. The genetic risk-specific protocol offered comparable QALYs (2.79 vs. 2.76) and ICERs (5287.23 vs. 4904.90USD/QALY), allowing for 66.8% of average-risk individuals with extended screening intervals or postponed screening start age. INTERPRETATION: PSA screening in China has the potential to improve overall health outcomes in a cost-effective manner. Personalised screening based on genetic risk may provide an efficient alternative to uniform strategies, potentially reducing unnecessary interventions among those at lower risk. This study provides a solid evidence base for Chinese policymakers to consider establishing a cost-effective, risk-stratified PCa screening programme. FUNDING: Shenzhen-Hong Kong-Macau S&T Programme, HKU Seed Fund, RJH Cultivating Star Programme, HK UGC Research Impact Fund and Guangdong High-Level Talents Programme.