Prostate cancer (PCa) is the third most common cancer among men and the fourth leading cause of cancer death in Hong Kong, with incidence steadily increasing over the past four decades.¹ Low screening uptake and high mortality from metastatic PCa further contribute to the overall disease burden.^2,3 A recent cost-effectiveness modeling study led by the University of Hong Kong demonstrated that prostate-specific antigen (PSA) screening in men aged ≥45 years significantly reduces advanced stage disease at diagnosis and lowers mortality.² The study also showed that risk-stratified PCa screening remains cost-effective, supporting its potential role in future cancer prevention and control policies.²

Early PCa is often asymptomatic with many cases detected incidentally.^2,3 The absence of an international consensus on targeted PSA screening for men at increased risk further contributes to low PSA uptake and delayed diagnosis.^2,4 Despite PSA screening reducing disease-specific mortality, its use is frequently limited to high-risk populations or well-informed men who actively seek testing due to concerns about overdiagnosis and unnecessary biopsies.² Consequently, over half of patients present at advanced stages, highlighting the urgent need for earlier detection strategies.⁵ Targeted approaches, such as genetic risk stratification, have been proposed to identify high-risk individuals and refine screening strategies, yet their cost-effectiveness remains uncertain.² This study aims to evaluate the efficacy and cost-effectiveness of multiple PSA screening strategies in China using a dynamic Markov microsimulation model that accounts for population aging.²

The study evaluated 56 population-wide PSA screening strategies in Chinese men, incorporating age, screening interval, and age-specific PSA thresholds, alongside approaches involving genetic risk stratification based on family history, polygenic risk scores (PRS), and high-penetrance gene mutations (HPGs).² Data were drawn from a five-year trial with over 100,000 participants, and a 20-year multicenter database with parameters collected across China.² The model simulated disease onset, progression, detection, treatment, and prognosis over a 30-year horizon, assessing clinical outcomes including PCa incidence, metastasis-incidence ratio (M/I ratio), and annual case-fatality rate (CFR).² Cost-effectiveness was evaluated using incremental quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs).²

The study demonstrated that annual PSA screening for men ≥45 using age-specific PSA threshold can significantly reduce the incidence of advanced-stage PCa from 39.05% to 1.04% and lower the mortality rate from 6.14% to 2.85%.² All screening strategies led to QALY gains and were cost-effective under a willingness-to-pay threshold.² Even the most intensive protocol (45-74 years, annual, age-specific PSA cutoffs) yielded an ICER of USD $5,535.25/QALY, well below China’s per capita gross domestic product (GDP) benchmark (USD $12,510.12/QALY), affirming that periodic PSA screening is highly cost-effective.² Cost-effective interventions in lower-GDP regions may serve as a scalable reference for countries with similar disease burden and socioeconomic conditions, while delivering even greater economic and clinical benefits in higher-resource settings such as Hong Kong (GDP per capita USD $54,074.70 in 2024).^2,6

The study also proposed precision stratification using family history, PRS, and rare pathogenic mutations (RPMs) to tailor screening based on individual genetic risk.² The genetic risk-specific protocol offered comparable QALYs (2.79 vs. 2.76) and ICERs ($5,287.23 vs. $4,904.90 per QALY) to standard population-wide screening, while allowing 66.8% of average-risk individuals to delay the start of screening or extend screening intervals.² This approach maintains overall survival and QALY gains while further improving cost-effectiveness, offering a precision-based alternative to universal screening strategies by tailoring screening intensity across different risk groups.²

In conclusion, PSA screening has the potential to improve health outcomes cost-effectively.² Personalized genetic risk-based strategies can optimize resource use by reducing unnecessary interventions among the lower-risk population.² Drawing on clinical data from both Hong Kong and Mainland China, this study provides robust evidence to support the implementation of a risk-stratified PCa screening program to enable earlier detection and appropriate treatment, extend healthy life expectancy, reduce overdiagnosis and overtreatment, and alleviate both societal and healthcare costs, while supporting more efficient and sustainable PCa management.²