Polygenic risk-tailored screening for prostate cancer: A benefit-harm and cost-effectiveness modelling study

Area of Science:

• Oncology
• Health Economics
• Preventive Medicine

Background:

• The United States Preventive Services Task Force recommends individualized decisions for prostate-specific antigen (PSA) screening in men aged 55-69.
• Understanding how screening benefits and harms vary by individual risk is crucial for informed decision-making.
• This study models the trade-offs of risk-tailored screening versus age-based and no screening.

Purpose of the Study:

• To examine the benefit-harm tradeoffs of a risk-tailored prostate cancer screening program.
• To evaluate the cost-effectiveness of risk-tailored screening compared to age-based and no screening.
• To inform decision-making for prostate cancer screening at individual and population levels.

Main Methods:

• A life-table model projected prostate cancer incidence and mortality in a hypothetical cohort of 4.48 million English men aged 55-69.
• Compared no screening, age-based screening (quadrennial PSA testing), and risk-tailored screening based on a 10-year absolute risk threshold.
• Analyzed costs from a health service perspective, including risk assessment, screening, diagnosis, and treatment, using probabilistic sensitivity analyses.

Main Results:

• Age-based screening prevented the most deaths but resulted in the highest number of overdiagnosed cancers and was the least cost-effective.
• Risk-based screening at a 4% 10-year absolute risk threshold generated the most quality-adjusted life-years (QALYs).
• Risk-based screening led to one-third fewer overdiagnosed cancers than age-based screening, while averting 6.3% fewer deaths.

Conclusions:

• Offering prostate cancer screening to men at higher risk may reduce overdiagnosis and improve the benefit-harm tradeoff.
• Risk-tailored screening demonstrates improved cost-effectiveness compared to age-based strategies.
• The optimal risk threshold for screening depends on societal judgments regarding benefits, harms, and cost-effectiveness.