Overdiagnosis and Lives Saved by Reflex Testing Men With Intermediate Prostate-Specific Antigen Levels

Area of Science:

• Urology
• Oncology
• Health Services Research

Background:

• Prostate cancer (PCa) early detection relies on biomarkers for men with intermediate prostate-specific antigen (PSA) levels.
• Existing studies focus on diagnostic performance, neglecting overdiagnosis and lives saved, crucial for assessing harm and benefit.

Purpose of the Study:

• To project overdiagnoses and lives saved from using urinary reflex biomarkers for PCa screening.
• To evaluate the impact of current and hypothetical ideal biomarkers on PCa screening outcomes.

Main Methods:

• Utilized a microsimulation model of PCa incidence and mortality.
• Assessed four urinary reflex biomarkers and two hypothetical ideal biomarkers (100% sensitivity/specificity) in 1112 men aged 55 and 65.
• Modeled one-time screening tests and continued screening scenarios.

Main Results:

• Reflex testing reduced overdiagnoses (8.8-60.6%) and lives saved (7.3-64.9%) compared to biopsying all men with elevated PSA, maintaining a similar ratio.
• An ideal biomarker for high-grade PCa improved the overdiagnosis-to-lives-saved ratio by 35.2% (age 55) and 42.0% (age 65).
• Incremental benefits of the ideal biomarker were smaller under continued screening scenarios.

Conclusions:

• Modeling demonstrates the utility of reflex biomarkers in projecting long-term PCa outcomes.
• Urinary reflex biomarkers are expected to reduce overdiagnoses and lives saved commensurately.
• Targeting high-grade PCa with accurate reflex testing can enhance the net benefit of prostate cancer screening.