Lifetime Benefits and Harms of Prostate-Specific Antigen-Based Risk-Stratified Screening for Prostate Cancer

Abstract

Background: Studies conducted in Swedish populations have shown that men with lowest prostate-specific antigen (PSA) levels at ages 44-50 years and 60 years have very low risk of future distant metastasis or death from prostate cancer. This study investigates benefits and harms of screening strategies stratified by PSA levels.

Methods: PSA levels and diagnosis patterns from two microsimulation models of prostate cancer progression, detection, and mortality were compared against results of the Malmö Preventive Project, which stored serum and tracked subsequent prostate cancer diagnoses for 25 years. The models predicted the harms (tests and overdiagnoses) and benefits (lives saved and life-years gained) of PSA-stratified screening strategies compared with biennial screening from age 45 years to age 69 years.

Results: Compared with biennial screening for ages 45-69 years, lengthening screening intervals for men with PSA less than 1.0 ng/mL at age 45 years led to 46.8-47.0% fewer tests (range between models), 0.9-2.1% fewer overdiagnoses, and 3.1-3.8% fewer lives saved. Stopping screening when PSA was less than 1.0 ng/mL at age 60 years and older led to 12.8-16.0% fewer tests, 5.0-24.0% fewer overdiagnoses, and 5.0-13.1% fewer lives saved. Differences in model results can be partially explained by differences in assumptions about the link between PSA growth and the risk of disease progression.

Conclusion: Relative to a biennial screening strategy, PSA-stratified screening strategies investigated in this study substantially reduced the testing burden and modestly reduced overdiagnosis while preserving most lives saved. Further research is needed to clarify the link between PSA growth and disease progression.

Figure 1.

The structures of the Fred Hutchinson Cancer Research Center (FHCRC) model and the Erasmus University Medical Center-MIcrosimulation SCreening ANalysis (Erasmus-MISCAN) model. PSA = prostate-specific antigen.

Figure 2.

Observed prostate-specific antigen (PSA) distributions and predicted 25-year risk of diagnosis based on empirical data from the Malmö Preventive Project (N = 10 357) and corresponding model projections in the absence of screening for men ages 44–50 years. Both empirical and model projections are derived from logistic regression models for event of disease diagnosis over 25 years in either the empirical or the modeled data. Erasmus-MISCAN = Erasmus University Medical Center-MIcrosimulation SCreening ANalysis; FHCRC = Fred Hutchinson Cancer Research Center.

Figure 3.

Observed prostate-specific antigen (PSA) distributions and predicted 25-year risk of diagnosis based on empirical data from the Malmö Preventive Project (N = 1162) and corresponding model projections in the absence of screening for men aged 60 years. Both empirical and model projections are derived from logistic regression models for event of disease diagnosis over 25 years in either the empirical or the modeled data. Erasmus-MISCAN = Erasmus University Medical Center-MIcrosimulation SCreening ANalysis; FHCRC = Fred Hutchinson Cancer Research Center.