Age-Adjusted Reference Values for Prostate Specific Antigen - A Systematic Review and Meta-Analysis

Objectives: To systematically evaluates the evidence on ethnic differences in age-adjusted reference values of PSA.

Materials and methods: In concordance with the Preferred Reporting Items for Systematic Review and Meta-analysis statement, a review of English articles using Medline, Embase and Cochrane databases, from inception to December 2019 was conducted. Studies that reported the PSA upper reference value as 95th percentile of the cohort distribution, in healthy men aged 40 to 79, were included. Methodological quality was assessed with a modified version of the Agency for Healthcare Research and Quality checklist for cross-sectional studies.

Results: Forty-three studies examining 325,514 participants were included in the analysis. These were published between 1993 and 2018. Majority were prospective observational studies and reported the reference values in ten-year age intervals. Only five reports directly compared ethnic differences in PSA values. Due to missing data, six studies were not considered in the quantitative synthesis. For the remainder (37/43), heterogeneity in PSA reference values was considerable (Higgin's index = 99.2%), with age and ethnicity being the sole identified significant contributors. Accordingly, the pooled upper limits for PSA reference values were 2.1, 3.2, 4.9 and 6.5 ng/ml for men in their 40 s, 50 s, 60 s, and 70 s, respectively.

Conclusion: Moderate quality evidence suggest that upper PSA reference limits increased with age and significant ethnic differences were present.