Variation of Serum Prostate-Specific Antigen Levels

Objective To determine whether year-to-year fluctuations in PSA levels are due to natural variation and render a single PSA test result unreliable. Design, Setting, and Participants Retrospective analysis of an unscreened population of 972 men (median age, 62 years) participating in the Polyp Prevention Trial (1991-1998). Five consecutive blood samples were obtained during a 4-year period and were assessed for total and free PSA levels. Main Outcome Measure Abnormal PSA test result based on a PSA level higher than 4 ng/mL; a PSA level higher than 2.5 ng/mL; a PSA level above the age-specific cutoff; a PSA level in the range of 4 to 10 ng/mL and a free-to-total ratio of less than 0.25 ng/mL; or a PSA velocity higher than 0.75 ng/mL per year. Results Prostate biopsy would have been recommended in 207 participants (21%) with a PSA level higher than 4 ng/mL; in 358 (37%) with a level higher than 2.5 ng/mL; in 172 (18%) with a level above the age-specific cutoff; in 190 (20%) with a level between 4 and 10 ng/mL and a free-to-total ratio of less than 0.25 ng/mL; and in 145 (15%) with a velocity higher than 0.75 ng/mL per year. Among men with an abnormal PSA finding, a high proportion had a normal PSA finding at 1 or more subsequent visits during 4-year follow-up: 68 (44%) of 154 participants with a PSA level higher than 4 ng/mL; 116 (40%) of 291 had a level higher than 2.5 ng/mL; 64 (55%) of 117 had an elevated level above the age-specific cutoff; and 76 (53%) of 143 had a level between 4 and 10 ng/mL and a free-to-total ratio of less than 0.25 ng/mL. Conclusion An isolated elevation in PSA level should be confirmed several weeks later before proceeding with further testing, including prostate biopsy.