Assessment of intra-individual variation in prostate-specific antigen levels in a biennial randomized prostate cancer screening program in Sweden

BACKGROUND. The degree of variability in prostate-specific antigen (PSA) measurements isimportant for interpreting test results in screening programs, and particularly for interpreting the significance of changes between repeated tests. This study aimed to determine the long-term intra-individual variation for PSA in healthy men. METHODS. A randomly selected cohort of men in a biennial prostate cancer screening program (ERSPC) conducted in Sweden from 1995-1996 to 2001-2002. We studied men who had total PSA (tPSA) levels <2.0 ng/ml in 2001-2002. This included 791 men with tPSA <0.61 ng/ml (group A), 1,542 men with tPSA <0.99 ng/ml (group 13), and 1,029 men with tPSA 1.00-1.99 ng/ml (group Q. The intra-individual variability of free PSA (fPSA) and tPSA was assessed by calculating coefficients of variation (CV) for each individual's PSA measurements from the first and second round of screening (1995-1996 and 1997-1998). RESULTS. Intra-individual CV (geometric means) for tPSA were 13.7%,12.7%, and 11.5% in groups A, B, and C, respectively. Corresponding CVs for fPSA were significantly lower, ranging from 12.1% to 10.4%. The estimated biological variation of tPSA and fPSA in groups A to C were 12.5%,11.4%, 10.0% and 9.7%, 7.8%, 7.5%, respectively. CONCLUSIONS. In healthy men with PSA levels less than 2 ng/ml, the natural long-term variability for tPSA was less than 14%, and with 95% probability, a change in tPSA greater than 30% indicates a change beyond normal random variation.