DERIVATION AND APPLICATION OF UPPER LIMITS FOR PROSTATE-SPECIFIC ANTIGEN IN MEN AGED 50-74 YEARS WITH NO CLINICAL-EVIDENCE OF PROSTATIC-CARCINOMA

Objective To derive age-specific upper limits for prostate specific antigen (PSA) level in men 50-74 years of age with no clinical evidence of prostatic carcinoma, and to test the sensitivity and specificity for cancer detection of these upper limits. Subjects and methods A total of 6166 men were recruited for a multicentre study of prostate cancer detection and underwent a serum PSA determination and digital rectal examination (DRE). Men considered to be clinically free of prostatic carcinoma were those with a normal DRE: and a PSA level less than or equal to 4.0 ng/mL, and men with an abnormality in either parameter who underwent ultrasonography-guided prostate biopsy that revealed no evidence of carcinoma, By these criteria, 5469 men had no evidence of prostatic carcinoma. Dividing the population into 5-year age increments, three statistical methods were assessed to derive upper limits for serum PSA level by age; the mean + 2 SD, the 99th percentile, and a 97.5% prediction interval based on linear regression. Results Newly-derived upper limits calculated by each method in the 50-54 and the 70-74 age group were 3.9 ng/mL, and 7.6 ng/mL (mean + 2 SD), 5.2 ng/mL and 14.0 ng/mL (99th percentile), and 4.7 ng/mL, and 8.2 ng/mL, (97.5% prediction interval), The sensitivity of the newly-derived upper limits was tested using receiver operating characteristic curves derived from men with no suspicious findings on DRE and a serum PSA concentration > 4.0 ng/mL. Although the specificity of the test increased with increasing PSA upper limits, no upper limits derived from these three methods yielded adequate sensitivity to detect cancer; sensitivities by age range were from 53 to 94%, using mean + 2 so, from 25 to 50% with the 99th percentile, and from 47 to 64% with the 97.5% prediction interval. Conclusion We do not recommend age-referenced adjustments in upper limits for serum PSA concentration, but recommend that an upper limit of 4.0 ng/mL be used in all men 50-74 years of age.