Age-Specific Reference Ranges for Prostate-Specific Antigen as a Marker for Prostate Cancer

More than a decade ago, several investigators found serum PSA levels in cancer-free men to correlate directly with age and prostatic volume. This provided the basis for the establishment of age-specific reference ranges for PSA constituting an attempt to improve sensitivity and specificity of serum PSA as a marker for prostate cancer. Differing age-specific reference ranges for PSA were established in whites, African Americans, Asians, and Orientals. Moreover, since the introduction of different molecular forms of PSA with the inherent capability to differentiate between benign and malignant disease, age-specific reference ranges for free and complexed PSA have also been established. Subsequent studies sought to evaluate whether the standard 4.0 ng/ml cutoff should be replaced by age-adjusted cutoffs. Multiple trials involving various test modalities yielded inconclusive results. More recently, attempts were made to integrate principles of PSA density and PSA velocity into concepts of age-adjusted cutoffs for PSA envisioning more sensitive and specific PSA driven screening regimens. Hypothetical approaches involving age in association with prostatic growth or longitudinal data of PSA changes in individual men await further evaluation in prospective clinical trials. In conclusion, the usefulness of age-specific PSA ranges remains controversial because of concerns that the use of age-adjusted cutoffs for counselling men to undergo prostate biopsy runs the risk of missing a high proportion of clinically significant cancers in older men and augments the rate of unnecessary biopsies in younger men.