Age-specific reference ranges for serum prostate-specific antigen.

Since PSA was discovered nearly 20 years ago, significant progress has been made in improving the clinical utility of this glycoprotein as a tumor marker. Factors contributing to the initial limitations in sensitivity and specificity of PSA as a diagnostic tool for early cancer now are understood better. As a result, PSA now is being used [table: see text] widely for the diagnosis of early, curable prostate cancer. PSA, however, because of the inability to differentiate benign processes from malignancy, fails to perform at the ideal tumor-marker level. Nevertheless, in 1997, it remains the best tumor marker in all cancer biology. The research that has been conducted by several independent investigators, showing the correlation between PSA, prostate volume, and patient age, was a vital step in the process of improving the clinical and diagnostic utility of PSA. From this, Oesterling, Dalkin, DeAntoni and others have recommended similar age-specific reference ranges for serum PSA. Subsequent investigations have supported the initial theories that the use of age-specific reference ranges would improve the sensitivity of PSA in younger men, leading to the diagnosis of additional early, organ-confined prostate cancer. The issue of improved specificity in older men has been somewhat less straightforward in that decreasing negative biopsies also result in undetected prostate cancers. The real question involves determining what percent of these undetected prostate cancers are clinically significant to the older patient. Of additional significance is the determination of differing age-specific reference ranges in whites, Asians, and African-Americans (Table 1). In 1997, it is important to know not only the age of the patient but also the race of the patient to interpret the serum PSA concentration. The clinical meaning of a given serum PSA value differs from one race to the next. The recent discovery of the different molecular forms of PSA and their potential ability to improve the diagnostic specificity of PSA is another significant step. Accordingly, the information about the relationship of age to the specific molecular forms and their ratios is a necessity. As urologists continue the quest for the ideal tumor marker for prostate cancer, utilizing age-specific reference ranges will continue to improve the clinical utility of the PSA test.