WHO First International Standards for Prostate-specific Antigen: The Beginning of the End for Assay Discrepancies?

Despite the success of prostate-specific antigen (PSA) as a tumor marker for the early detection and monitoring of disease in prostate cancer, both clinical and analytical limitations of PSA remain (1). Since the introduction of assays for total PSA in the mid-1980s, assay results have been found to differ among manufacturers (2)(3). Much has been learned in the last two decades about the biology of PSA and the molecular forms of PSA present in serum. Differences among assays still persist, however, even among assays from the same manufacturer that have the same antibodies but different assay formats. With the availability of the First International Standards from WHO, is this the beginning of the end for assay discrepancies? The lack of standardization of PSA was recognized early on as contributing to disparities among assays. Similar to some other tumor markers, a lack of defined antigens, differences in calibrator composition and specific molecular forms, and differences in calibrator assignments as well as the lack of a reference method are some of the issues hampering assay standardization. The lack of standardization of PSA prompted several organizations as well as individual researchers to convene meetings and conferences to address the issue. The Second Stanford Conference on International Standardization of Prostate-specific Antigen (4) was held in 1994. At this conference, the use of a standard, prepared at Stanford by Tom Stamey, consisting of 90% purified PSA-α1-antichymotrypsin (ACT) and 10% free PSA (90:10) on a molar basis was proposed with the rationale that …