Standardization of Prostate-Specific Antigen (PSA) Assays: Can Interchangeability of PSA Measurements Be Improved?

The landscape of prostate cancer has changed since the appearance of the first prostate-specific antigen (PSA) assay. PSA testing has gained rapid recognition since M. Kuriyama et al. (1) of Roswell Park first reported clinical studies using an enzyme immunoassay with anti-PSA rabbit antibody. Mikolajczyk and coworkers (2)(3) reported the presence of several free PSA isoforms and the potential application of free PSA isoforms as serum markers. Today, more than 30 types of total PSA assay reagent sets and ∼10 types of free PSA and PSA–α1-antichymotrypsin (ACT) assays, based on various principles, are available. Key elements in PSA measurement are interchangeability of assays and stability of serum samples before tests (4)(5). Efforts to standardize PSA assays were initiated in 1992 at the First Stanford Conference, organized by T. Stamey. At the Second Stanford Conference on International Standardization of Prostate-Specific Antigen (1994), Stamey et al. (6) proposed a primary calibrator consisting of 90% purified PSA-ACT and 10% free PSA (90:10) on a molar basis. Subsequently, the Clinical and Laboratory Standards Institute (CLSI; formerly NCCLS) issued a document (7) recommending a set of 3 distinct materials containing 100% free PSA, 100% PSA-ACT, and 90% PSA-ACT:10% free PSA. This document led to further activity in the harmonization of PSA assays. In 1999, Robert M. Nakamura, a member of the International Consultation Committee on Prostate Cancer, made recommendations, with his colleagues (8), on standardization and quality assessment of …