proPSA

proPSA refers to precursor forms of prostate-specific antigen (PSA), a serine protease produced by prostatic epithelial cells. PSA in blood exists in several forms, including total PSA (tPSA), free PSA (fPSA), and various PSA isoforms that retain the propeptide. The most studied proPSA isoform in cancer risk assessment is the truncated form known as [−2]proPSA (p2PSA). proPSA forms are measured with specialized immunoassays and are not typically used as a stand-alone diagnostic test; rather, they are considered within broader risk assessment tools.

A clinically notable application of proPSA is in the Prostate Health Index (phi), which combines [−2]proPSA, free PSA, and total PSA to improve detection of clinically significant prostate cancer. The phi score is calculated as ([−2]proPSA / free PSA) × sqrt(total PSA). In practice, higher levels of p2PSA and higher phi values are associated with a greater likelihood of prostate cancer and, often, with higher-grade tumors. The phi test aims to improve specificity and reduce unnecessary biopsies in men with elevated PSA or ambiguous results.

Interpretation and limitations: proPSA testing is intended to supplement, not replace, traditional PSA testing and clinical assessment. Results should be considered alongside patient age, race, family history, digital rectal exam findings, imaging, and other risk factors. The availability and recommended use of proPSA and phi vary by country and clinical guidelines, reflecting evolving evidence and assay designs.

History and regulatory status: Research on proPSA emerged in the early 2000s, with commercial assays for [−2]proPSA and phi introduced later. Regulatory approval and clinical adoption differ by region and over time.