p2PSA

p2PSA, or proenzyme prostate‑specific antigen 2, is a biochemical form of the PSA molecule that remains in its inactive proenzyme state. It is produced by prostate epithelial cells and is released into circulation in both malignant and benign conditions, but its relative concentration differs between cancer and benign disease. Clinically, p2PSA is most commonly used as part of the prostate health index (PHI), a composite score that combines total PSA, free PSA, and p2PSA values to improve risk stratification for prostate cancer. The PHI has been shown in multiple prospective studies to provide higher sensitivity and specificity for clinically significant prostate cancer compared with total PSA alone, particularly in men with intermediate PSA levels (4‑10 ng/mL).

Analytical measurement of p2PSA is performed by immunoassay kits that employ monoclonal antibodies specific to the proenzyme form. Results are expressed in nanograms per milliliter and are usually reported alongside total and free PSA values for PHI calculation. Regulators such as the U.S. Food and Drug Administration have cleared several commercial PHI assays for diagnostic use.

Guideline bodies, including the American Urological Association, suggest that PHI can be considered for decision making regarding repeat biopsies or active surveillance, especially when PSA trends are ambiguous. However, PHI is not a standalone diagnostic tool and is typically used in conjunction with clinical examination, imaging, and patient preferences.