2proPSA

2proPSA, also known as [-2]proPSA or p2PSA, is a proteolytically truncated isoform of prostate-specific antigen (PSA). Like PSA, it is produced by prostate tissue and circulates in the blood, but it differs in its N-terminal structure. 2proPSA is measured as part of the Prostate Health Index (PHI), a multicomponent test used to assess prostate cancer risk, particularly when total PSA falls within the borderline range.

Measurement and interpretation: 2proPSA is detected in serum using immunoassays. The PHI combines 2proPSA with free PSA (fPSA) and total PSA (tPSA) to produce a single score. A commonly cited formulation is PHI = (2proPSA / fPSA) × sqrt(tPSA). Higher PHI values are associated with a greater likelihood of clinically significant prostate cancer, assisting decisions about whether to perform a biopsy.

Clinical utility: The use of 2proPSA within PHI has been shown to improve specificity for detecting prostate cancer compared with total PSA alone, potentially reducing unnecessary biopsies while maintaining sensitivity for significant cancers. It is often considered for men with elevated PSA values or indeterminate results, and can be used in conjunction with imaging and other risk factors.

Limitations: 2proPSA and PHI are not standalone diagnostic tests. Results can be influenced by factors such as age, race, prostatitis, infections, and prostate volume. Availability, assay standardization, and integration into clinical workflows vary by laboratory and region.

History: 2proPSA emerged from research on PSA isoforms in the early 2000s and has since become a component of risk assessment panels used in many clinical settings.