Prostate-Specific Antigen

PSA is a kallikrein-related serine protease (also known as kallikrein-3 or KLK3) whose physiological function is to liquefy semen after ejaculation. Under normal conditions, very small amounts of PSA enter the bloodstream. When the prostate gland is affected by cancer, hyperplasia, inflammation, or physical manipulation, the barrier between prostate tissue and the circulatory system is disrupted, allowing larger quantities of PSA to reach the blood. A total serum PSA level above 4.0 ng/mL has traditionally been used as a referral threshold for prostate biopsy, though this cutoff has evolved significantly in modern clinical practice.

PSA exists in the blood in two primary forms: free PSA (unbound) and complexed PSA (bound to protease inhibitors such as alpha-1-antichymotrypsin). The ratio of free to total PSA provides additional diagnostic information — prostate cancer tends to produce more complexed PSA, so a lower free-to-total ratio may indicate higher cancer probability. Other PSA derivatives, including PSA density (adjusted for prostate volume), PSA velocity (rate of change over time), and the Prostate Health Index (phi), have been developed to improve the specificity of PSA-based evaluation.

PSA screening remains one of the most debated topics in preventive medicine. While PSA testing has contributed to the detection of early-stage prostate cancer, it also leads to overdiagnosis of clinically insignificant cancers, resulting in unnecessary biopsies and treatments. Current guidelines from organizations including the USPSTF recommend shared decision-making between patients and clinicians, with individualized assessment of the risks and benefits of PSA testing based on age, family history, and personal preferences.

Prevena Health is investigating whether continuous PSA monitoring may improve the clinical utility of PSA kinetics. PSA velocity and doubling time are recognized as potentially important parameters, but their calculation currently relies on infrequent blood draws spaced months or years apart, introducing significant measurement noise. Continuous surveillance through a wearable biosensor aims to provide a more precise and granular picture of PSA trajectories, potentially distinguishing clinically significant changes from normal biological fluctuation.

This approach may be particularly valuable for men on active surveillance for low-risk prostate cancer, where more frequent PSA data could support earlier identification of patients whose disease trajectory warrants intervention. Prevena is also exploring whether continuous PSA trend data, combined with other circulating biomarkers, may contribute to multi-analyte approaches that improve specificity for clinically significant prostate cancer.