Prostate specific antigen (PSA), total

PSA is a single chain chymotrypsin-like serine protease of approximately 30 kDa. It is produced by the epithelial cells lining the acini and ducts of the prostate gland, and plays a role in the liquefaction of seminal fluid. Low levels of PSA are found in the blood as a result of leakage from the prostate gland. Increasing levels of serum PSA are associated with prostatic pathology, including prostatitis, benign prostatic hyperplasia (BPH) and cancer of the prostate. Urinary retention, transurethral resection of the prostate (TURP), prostate biopsy, prostate massage and ejaculation may also give rise to increases is serum PSA levels. In the sera PSA is mostly bound to either α-2 macroglobulin (AMG) or α-1 antichymotrypsin (ACT). The total PSA test measures free PSA and that bound to ACT with approximate equimolarity. PSA bound to AMG is not detected by the total PSA test. The proportion of protein-bound PSA increases in malignancy compared with that observed in BPH or prostatitis. Hence, separate measurement of free PSA and calculation of the ratio (the %fPSA test) is helpful in distinguishing men with prostate cancer from men with BPH (see percentage free PSA test for more details). Although PSA levels increase in age and there have been arguments to revise the current cut-off of ≥4.0 µg/L, no overall clinical benefit for raising or lowering has been clearly demonstrated. Repeat testing to ascertain the rate of increase in total PSA is a helpful approach for increasing specificity of total PSA for distinguishing prostate cancer.

Diagnosis: due to the wide inter- and intra-individual variation in serum PSA levels in healthy men and overlap with PSA levels observed in disease, total PSA measurement should be used in combination with digital rectal examination (DRE) in men suspected of having prostate cancer. Percentage free PSA measurement and repeat testing can also be used to enhance specificity. Prognosis and staging: total PSA levels correlate stage of disease and can be used for determining prognosis
Treatment monitoring: PSA is useful in monitoring response to treatment.
Surveillance: PSA is used for detection of early recurrence following prostatectomy.

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