[5] PSA is produced for the ejaculate, where it liquefies semen in the seminal coagulum and allows sperm to swim freely.

[10] In the United States, the Food and Drug Administration (FDA) has approved the PSA test for annual screening of prostate cancer in men of age 50 and older.

[medical citation needed] In the United Kingdom, the National Health Service (NHS) as of 2018[update] does not mandate, nor advise for PSA test, but allows patients to decide based on their doctor's advice.

[13] False-positive test results can cause confusion and anxiety in men, and can lead to unnecessary prostate biopsies, a procedure which causes risk of pain, infection, and hemorrhage.

[failed verification] Since the expected harms relative to risk of death are perceived by patients as minimal, men found to have prostate cancer usually (up to 90% of cases) elect to receive treatment.

D'Amico criteria for each risk category are:[17] Given the relative simplicity of the 1998 D'Amico criteria (above), other predictive models of risk stratification based on mathematical probability constructs exist or have been proposed to allow for better matching of treatment decisions with disease features.

[18] Studies are being conducted into the incorporation of multiparametric MRI imaging results into nomograms that rely on PSA, Gleason grade, and tumor stage.

[citation needed] Following radiation therapy of any type for prostate cancer, some PSA levels might be detected, even when the treatment ultimately proves to be successful.

This makes interpreting the relationship between PSA levels and recurrence/persistence of prostate cancer after radiation therapy more difficult.

A subsequent increase in PSA levels by 2.0 ng/mL[disputed – discuss] above the nadir is the currently accepted definition of prostate cancer recurrence after radiation therapy.

PSA was first identified by researchers attempting to find a substance in seminal fluid that would aid in the investigation of rape cases.

Because PSA is a biomarker that is expressed independently of spermatozoa, it remains useful in identifying semen from vasectomized and azoospermic males.

[23] PSA can also be found at low levels in other body fluids, such as urine and breast milk, thus setting a high minimum threshold of interpretation to rule out false positive results and conclusively state that semen is present.

[25] This level of antigen has been shown to be present in the peripheral blood of males with prostate cancer, and rarely in female urine samples and breast milk.

[24] PSA is produced in the epithelial cells of the prostate, and can be demonstrated in biopsy samples or other histological specimens using immunohistochemistry.

Prostate cancer cells generally have variable or weak staining for PSA, due to the disruption of their normal functioning.

In fertile couples, the final vaginal pH after coitus approaches the 6-7 levels, which coincides well with reduced zinc inhibition of PSA.

Li and Beling, in 1973, isolated a protein, E1, from human semen in an attempt to find a novel method to achieve fertility control.

However, prostate cancer can also be present in the complete absence of an elevated PSA level, in which case the test result would be a false negative.

However, the effect is clinically insignificant, since DRE causes the most substantial increases in patients with PSA levels already elevated over 4.0 ng/mL.

[66] However, both total and free PSA increase immediately after ejaculation, returning slowly to baseline levels within 24 hours.

Measuring the activity of the enzyme could add to the ratio of free-to-total PSA and further improve the diagnostic value of test.

[74] Tissue samples can be stained for the presence of PSA in order to determine the origin of malignant cells that have metastasized.