Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a glycoprotein enzyme encoded in humans by the KLK3 gene. PSA is a member of the kallikrein-related peptidase family and is secreted by the epithelial cells of the prostate gland in men and the paraurethral glands in women. PSA is produced for the ejaculate, where it liquefies semen in the seminal coagulum and allows sperm to swim freely. It is also believed to be instrumental in dissolving cervical mucus, allowing the entry of sperm into the uterus. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer or other prostate disorders. PSA is not uniquely an indicator of prostate cancer, but may also detect prostatitis or benign prostatic hyperplasia.
Medical diagnostic uses
Prostate cancer
Screening
Clinical practice guidelines for prostate cancer screening vary and are controversial, in part due to uncertainty as to whether the benefits of screening ultimately outweigh the risks of overdiagnosis and overtreatment. 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. The patient is required to be informed of the risks and benefits of PSA testing prior to performing the test. In the United Kingdom, the National Health Service (NHS) as of July 2025 does not mandate, nor advise routine PSA testing, but allows patients over 50 to request a test based on their doctor's advice, in an "informed choice programme called prostate cancer risk management for healthy men". The charity Prostate Cancer UK, however, recommend men discuss PSA testing from the age of 45. PSA levels between 4 and 10 ng/mL (nanograms per millilitre) are considered to be suspicious, and consideration should be given to confirming the abnormal PSA with a repeat test. If indicated, prostate biopsy is performed to obtain a tissue sample for histopathological analysis. While PSA testing may help 1 in 1,000 avoid death due to prostate cancer, 4 to 5 in 1,000 would die from prostate cancer after 10 years even with screening. This means that PSA screening may reduce mortality from prostate cancer by up to 25%. Expected harms include anxiety for 100–120 receiving false positives, biopsy pain, and other complications from biopsy for false positive tests. Use of PSA screening tests is also controversial due to questionable test accuracy. The screening can present abnormal results even when a man does not have cancer (known as a false-positive result), or normal results even when a man does have cancer (known as a false-negative result). 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. False-negative results can give men a false sense of security, though they may actually have cancer. Of those found to have prostate cancer, overtreatment is common because most cases of prostate cancer are not expected to cause any symptoms due to low rate of growth of the prostate tumor. Therefore, many will experience the side effects of treatment, such as for every 1000 men screened, 29 will experience erectile dysfunction, 18 will develop urinary incontinence, two will have serious cardiovascular events, one will develop pulmonary embolus or deep venous thrombosis, and one perioperative death. 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.
Risk stratification and staging Men with prostate cancer may be characterized as low, intermediate, or high risk for having/developing metastatic disease or dying of prostate cancer. PSA level is one of three variables on which the risk stratification is based; the others are the grade of prostate cancer (Gleason grading system) and the stage of cancer based on physical examination and imaging studies. D'Amico criteria for each risk category are:
Low risk: PSA < 10, Gleason score ≤ 6, AND clinical stage ≤ T2a Intermediate risk: PSA 10–20, Gleason score 7, OR clinical stage T2b/c High risk: PSA > 20, Gleason score ≥ 8, OR clinical stage ≥ T3 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. Studies are being conducted into the incorporation of multiparametric MRI imaging results into nomograms that rely on PSA, Gleason grade, and tumor stage.
Post-treatment monitoring PSA levels are monitored periodically (e.g., every 6–36 months) after treatment for prostate cancer – more frequently in patients with high-risk disease, less frequently in patients with lower-risk disease. If surgical therapy (i.e., radical prostatectomy) is successful at removing all prostate tissue (and prostate cancer), PSA becomes undetectable within a few weeks. A subsequent rise in PSA level above 0.2 ng/mL L is generally regarded as evidence of recurrent prostate cancer after a radical prostatectomy; less commonly, it may simply indicate residual benign prostate tissue. 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. PSA levels may continue to decrease for several years after radiation therapy. The lowest level is referred to as the PSA nadir. A subsequent increase in PSA levels by 2.0 ng/mL above the nadir is the currently accepted definition of prostate cancer recurrence after radiation therapy. Recurrent prostate cancer detected by a rise in PSA levels after curative treatment is referred to as a "biochemical recurrence". The likelihood of developing recurrent prostate cancer after curative treatment is related to the pre-operative variables described in the preceding section (PSA level and grade/stage of cancer). Low-risk cancers are the least likely to recur, but they are also the least likely to have required treatment in the first place.
… excerpt ends here. Continue reading the full article.
