Prostate specific antigen (PSA) is currently used as a tumor marker for prostate cancer.
PSA is a 33-kilodalton glycoprotein produced in prostate epithelial cells. Its normal physiologic role is as a liquefying agent for seminal fluid; only a tiny amount leaks into the blood, so its normal serum level is usually very low.
Prostate specific antigen can exist in the serum in two forms:
bound/complexed (to serum protein): elevated levels are associated with prostate cancer
free PSA (fPSA): elevated levels are associated with benign prostatic hyperplasia (BPH)
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PSA levels
A threshold value of >3.0-4.0 ng/mL has long been used to determine an elevated or high PSA level; however, PSA is known to increase with age and, currently (c.2023), interpretation using an age-specific cut-off is recommended by the American Urological Association (considered elevated above this level) 8:
40-49 years: >2.5 ng/mL
50-59 years: >3.5 ng/mL
60-69 years: >4.5 ng/mL
70-79 years: >6.5 ng/mL
Elevated PSA levels are strongly associated with prostate cancer and is the first-line screening test for prostate cancer 8,9. However, it is commonly elevated in many non-malignant conditions 8,9:
manipulation (e.g. digital rectal exam, transrectal ultrasound)
recent ejaculation
A single absolute PSA level may also be misleading if there is a trend in the data upward or downward over time (can be calculated as PSA velocity). In patients with a newly increased PSA level, ~30% (range 25-40%) will have a level in the normal range on re-testing, and a repeat PSA (typically a few week to months later) is recommended prior to further evaluation 8,9.
Low or normal PSA levels do not confer the absence of disease or risk as prostate cancer can still rarely occur in patients with a low/normal PSA 9, and a PSA >1 ng/mL (at 40 years) or >2 ng/ML (at 60 years) confers an increased risk of subsequent prostate cancer metastases and death 9.
Post treatment
An upward trend in a patient's PSA value is usually concerning after a prostatectomy, raising suspicion for recurrent/metastatic disease ref.
Long term (> 6-12 months) treatment with 5α-reductase inhibitors (e.g. finasteride, dutasteride) tends to reduce the PSA level by about 50% 6.
PSA in women
Prostate specific antigen was at one time thought to be only secreted from the prostate, but it is now clear that it is also secreted by cells in women, in particular the breast. The normal serum PSA level in females is approximately 1,000 times less than in men 4,5.
PSA is synthesized by both healthy and pathological breast tissue, and studies suggest that an elevated serum PSA, may point towards a favorable prognosis in breast cancer and be useful in monitoring treatment response 4,5.
History and etymology
American pathology professor Richard J. Ablin discovered prostate specific antigen in 1970 7.
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