Prostate-Specific Antigen (PSA), Total and Free


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Subject: Prostate-Specific Antigen (PSA), Total and Free

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  • PSA is a glycoprotein that is expressed by both normal and neoplastic prostate tissue and is prostate tissue specific and not prostate cancer specific. PSA is consistently expressed in nearly all prostate cancers, although its level of expression on a per cell basis is lower than in normal prostate epithelium. The absolute value of serum PSA is useful for determining the extent of prostate cancer and assessing the response to prostate cancer treatment; its use as a screening method to detect prostate cancer is also common, although controversial.

  • PSA exists primarily as three forms in serum. One form of PSA is enveloped by the protease inhibitor, alpha-2 macroglobulin, and has been shown to lack immunoreactivity. A second form is complexed to another protease inhibitor, alpha-1 antichymotrypsin (ACT). The third form of PSA is not complexed to a protease inhibitor and is termed “free PSA.” The latter two forms are immunologically detectable in commercially available PSA assays and are referred to collectively as “total PSA.”

  • Free PSA values alone have not been shown to be effective in patient management and should not be used. Both total PSA and free PSA concentrations should be determined on the same serum specimen and used to calculate the percentage of free PSA. Percent free PSA values are then used for patient management.

TABLE 16–69
Normal Range


  • Monitoring patients with a history of prostate cancer as an early indicator of recurrence and response to treatment

  • Prostate cancer screening


Increased In*

  • Prostate diseases

    • Cancer

    • Prostatitis, five to seven times

    • Benign prostatic hyperplasia

    • Prostatic ischemia

    • Acute urinary retention five to seven times

  • Manipulations

    • Prostatic massage, ≤2 times

    • Cystoscopy: four times

    • Needle biopsy: >50 times for ≤1 month

    • Transurethral resection: >50 times

    • Digital rectal examination increases PSA significantly if initial value is >20 ng/mL and is not a confusing factor in falsely elevating PSA.

    • Radiation therapy

    • Indwelling catheter

    • Vigorous bicycle exercise: ≤2–3 times several days

  • Treadmill stress test: no change.

  • Drugs (e.g., testosterone).

  • Physiologic fluctuations: ≤30%.

  • PSA has no circadian rhythm, but 6–7% variation can occur between specimens collected on same day.

  • Ambulatory values are higher than sedentary values, which may decrease ≤50% (mean = 18%).

  • Ejaculation causes transient increase <1.0 ng/mL for 48 hours.

  • Analytic factors

    • Different assays yield different values

    • Antibody cross-reactivity

    • High titer heterophile antibodies

  • Other diseases/organs

    • Also found in small amounts in other cancers (sweat and salivary glands, breast, colon, lung, ovary) and in Skene glands of female urethra and in term placenta

    • Acute renal failure

    • Acute myocardial infarction

Decreased In

  • Ejaculation within 24–48 hours

  • Castration

  • Antiandrogen drugs (e.g., finasteride)

  • Radiation therapy

  • Prostatectomy

  • PSA falls 17% in 3 days after lying in hospital

  • Artifactual (e.g., improper specimen collection; very high PSA levels)

  • Finasteride (5-α-reductase inhibitor) reduces PSA by 50% after 6 months in men without cancer


  • PSA has been recommended by the American Cancer Society for use in conjunction with a DRE for the early detection of prostate cancer starting at age 50 years for men with at least a 10-year life expectancy. Men at high risk, such as those of African descent or with a family history of the disease, may begin testing at an earlier age.

  • PSA levels that are measured repeatedly over time may vary both because of imprecision in the analysis and biologic variability where the true PSA level in a given man is different on different measurements. This could potentially lead to an apparent rise in the PSA level, when no actual rise had occurred.

  • It is highly recommended that the same assay method be used for longitudinal monitoring.

  • A change in PSA of >30% in men with a PSA initially below 2.0 ng/mL was likely to indicate a true change beyond normal random variation.

  • The acceptable PSA levels are less clear after radiation therapy, where values may not reach undetectable concentrations. With a nadir of <0.5 ng/mL, relapse is not likely with 5 years of treatment. Biochemical recurrence has been defined by the ASTRO as three consecutive increases in PSA above the nadir.

  • The 5-α-reductase inhibitor drugs may affect PSA levels in some patients. Other drugs used to treat benign prostatic hyperplasia may also affect PSA levels. Drugs that decrease PSA levels include buserelin, finasteride, and flutamide. Care should be taken in interpreting results from patients taking these drugs.

  • Although screening for prostate cancer with PSA can reduce mortality due to prostate cancer, the absolute risk reduction is small. ACS recommends providing sufficient information regarding risks and benefits of screening and treatment to men to make informed shared decision. For those who decide to screen PSA with or without DRE for average-risk men beginning 50 years of age. Screening should not be offered to men whose life expectancy is <10 years. Men who have >2.5 ng/mL level should undergo annual testing.

  • AUA guidelines recommend screening against men younger than 40 years of age and does not recommend routine screening for average-risk men of 40–54 years of age, men older than 70 years, or men whose life expectancy of <10–15 years.

  • USPSTF recommend that men not to be screened for prostate cancer. They did advise that men requesting screening be supported in making an informed decision.