Test ID: PSAFT    
Prostate-Specific Antigen (PSA), Total and Free, Serum

Assessing the risk of prostate cancer in patients with borderline or moderately increased total PSA (4.0-10.0 ng/mL)

Determining which patients should have follow-up prostate biopsy

Prostate-specific antigen (PSA) is a glycoprotein that is produced by the prostate gland, the lining of the urethra, and the bulbourethral gland. Normally, very little PSA is secreted in the blood. Increases in glandular size and tissue damage caused by benign prostatic hypertrophy, prostatitis, or prostate cancer may increase circulating PSA levels.

PSA exists in serum in multiple forms: complexed to alpha-1-anti-chymotrypsin (PSA-ACT complex), unbound (free PSA), and enveloped by alpha-2-macroglobulin (not detected by immunoassays).

Higher total PSA levels and lower percentages of free PSA are associated with higher risks of prostate cancer.

Most prostate cancers are slow growing, so the utility of prostate cancer screening is marginal in most men with a life expectancy of less than 10 years.

When total prostate-specific antigen (PSA) concentration is below 2.0 ng/mL, the probability of prostate cancer in asymptomatic men is low, further testing and free PSA may provide little additional information. When total PSA concentration is above 10.0 ng/mL, the probability of cancer is high and prostate biopsy is generally recommended.

The total PSA range of 4.0 to 10.0 ng/mL has been described as a diagnostic "gray zone," in which the free PSA:total PSA ratio helps to determine the relative risk of prostate cancer (see table). Therefore, some urologists recommend using the free PSA:total ratio to help select which men should undergo biopsy. However, even a negative result of prostate biopsy does not rule-out prostate cancer. Up to 20% of men with negative biopsy results have subsequently been found to have cancer.

Based on free PSA:total PSA ratio: the percent probability of finding prostate cancer on a needle biopsy by age in years:

Normal results do not eliminate the possibility of prostate cancer.

Values obtained with different assay methods or kits may be different and cannot be used interchangeably.

Tumor markers are not specific for malignancy. Test results cannot be interpreted as absolute evidence for the presence or absence of malignant disease.

Specimens collected from patients undergoing prostate manipulation, especially needle biopsy and transurethral resection, may show erroneously high prostate-specific antigen (PSA) results. Care should be taken that specimens are obtained before these procedures are performed.

Prostate cancer patients receiving treatment with antiandrogens and luteinizing hormone-releasing factor agonists may exhibit markedly decreased levels of PSA. Also, men treated for benign prostatic hyperplasia with inhibitors of 5-alpha-reductase (finasteride) may demonstrate a significant reduction in PSA levels compared to values before treatment. Care should be taken in interpreting values for these individuals.

In rare cases, interference due to extremely high titers of antibodies to ruthenium or streptavidin can occur.

Serum biotin concentrations up to 1200 ng/mL do not interfere with this assay. Extremely high concentrations of biotin in patient serum due to heavy administration or supplementation of biotin may falsely decrease the results

1. Catalona WJ, Smith DS, Wolfert RL, et al: Evaluation of percentage of free serum prostate-specific antigen to improve specificity of prostate cancer screening. JAMA. 1995:274(15);214-1220

2. Oesterling JE, Jacobsen SJ, Klee GG, et al: Free, complexed and total serum prostate specific antigen: the establishment of appropriate reference ranges for their concentrations and ratios. J Urol. 1995;154:1090-1095

3. Duffy MJ. Biomarkers for prostate cancer: prostate-specific antigen and beyond. Clin Chem Lab Med. 2020 Feb 25;58(3):326-339

4. Catalona WJ: Prostate cancer screening. Med Clin North Am. 2018 Mar;102(2):199-214