Prostate-specific antigen (PSA). What is it and why measure it?

Prostate-specific antigen (PSA) is a protein predominantly produced in the prostate by both normal and malignant cells. Blood levels of PSA are a useful indicator of prostatic pathology, to evaluate men at risk of prostate cancer, and for assessment after treatment.

What are the roles of PSA?
In normal healthy individuals, PSA is secreted into the seminal fluid in high concentrations to liquefy seminal gel by proteolytic cleavage of gel-forming proteins. This helps to increase sperm mobility. A small amount of PSA is also normally found in the blood as a result of leakage from the prostate gland (1).

What are normal blood PSA levels?
Healthy males generally have blood total PSA levels less than 4 ng/mL. Although most studies to establish this normal range have been conducted in predominantly white male populations; hence how applicable this value is to other racial or ethnic groups requires further investigation (2).

What do elevated blood PSA levels mean?
High levels of PSA in the blood can be indicative of prostate cancer, but may also occur due to benign (non-cancerous) conditions, including prostatitis (inflammation of the prostate), urinary tract infection, and benign prostatic hyperplasia (BPH, enlargement of the prostate) (3). More info about other causes of high PSA is available here. 

There are three major forms of PSA in the blood, two of which are detectable using current lab techniques – complexed PSA and free PSA (1). The differing levels of these two detectable forms are useful for distinguishing between individuals with BPH and prostate cancer, particularly in men with total PSA levels between 4.1 and 10 ng/mL. Although both abnormalities result in increased total blood PSA, the proportion of free PSA is much higher in individuals with BPH compared to prostate cancer patients (4).

What are the benefits of measuring blood PSA levels?
Prostate cancer is the most frequently diagnosed cancer and second leading cause of cancer deaths in men in the United States (5). Early diagnosis of small tumours that are confined to the prostate provides the best prognosis for recovery from prostate cancer. However, there are often no symptoms in the early stages of prostate cancer. Analyses of blood PSA levels are the most accurate and non-invasive way to detect prostate cancer, particularly in the early stages. These analyses are usually combined with, or followed up by, digital rectal examination (6).

References:
1. McCormack RT, et al. (1995). Molecular Forms of Prostate-Specific Antigen and the Human Kallikrein Gene Family: A New Era. Urology, 45, 729-744.
2. Prostate-Specific Antigen (PSA) Test. National Cancer Institute, NIH. (Updated Feb 2021)
3. Partin AW, Oesterling JE. (1994). The Clinical Usefulness of Prostate Specific Antigen: Update 1994. J Urol, 152, 1358-1368.
4. Ito K, et al. (2003). Free/total PSA ratio is a powerful predictor of future prostate cancer morbidity in men with initial PSA levels of 4.1 to 10.0 ng/mL. Urology. 61(4), 760-4.
5. Parker SL, et al. (1997). Cancer Statistics, 1997. CA Cancer J Clin, 47, 5-27.
6. Crawford ED, et al. (1996). Serum Prostate-Specific Antigen and Digital Rectum Examination for Early Detection of Prostate Cancer in a National Community-Based Program. Urology, 47, 863-869.