Prostate specific antigen or PSA is one of the markers of prostate cancer. PSA is normally produced by the prostate gland and mixes with sperm to form semen. PSA helps make semen fluid, allowing sperm to swim freely. Small amounts of PSA are also detectable in the blood.

Normal levels

A blood PSA level of below 4 ng/mL is considered normal, although there is debate about the optimal cut-off value for a normal PSA level, with some researchers favouring a value of 2.5 ng/mL.

When is PSA raised?

PSA is also secreted in large amounts by prostate cancer cells. As the prostate cancer progresses, the blood levels of PSA begin to rise. In addition, the risk of prostate cancer developing rises with increasing PSA levels. Men who have borderline raised PSA of between 4 and 10 ng/mL have a 25% risk of developing prostate cancer and this risk is raised to 50% if the PSA rises above 10 ng/mL.

Why is depending entirely on PSA a problem?

PSA level analysis is not a definitive test for prostate cancer. Many men may develop prostate cancer, despite having a PSA level below 4 ng/mL, which happens in around 15% of all prostate cancer cases. While men who have a PSA level below the cut-off that is considered normal may still have prostate cancer, men with high PSA levels may not necessarily have prostate cancer.

Furthermore, PSA levels fluctuate for various reasons and may be raised in cases of prostatisis, urinary tract infection or benign enlargement of the prostate, for example. A PSA level may even be increased after a man has engaged in physical activity or sex. Other factors that influence PSA level include advancing age, urological procedures, the use of testosterone-enhancing drugs, obesity and the use of certain medications such as aspirin or cholesterol-lowering agents.

Another factor that reduces the reliability of PSA is the fact that the cut-off for normal levels has mainly been based during studies of white males and are not necessarily applicable to other racial groups.

What is false positive and false negative?

A false positive result for cancer is a test result that is positive for cancer when in fact no cancer is present. A false negative result is a test result that gives a negative for cancer when in fact cancer is present.

In a man with no symptoms of prostate cancer, if routine PSA screening shows elevated levels of PSA, another PSA test is recommended to confirm the original finding. If that test also indicates cancer, a digital rectal examination (DRE) is performed. If an abnormality such as a hardening or lump is detected on DRE, further tests such as imaging studies are recommended and a prostate biopsy is taken to confirm the diagnosis.

The disadvantage of PSA testing is lack of specificity for prostate cancer. A false positive test may cause a man and his family a great deal of anxiety unnecessarily and may also lead to additional medical procedures such as a prostate biopsy which can cause complications such as rectal bleeding or infection. A false-negative test result, on the other hand, may give a man and his family the impression that he is cancer-free when in fact he does have a cancer that will require treatment.