PSA Screening

Prostate-Specific Antigen (PSA) Screening


PSA is a serine protease member of the human kallikrein family. It is produced in both normal and cancerous prostate tissue and secreted into seminal fluid. Its physiologic function is to liquefy semen from its gel form. Normal prostate architecture keeps PSA confined to the gland, and only a small portion is leaked into the circulation. PSA circulates in free and complexed forms. Free forms represent 5%-35% of total PSA. Complexed forms (65%-95%) are bound to protease inhibitors. Binding inactive protease and PSA in the blood has no catalytic activity.

Serum PSA elevations occur as a result of disruptions in the prostate architecture that allow PSA to enter the circulation. This can occur in disease settings (PC [Prostate Cancer], BPH [Benign Prostatic Hyperplasia], or prostatitis [inflammation of the prostate]) or after prostate manipulation (massage, biopsy, or transurethral resection). Increased levels in PC patients cannot be explained by increased synthesis. In fact, PSA expression is slightly decreased in cancer tissue. A prostate-specific antigen (PSA) test measures the amount of prostate-specific antigen in the blood.

Why It Is Done

The prostate-specific antigen (PSA) test is done to:

Before the Test

Before you have a prostate-specific antigen (PSA), tell your doctor if you have had a:

Do not ejaculate for 48 hours before your PSA blood test, either during sex or masturbation. Do not exercise heavily 48 hours before the test.

A raised PSA level may mean you have prostate cancer but about two out of three men with a raised PSA level will not have prostate cancer.

Other conditions may also cause a raised PSA level, including:

How PSA Test Is Done?

The health professional taking a sample of your blood will:

How is PSA test measured?

PSA is measured by a simple blood test that does not require fasting or special preparation. Since the amount of PSA in the blood is very low, detection of it requires a very sensitive type of technology (monoclonal antibody technique). The PSA protein can exist in the blood by itself (known as free PSA) or be bound with other substances (known as bound or complexed PSA). PSA is mostly bound to three substances: alpha-2-macroglobulin, alpha 1-antichymotrypsin (ACT), and albumin. Total PSA is the sum of the free and the bound forms. The total PSA is what is measured with the standard PSA test. More recently, a precursor of PSA, proenzyme PSA ([-2] proenzyme PSA), has been identified, which may be helpful in determining prostate cancer risk in men with a PSA under 10 and a normal digital rectal examination. The prostate health index (PHI) is a new approved test that measures the total PSA, free PSA, and [-2] proenzyme PSA.

The normal range changes as you get older.

PSA Cut-off Values

Age (years)

PSA Cut-off

40-49 2.0 nanogram/mL or higher
50-59 3.0 nanogram/mL or higher
60-69 4.0 nanogram/mL or higher
70 or older 5.0 nanogram/mL or higher
There are no age-specific reference limits for men older than 80 years of age.

The higher the level of prostate specific antigen (PSA), the more likely it is to be a sign of cancer.

Variations of the PSA test

Your doctor might use other ways of interpreting PSA results before deciding whether to order a biopsy to test for cancerous tissue. These other methods are intended to improve the accuracy of the PSA test as a screening tool.

Researchers continue to investigate variations of the PSA test to determine whether they provide a measurable benefit.

Variations of the PSA test include:

PSA Density?

Although PSA expression is higher in men with BPH, prostate cancer tissue releases more PSA into circulation. Volume-based prostate parameters have been evaluated to better interpret PSA levels in men with large prostates.

Patients with BPH have transition zone (TZ) enlargement; most prostate cancers arise in the peripheral zone (PZ). Adjusting PSA to account for TZ volume has been evaluated as a method of distinguishing PC from BPH. Thresholds of 0.23 and 0.38 ng/mL/cm3 were proposed for TZ volumes above 20 cc and below 20 cc, respectively.

PSA density (PSAD) is the serum PSA level divided by prostate volume as assessed by transrectal ultrasound. A direct relationship between PSAD and the risk of cancer is also reported. PSAD cutpoints between 0.10 and 0.18 ng/mL/cc were proposed as the levels that should prompt prostate biopsy. However, using 0.15 ng/mL/cc as the cutoff, half of the cancers detected in men with PSA between 4.0 and 10.0 ng/mL would have been missed. Lower cutpoints appear to maximize sensitivity and specificity. PSAD has also been associated with tumor aggressiveness and treatment outcomes.

PSAD is not widely used, as it is an uncomfortable, invasive method requiring skillful performance of transrectal ultra-sonography in which accuracy is influenced by the shape of the prostate. Furthermore, it is more time consuming and expensive than a simple blood test.

What are the Risks associated with the PSA test?

There is very little chance of a problem from having a blood sample taken from a vein.

What can lower the PSA test result?

Medications commonly taken to treat benign enlargement of the prostate (BPH) such as finasteride (Proscar), dutasteride(Avodart), and a combination of dutasteride and tamsulosin (Jalyn) can decrease the PSA by about 50% within six to 12 months of starting their use. Another medication used to treat fungal infections, ketoconazole, can also lower PSA levels. Lastly, herbal supplements such as saw palmetto and those containing phytoestrogens, which are plant-derived chemicals with estrogen-like effects, can also lower the PSA level. It is important to tell your health care provider all the medications, both prescription and nonprescription, as well as any herbal preparations or health supplements that you are taking.

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