PSA has two related meanings. Technically, it stands for Prostate-Specific Antigen, yet the term is also used as shorthand for the prostate cancer screening test that uses PSA. The goal of a PSA test is to look for warning signs that prostate cancer may be more likely to occur. It does this by measuring the amount of PSA in the blood.

• Prostate-specific antigen (PSA) is a protein produced by the cells of the prostate gland. The PSA test measures the level of PSA in the blood (see Question 1).
• The U.S. Food and Drug Administration (FDA) has approved the use of the PSA test along with a digital rectal exam to help detect prostate cancer in men age 50 and older. The FDA has also approved the PSA test to monitor patients with a history of prostate cancer to see if the cancer has come back (recurred) (see Question 2).
• Doctors recommendations for screening vary (see Question 3).
• The higher a mans PSA level, the more likely it is that cancer is present, but there are many other possible reasons for an elevated PSA level (see Questions 4 and 5).
• The PSA screening test has limitations and is still controversial (see Questions 6 and 7).

Prostate-specific antigen (PSA) is a protein produced by the cells of the prostate gland. The PSA test measures the level of PSA in the blood. The doctor takes a blood sample, and the amount of PSA is measured in a laboratory. Because PSA is produced by the body and can be used to detect disease, it is sometimes called a biological marker or tumor marker.

It is normal for men to have low levels of PSA in their blood; however, prostate cancer or benign (not cancerous) conditions can increase PSA levels. As men age, both benign prostate conditions and prostate cancer become more frequent. The most common benign prostate conditions are prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (BPH) (enlargement of the prostate). There is no evidence that prostatitis or BPH cause cancer, but it is possible for a man to have one or both of these conditions and to develop prostate cancer as well.

PSA levels alone do not give doctors enough information to distinguish between benign prostate conditions and cancer. However, the doctor will take the result of the PSA test into account when deciding whether to check further for signs of prostate cancer.

The U.S. Food and Drug Administration (FDA) has approved the PSA test along with a digital rectal exam (DRE) to help detect prostate cancer in men age 50 and older. During a DRE, a doctor inserts a gloved finger into the rectum and feels the prostate gland through the rectal wall to check for bumps or abnormal areas. Doctors often use the PSA test and DRE as prostate cancer screening tests; together, these tests can help doctors detect prostate cancer in men who have no symptoms of the disease.

The FDA has also approved the PSA test to monitor patients with a history of prostate cancer to see if the cancer has come back (recurred). An elevated PSA level in a patient with a history of prostate cancer does not always mean the cancer has come back. A man should discuss an elevated PSA level with his doctor. The doctor may recommend repeating the PSA test or performing other tests to check for evidence of recurrence.

It is important to note that a man who is receiving hormone therapy for prostate cancer may have a low PSA reading during, or immediately after, treatment. The low level may not be a true measure of PSA activity in the mans body. Men receiving hormone therapy should talk with their doctor, who may advise them to wait a few months after hormone treatment before having a PSA test.

Doctors recommendations for screening vary. Some encourage yearly screening for men over age 50, and some advise men who are at a higher risk for prostate cancer to begin screening at age 40 or 45. Others caution against routine screening, while still others counsel men about the risks and benefits on an individual basis and encourage men to make personal decisions about screening. Currently, Medicare provides coverage for an annual PSA test for all men age 50 and older.

Several risk factors increase a mans chances of developing prostate cancer. These factors may be taken into consideration when a doctor recommends screening. Age is the most common risk factor, with nearly 70 percent of prostate cancer cases occurring in men age 65 and older [1]. Other risk factors for prostate cancer include family history, race, and possibly diet. Men who have a father or brother with prostate cancer have a greater chance of developing prostate cancer. African American men have the highest rate of prostate cancer, while Asian and Native American men have the lowest rates. In addition, there is some evidence that a diet higher in fat, especially animal fat, may increase the risk of prostate cancer.

PSA test results report the level of PSA detected in the blood. The test results are usually reported as nanograms of PSA per milliliter (ng/ml) of blood. In the past, most doctors considered PSA values below 4.0 ng/ml as normal. However, recent research found prostate cancer in men with PSA levels below 4.0 ng/ml [2]. Many doctors are now using the following ranges, with some variation:

• 0 to 2.5 ng/ml is low
• 2.6 to 10 ng/ml is slightly to moderately elevated
• 10 to 19.9 ng/ml is moderately elevated
• 20 ng/ml or more is significantly elevated

While there is no specific normal or abnormal PSA level, the higher a mans PSA level, the more likely it is that cancer is present. However, because various factors can cause PSA levels to fluctuate, one abnormal PSA test does not necessarily indicate a need for other diagnostic tests. When PSA levels continue to rise over time, other tests may be needed.

A man should discuss elevated PSA test results with his doctor. There are many possible reasons for an elevated PSA level, including prostate cancer, benign prostate enlargement, inflammation, infection, age, and race.

If no other symptoms suggest cancer, the doctor may recommend repeating DRE and PSA tests regularly to watch for any changes. If a mans PSA levels have been increasing or if a suspicious lump is detected during the DRE, the doctor may recommend other tests to determine if there is cancer or another problem in the prostate. A urine test may be used to detect a urinary tract infection or blood in the urine. The doctor may recommend imaging tests, such as ultrasound (a test in which high-frequency sound waves are used to obtain images of the kidneys and bladder), x-rays, or cystoscopy (a procedure in which a doctor looks into the urethra and bladder through a thin, lighted tube). Medicine or surgery may be recommended if the problem is BPH or an infection.

If cancer is suspected, a biopsy is needed to determine if cancer is present in the prostate. During a biopsy, samples of prostate tissue are removed, usually with a needle, and viewed under a microscope. The doctor may use ultrasound to view the prostate during the biopsy, but ultrasound cannot be used alone to tell if cancer is present.

• Detection does not always mean saving lives: Even though the PSA test can detect small tumors, finding a small tumor does not necessarily reduce a mans chance of dying from prostate cancer. PSA testing may identify very slow-growing tumors that are unlikely to threaten a mans life. Also, PSA testing may not help a man with a fast-growing or aggressive cancer that has already spread to other parts of his body before being detected.
• False positive tests: False positive test results (also called false positives) occur when the PSA level is elevated but no cancer is actually present. False positives may lead to additional medical procedures that have potential risks and significant financial costs and can create anxiety for the patient and his family. Most men with an elevated PSA test turn out not to have cancer; only 25 to 30 percent of men who have a biopsy due to elevated PSA levels actually have prostate cancer [3].
• False negative tests: False negative test results (also called false negatives) occur when the PSA level is in the normal range even though prostate cancer is actually present. Most prostate cancers are slow-growing and may exist for decades before they are large enough to cause symptoms. Subsequent PSA tests may indicate a problem before the disease progresses significantly.

Using the PSA test to screen men for prostate cancer is controversial because it is not yet known if this test actually saves lives. Moreover, it is not clear if the benefits of PSA screening outweigh the risks of follow-up diagnostic tests and cancer treatments. For example, the PSA test may detect small cancers that would never become life threatening. This situation, called overdiagnosis, puts men at risk for complications from unnecessary treatment such as surgery or radiation.

The procedure used to diagnose prostate cancer (prostate biopsy) may cause side effects, including bleeding and infection. Prostate cancer treatment may cause incontinence (inability to control urine flow) and erectile dysfunction (erections inadequate for intercourse). For these reasons, it is important that the benefits and risks of diagnostic procedures and treatment be taken into account when considering whether to undertake prostate cancer screening.

The benefits of screening for prostate cancer are still being studied. The National Cancer Institute (NCI) is currently conducting the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, or PLCO trial, to determine if certain screening tests reduce the number of deaths from these cancers. The DRE and PSA are being studied to determine whether yearly screening to detect prostate cancer will decrease a mans chance of dying from prostate cancer.

Scientists also are researching ways to distinguish between cancerous and benign conditions, and between slow-growing cancers and fast-growing, potentially lethal cancers. Some of the methods being studied are:

• PSA velocity: PSA velocity is based on changes in PSA levels over time. A sharp rise in the PSA level raises the suspicion of cancer.
• Age-adjusted PSA: Age is an important factor in increasing PSA levels. For this reason, some doctors use age-adjusted PSA levels to determine when diagnostic tests are needed. When age-adjusted PSA levels are used, a different PSA level is defined as normal for each 10-year age group.
• PSA density: PSA density considers the relationship of the PSA level to the size of the prostate. In other words, an elevated PSA might not arouse suspicion if a man has a very enlarged prostate.
• Free versus attached PSA: PSA circulates in the blood in two forms: free or attached to a protein molecule. With benign prostate conditions, there is more free PSA, while cancer produces more of the attached form.
• Alteration of PSA cutoff level: Some researchers have suggested lowering the cutoff levels that determine if a PSA measurement is normal or elevated. Researchers hope that using these lower levels will increase the chance of detecting prostate cancer; however, this may also increase false positive test results, leading to unnecessary medical procedures.
• Protein patterns: Scientists are also studying a test that can rapidly analyze the patterns of various proteins in the blood. Researchers hope that this technique can determine if a biopsy is necessary when a person has a slightly elevated PSA level or an abnormal DRE.

For additional information about prostate cancer, contact the NCIs Cancer Information Service (see below).

1. Ries LAG, Eisner MP, Kosary CL, et al. (eds). SEER Cancer Statistics Review, 19752001, National Cancer Institute. Bethesda, MD, 2004 (http://seer.cancer.gov/csr/1975_2001).
2. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level 4.0 ng per milliliter. The New England Journal of Medicine 2004; 350(22):22392246.
3. Keetch DW, Catalona WJ, Smith DS. Serial prostatic biopsies in men with persistently elevated serum prostate specific antigen values. The Journal of Urology 1994; 151(6):15711574.

• National Cancer Institute Fact Sheet 4.20, Selenium and Vitamin E Cancer Prevention Trial (SELECT): Questions and Answers
• National Cancer Institute Fact Sheet 5.18, Tumor Markers
• National Cancer Institute Fact Sheet 5.23, Early Prostate Cancer: Questions and Answers
• Understanding Prostate Changes: A Health Guide for All Men
• What You Need To Know About Prostate Cancer

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