Prostate Specific Antigen (PSA)

Carolyn Vachani, MSN, RN, AOCN
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 29, 2007

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Prostate cancer is the most common cancer diagnosis in men. According to the American Cancer Society, an estimated 218,890 men will be diagnosed with prostate cancer in 2007. This accounts for nearly 30% of all cancer cases in men. It is not clear why, but the rates of prostate cancer are much higher in African American men than white men.

Screening for prostate cancer became much more common after the development of the serum prostate specific antigen (PSA) blood test in the late 1980s. In fact, there was a rapid increase in the number of cases reported from 1988-1992, which was a result of more cases being detected by the new test. There was a sharp decline in cases from 1992-1995, which was likely because doctors had “caught up” with all the undiagnosed cases in the previous years. The number of cases per year stabilized in the 10 years following this decline.

Screening for prostate cancer currently consists of two tests: a digital rectal exam (DRE) and a prostate specific antigen (PSA) blood test. Most prostate cancers grow very slowly, and it is not clear that screening men for prostate cancer actually always saves lives. We know that this testing detects some cancers that are very slow growing and may not every cause harm to the man, while other cancers that are picked up could result in death. There are two large trials currently looking at the efficacy of PSA testing (one in the US and one in Europe).

Whether or not a man will die from his prostate cancer is dependent on how aggressive the cancer is, how early it is detected, how well it is treated, and the man’s age and health status from other medical conditions. Most experts agree that men over age 75 or those with poor medical health have less to gain from a PSA test.

A digital rectal exam is done in your doctor’s office. Because your prostate is so close to your rectum, your doctor can feel it by inserting a gloved, lubricated finger into your anus. Your doctor can feel if there are lumps, asymmetries, or if your prostate is enlarged. A digital rectal exam is uncomfortable, but should not be painful. It is a useful test, but it is not perfect because some small cancers may not be felt since only the bottom and sides of the prostate can be examined in this manner. Although it isn't a perfect test, the digital rectal exam becomes more useful when it is combined with another test called a PSA.

A PSA (prostate specific antigen) test is a blood test that measures a protein called PSA, which is only made by the prostate gland (hence the term specific). PSA is a part of ejaculate material and is important to help increase sperm motility. Normal prostate tissue makes a little bit of PSA, but prostate cancer usually makes much more. By checking to see if your PSA level is elevated, a doctor can screen you for prostate cancer. However, the PSA test isn't perfect either, because some tumors won’t elevate the PSA, while some other processes (like benign prostatic hyperplasia and prostatitis) can cause it to be falsely elevated. Remember, the “specific” in prostate specific antigen stands for specific to the prostate gland, not specific to prostate cancer. However, the higher your PSA level is, the more likely the elevation is to be caused by a prostate cancer.

The level considered “normal” is less than 4.0 ng/ml. Experts do not agree on what level is high enough to do further testing (i.e. biopsy or ultrasound). Some feel that a level of 4 should lead to a biopsy, while others feel a level above 2.5 should lead to a biopsy. More important than a single PSA value is the trend of the PSA over time. If the level increases over time, regardless if it is above 4, further testing may be done to rule out cancer. Studies have shown that men who have a steady increase in their PSA are more likely to have prostate cancer and if the rise is rapid, it is more likely to be an aggressive cancer.

There are a number of specialized PSA tests which are used to help differentiate between elevated PSA due to benign conditions and those due to prostate cancer, or to determine the likelihood of cancer and the need for a biopsy. The free PSA test evaluates the ratio between the PSA that is free in the blood and the PSA that is bound to proteins in the blood. In most men, the majority of PSA is bound to proteins in the blood. Studies have found that the percentage of free PSA is lower in men with prostate cancer, compared with those without the disease. This test is approved by the US Food & Drug Administration for use in men with PSA levels between 4 and 10 ng/ml. A large study found that using a free PSA of 25% or less as a cut off for performing biopsy, resulted in the ability to find 95% of cancers in the study group.

PSA is found in the blood in free and bound (or complex) forms. Whereas free PSA measures the free PSA in the blood, a test called complex PSA measures the bound form of PSA. In essence, the traditional PSA test is made up of free PSA and complex PSA. The complex PSA test gives similar information in determining the need for biopsy just like the free PSA test. The advantage is that while the free PSA test requires two tests in the laboratory, the complex test requires only one. We may see this test used more in the future.

The PSA velocity is used to describe the speed at which the PSA value increases over a series of blood tests (and time). The result is reported as an amount (ng/ml) per year. A series of three tests over a period of a minimum of 18 months is needed to calculate a PSA velocity. In general, a rate of 0.75 ng/ml/year is considered high and may be a sign of a more aggressive cancer. Very high levels are more likely a sign of prostatitis than prostate cancer and can be treated with antibiotics.

The PSA density is used to evaluate the level of PSA in relation to the overall size of the prostate gland. This is done by a transrectal ultrasound to determine the size of the prostate and then dividing this number into the PSA value. The theory is that a rise in PSA can be directly proportional to an increase in prostate size. This test is not used very often; as it has not been proven to be reliable, while other tests are more reliable and less costly. One of the major concerns is the poor reliability of transrectal ultrasound in measuring prostate volume correctly.

There are several conditions that can increase the PSA that are not cancer, including benign prostatic hypertrophy (BPH) and prostatitis. Any irritation of the prostate can also cause an elevation. For this reason, men are asked to refrain from ejaculation for 48 hours before the test, and the PSA level should be drawn before the digital rectal exam is performed. A group of medications called 5-alpha reductase inhibitors (finasteride, dutasteride) that are used to treat BPH can cause a false reduction of up to 60% in the PSA level. Saw Palmetto (an herbal supplement) may also affect PSA levels.

The decision to have prostate cancer screening is something each man should discuss with his healthcare provider. Family history, race and health status plays a role in determining when and if screening should be performed. The American Cancer Society currently recommends:

  • PSA and DRE yearly, beginning at age 50
  • Men at high risk, including African American men, and any man with a first degree relative (father brother son), diagnosed with the disease before age 65 should begin screening at age 45
  • Men at highest risk (those with several first degree relatives diagnosed at an early age), should begin screening at age 40. Depending on the results, further testing may not be needed until age 45

Study confirms panel would lower biopsy rate, though it would miss a few high-grade cancers

Apr 29, 2010 - As has been reported previously, in men with elevated prostate-specific antigen, a panel of four kallikrein forms in serum -- total, free and intact PSA, and kallikrein-related peptidase 2 -- may predict the result of biopsy and help reduce unnecessary biopsy rates, according to a replication study published online April 26 in the Journal of Clinical Oncology.

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