The introduction of the prostate specific antigen (PSA) test in 1986 ushered in a new era in prostate cancer detection and treatment. With the ability to find cancer up to six years earlier than with a digital rectal exam, PSA testing has resulted in more men than ever being diagnosed with tumors still in an early, localized, and curable stage. Before the PSA test was introduced, more than half of prostate cancers were not detected until they had already advanced beyond the prostate; but today, the majority of cancers (about 70%) are still localized when they are detected.

Even though prostate cancer mortality rates have fallen by 6% since 1992, it is unclear whether this decrease is due to the widespread use of PSA. A positive effect is suggested by the fact that groups of men who are more intensively screened (for example, white men) have had a more significant decrease in mortality than those not as heavily screened (for example, black men). Still, experts remain divided on the appropriateness of PSA screening in men with no symptoms of prostate cancer. While acknowledging that screening improves the odds of detecting curable cancer, some contend that many of these cancers are inconsequential -- which means that many men undergo needless, and potentially harmful, treatments. To address such concerns, researchers have developed -- and continue to work on -- refinements to the PSA test.

Recommendations for Testing

The American Urological Society, the American Cancer Society, and the American College of Physicians recommend that prostate cancer screening be discussed with all men over age 50 and with high-risk men -- that is, black men or any man with a family history of prostate cancer -- over age 40 to 45. In general, a PSA value of 4 ng/mL is considered the cut-off for suspected cancer (although it may vary slightly by age), and levels above 10 ng/mL indicate very high risk. It is values between 4 and 10 ng/mL that are the most ambiguous; men in this range may benefit most from refinements in the PSA test. The risk of cancer based on PSA levels follows:

PSA levels under 4 ng/mL: "normal"
4 to 10 ng/mL: 20 to 30% risk
10 to 20 ng/mL: 50 to 75% risk
Above 20 ng/mL: 90%.

Factors Influencing PSA Results

An enzyme that is normally present in high concentration in seminal fluid, PSA serves as a tumor marker because it shouldn't be present in high concentration in the bloodstream. Therefore, high levels of PSA in the blood indicate an abnormality in the prostate -- which may be due to cancer or other causes, such as BPH or prostate infection. One of the main drawbacks of PSA testing for cancer is that other factors may trigger a rise in PSA. In addition to being sensitive (meaning a test can detect cancer most of the time, or have few false-negative results), an effective screening tool must also be specific, which means that it doesn't falsely identify cancer (false-positive results) and prompt a needless biopsy.

In general, the PSA test is sensitive, though levels can be misleadingly lowered by the use of finasteride (Proscar) for BPH. A six-month course of the drug can lower PSA levels by 50%. To account for such an effect, doctors routinely double PSA levels of men who have taken finasteride for an extended period.

More often, PSA gives a false-positive result, possibly due to BPH or some other factor. Urological difficulties, such as prostatitis or urinary retention, and invasive procedures, such as a prostate biopsy, may raise PSA levels. Therefore, experts recommend waiting up to four to six weeks after significant events, such as a biopsy, or a few days for lesser events before having a PSA test. For men over age 50, ejaculation within the past two days may artificially raise PSA levels. Though it's not necessary to avoid sex before a PSA test, men should be aware of the time of their last ejaculation in case results are high. Finally, while DRE or other aspects of a prostate exam shouldn't interfere with PSA levels, doctors recommend that blood be drawn before the rectal exam as a precaution.

Refining the PSA Test

To avoid false-positive results, researchers have developed several refinements in PSA testing over the past decade.

• PSA density is used to help differentiate between cancer and BPH in men with moderately high PSA levels (4 to 10 ng/mL) and normal DRE results. Cancer causes a greater elevation in PSA per prostate volume than BPH -- which means PSA density should be higher in men with cancer. To find PSA density, doctors divide the PSA results by prostate volume (as estimated by transrectal ultrasound). This method is imperfect, but studies showing that PSA density levels over 0.15 indicate a high risk of cancer have led doctors to use PSA density tests for men with PSA levels between 4 and 10 ng/mL.

• PSA velocity monitors changes in PSA over time. PSA levels rise more rapidly in men with prostate cancer than in other men. To be most effective, PSA should be measured at least three times over a two-year period to calculate PSA velocity. Research has found that about 70% of men with a PSA velocity of 0.75 ng/mL or greater have cancer when PSA is 4 to 10 ng/mL. But only about 50% of men with a PSA velocity below 0.75 ng/mL per year have cancer. The test is used primarily to determine the need for a repeat biopsy in those with PSA levels between 4 to 10 ng/mL and a prior negative biopsy.

• Age-specific PSA levels have been suggested for younger men, because PSA levels usually rise with age. Thus, while 2 ng/mL may be normal in a 60-year old, this level is more likely to signify cancer in men between ages 40 and 49. Since research has yet to show that using age-specific PSA values will increase the detection of curable cancers, for now the standard cut-off of 4 ng/mL is still considered preferable for men between age 50 and 70.

• Percent free PSA is the ratio of free (unbound) PSA to bound (attached to proteins) PSA in the blood. Men with prostate cancer have a lower percent free PSA than men without cancer. Measuring the ratio of free to total PSA appears to be particularly promising for eliminating unnecessary biopsies in men with PSA levels between 4 and 10 ng/mL.

Link: Understanding PSA, from Johns Hopkins