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Old 07-14-2018, 10:00 AM
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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
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