Improvements to the PSA

Researchers have developed several ways to improve the ability of PSA to detect prostate cancer. These refinements include:

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• Assessing PSA in relation to prostate size (PSA density)
  PSA density takes into account the size of a man's prostate when evaluating his PSA level. It is calculated by dividing the PSA value by the size of the prostate (as determined by transrectal ultrasound). This measurement helps doctors distinguish between benign prostatic hyperplasia (BPH) and cancer: The higher the PSA density, the greater the chance of cancer, because elevated PSA is less likely the result of prostate enlargement. According to several studies, a PSA density greater than 0.15 indicates a higher risk of cancer. PSA density appears most useful for diagnosing prostate cancer in men with PSA levels between 4 and 10 ng/mL.
• Monitoring annual changes in PSA (PSA velocity)
  This measurement takes into account annual changes in PSA values, which rise more rapidly in men with prostate cancer than in men without the disease. A study found that an increase in PSA levels of greater than 0.75 ng/mL per year was an early predictor of prostate cancer in men with PSA levels between 4 and 10 ng/mL. PSA velocity is especially helpful in detecting early cancer in men with mildly elevated PSA levels and a normal digital rectal exam; it is not useful in predicting the presence of cancer unless changes in PSA are evaluated over at least 1 1/2 to 2 years.
• Measuring the ratio of free to total PSA (percent free PSA)
  PSA in the blood is either bound (attached to proteins) or unbound (free). Men with prostate cancer have a higher percentage of bound PSA and a lower percentage of free PSA than men with benign prostatic hyperplasia (BPH). Research suggests that determining the ratio of free to total PSA in the blood helps distinguish between PSA elevations due to cancer and those caused by BPH. In men with PSA levels between 4 and 10 ng/mL, performing a prostate biopsy only when the percent free PSA is 24 percent or below would result in the detection of 90 percent of prostate cancers and reduce by 20 percent the number of unnecessary biopsies. Percent free PSA, as well as PSA density and PSA velocity, can also be used to determine the need for a repeat biopsy when the initial biopsy shows no evidence of cancer but cancer is still suspected.
• Adjusting PSA for a patient's age (age-specific PSA)
  PSA increases with age because the prostate gradually enlarges as men grow older. Some years ago, researchers suggested adjusting PSA levels for the age of the patient: Higher levels would be considered normal in older men and lower levels considered normal in younger men. However, research has not shown that using lower levels to prompt biopsy in younger men increases the likelihood of finding curable cancers, nor that using higher levels in older men interferes with the chance of detecting curable cancers. For now, a level of 4 ng/mL is considered the upper limit of normal in men age 50 and older. For men younger than age 50, the upper limit of normal is 2.5 ng/mL.