Prostate Cancer Diagnosis
Researchers have developed several ways to improve the PSA test's accuracy. These improvements include
- assessing PSA level in relation to prostate size (PSA density)
- monitoring annual changes in PSA (PSA velocity)
- measuring the ratio of free to total PSA (percent free PSA); and
- adjusting the PSA result for a patient's age (age-specific PSA)
None of these take the place of a simple PSA measurement for screening.
This measurement takes the size of a man's prostate into account 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 BPH and prostate cancer.
The higher the PSA density, the greater the chance of cancer, because the elevated PSA level is less likely to be the result of benign prostate enlargement. Several studies have found that a PSA density greater than 0.15 indicates a higher risk of cancer. PSA density appears most useful in diagnosing prostate cancer in men with PSA levels between 4 ng/mL and 10 ng/mL.
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 from Johns Hopkins and the National Institute on Aging found that an increase in PSA level of more than 0.75 ng/mL per year was an early predictor of prostate cancer in men with PSA levels between 4 ng/mL 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 most useful in predicting the presence of cancer when changes in PSA are evaluated over at least one to two years.
In a study reported in The New England Journal of Medicine, a rapid rise in PSA level (more than 2 ng/mL) in the year before prostate cancer diagnosis and surgical treatment predicted a higher likelihood that a man would die of his cancer over the next seven years. Moreover, a Johns Hopkins study published in the Journal of the National Cancer Institute found that a man's PSA velocity 10 to 15 years before he was diagnosed with prostate cancer predicted his survival from the disease 25 years later.
In the study, 92 percent of men with an earlier PSA velocity of 0.35 ng/mL or less per year had survived, compared with 54 percent of men whose PSA velocity was greater than 0.35 ng/mL.
Percent free PSA or complexed (bound) PSA
PSA in the blood is either bound (attached) to proteins (known as complexed) or unbound (known as free). PSA assays usually measure the total PSA (both free and complexed). Other assays measure the percentage of free PSA or the percentage of complexed PSA. Compared with men with BPH, men with prostate cancer have a higher percentage of complexed PSA and a lower percentage of free PSA.
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. Using the percent free PSA result to help determine the need for biopsy might help reduce the number of unnecessary biopsies.
Research suggests that in men with PSA levels between 4 ng/mL and 10 ng/mL, performing a prostate biopsy only when the percent free PSA is 24 percent or below would detect more than 90 percent of prostate cancers while reducing the number of unnecessary biopsies by 20 percent.
In addition, some investigators support using complexed PSA measurements to detect cancer, believing that this provides the same information as free PSA and total PSA. Percent free or complexed PSA, as well as PSA density and PSA velocity, also can be used to determine the need for a repeat prostate biopsy when the initial biopsy shows no evidence of cancer but cancer is still suspected.
PSA increases with age because the prostate gradually enlarges as men grow older. Some years ago, researchers suggested adjusting PSA levels to the age of the patient: Higher levels would be considered normal in older men, and lower levels considered normal in younger men.
However, the concern is that the use of higher PSA thresholds in older men will miss important cancers. As noted previously, physicians should suspect prostate cancer at lower levels (above 2 ng/mL) or when PSA is rising at all in men in their 40s.
Biomarkers are substances like PSA that can be measured in a body fluid and used to detect or monitor a disease. Prostate cancer researchers are testing several potential biomarkers to supplement the use of PSA in prostate cancer screening. It is likely that new markers, including the presence or absence of genetic variants, will be used in combination to predict the overall risk of prostate cancer, allowing better identification of those who should undergo a prostate biopsy.