Scientists are investigating ways to improve the PSA test to give doctors the ability to better distinguish cancerous from benign conditions and slow-growing cancers from fast-growing, potentially lethal cancers. And other potential biomarkers of prostate cancer are being investigated. None of these tests has been proven to decrease the risk of death from prostate cancer. Some of the methods being studied include
Free versus total PSA. The amount of PSA in the blood that is “free” (not bound to other proteins) divided by the total amount of PSA (free plus bound) is denoted as the proportion of free PSA. Some evidence suggests that a lower proportion of free PSA may be associated with more aggressive cancer.
PSA density. The blood level of PSA divided by the volume of the prostate gland. Some evidence suggests that this measure may be more accurate at detecting prostate cancer than the standard PSA test.
PSA velocity and PSA doubling time. PSA velocity is the rate of change in a man’s PSA level over time, expressed as ng/mL per year. PSA doubling time is the period of time over which a man’s PSA level doubles. These measures are most useful in men with a biochemical recurrence following surgery or radiation therapy.
Pro-PSA. Pro-PSA refers to several different inactive precursors of PSA. There is some evidence that pro-PSA is more strongly associated with prostate cancer than with BPH. One blood test combines the measurement of a form of pro-PSA called [-2]proPSA with measurements of PSA and free PSA into a mathematical formula called the Prostate Health Index. The resulting “phi score” calculated from this formula can be used to help a man with a PSA level between 4 and 10 ng/mL decide whether he should have a biopsy.
IsoPSA. PSA exists in different structural forms (called isoforms) in the blood. The IsoPSA test, which measures the entire spectrum of PSA isoforms rather than the concentration of PSA in the blood, may be better than traditional PSA testing for identifying men with an increased risk for developing high-grade prostate cancer who should undergo biopsy (11).
4Kscore Test. The 4Kscore test takes into account four different prostate-specific biomarkers, namely, total PSA, free PSA, intact PSA, and human kallikrein 2, as well as the patient’s age, prior biopsy history, and DRE status to assess the risk of aggressive prostate cancer in someone with an abnormal screening result.
Urinary biomarkers. Prostate cancer antigen 3 (PCA3) mRNA and the TMPRSS2-ERG gene fusion are biomarkers that are tested in a urine sample. They have increased specificity for prostate cancer compared with PSA testing alone, but do not appear to preferentially identify clinically significant disease. The use of these two biomarkers in combination can help reduce the number of (unnecessary) biopsies.