Prostate-specific antigen (PSA) is a normal and harmless protein produced by cells within the prostate gland. The protein is excreted in the semen and its purpose is to improve the fertility of the sperm. Small amounts of PSA can be detected in the bloodstream of normal males by means of a simple blood test. The PSA level is often elevated in men with prostate cancer and in other disorders of the prostate, and is therefore a useful tool for diagnosing prostate cancer. It can also aid in the diagnosis of certain benign conditions of the prostate gland, such as benign prostatic enlargement and bacterial infections.

Serum PSA is the most effective test currently available for the early detection of prostate cancer. It is more sensitive than the digital rectal exam. In fact, the prostate often feels perfectly normal in early prostate cancer. However, the effectiveness of PSA testing remains controversial because prostate cancer will be found in only around 35% of men with elevated levels of PSA. Also, prostate cancer may be relatively harmless in older men in its early stages, so early detection is not necessarily a priority in those individuals. PSA testing is not always warranted in elderly men who have no urinary symptoms.

The free PSA test may improve the accuracy of PSA testing in those patients with mildly increased PSA levels. Free PSA measures the portion of PSA in the blood that is not attached to circulating proteins, and when expressed as a ratio of free to total PSA level, may aid in the diagnosis of prostate cancer. When the percentage of free PSA is low, the chance of having prostate cancer is higher. Patients with high free PSA percentages are less likely to have prostate cancer, and prostate biopsy may be avoided in many individuals with high free PSA ratios. Also a useful tool is the trend in PSA levels over time, sometimes called PSA velocity. A high rate of PSA increase may suggest the presence of prostate cancer and in men with known prostate cancer, a high rate of PSA increase suggests a worse prognosis.

The usefulness of PSA testing depends on the intelligent interpretation of the results, and PSA levels must be considered in relation to the patient's age, other medical conditions, the degree of prostate enlargement, certain medications and numerous other factors. The urologist is trained to take all of these factors into consideration when making treatment decisions. Also, a high PSA level alone cannot make a diagnosis of prostate cancer. Only a biopsy of the prostate can definitively establish that diagnosis.

PSA is especially useful for following patients with known prostate cancer. A high PSA at the time of diagnosis indicates a worse prognosis. Some elderly patients with prostate cancer do not require treatment, just watchful waiting, and PSA levels can tell the physician when the cancer starts to progress. At a certain level of PSA, treatment could become necessary in those individuals. In patients already treated for prostate cancer with radiation, surgery, or medication, serial PSA levels are checked along with digital rectal examinations to monitor for recurrence.