Prostate-specific antigen (PSA) is a protein produced by cells of the prostate gland. The PSA test measures the level of PSA in the blood. The doctor takes a blood sample, and the amount of PSA is measured in a laboratory. Because PSA is produced by the body and can be used to detect disease, it is sometimes called a biological marker or a tumor marker.

It is normal for men to have a low level of PSA in their blood; however, prostate cancer or benign (not cancerous) conditions can increase a man’s PSA level. As men age, both benign prostate conditions and prostate cancer become more common. The most frequent benign prostate conditions are prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (BPH) or enlargement of the prostate. There is no evidence that prostatitis or BPH causes cancer, but it is possible for a man to have one or both of these conditions and to develop prostate cancer as well.

A man’s PSA level alone does not give doctors enough information to distinguish between benign prostate conditions and cancer. However, the doctor will take the result of the PSA test into account when deciding whether to check further for signs of prostate cancer.

The U.S. Food and Drug Administration (FDA) has approved the use of the PSA test along with a digital rectal exam (DRE) to help detect prostate cancer. During a DRE, a doctor inserts a gloved finger into the rectum and feels the prostate gland through the rectal wall to check for bumps or abnormal areas. Doctors often use the PSA test and DRE as prostate cancer screening tests; together, these tests can help doctors detect prostate cancer in men who have no symptoms of the disease 

What are some of the limitations of the PSA test?

PSA testing may identify very slow-growing tumors that are unlikely to threaten a man's life. Also, PSA testing may not help a man with a fast-growing or aggressive cancer that has already spread to other parts of his body before being detected.

False-positive tests. False-positive test results (also called false positives) occur when the PSA level is elevated but no cancer is actually present. False positives may lead to additional medical procedures that have potential risks and significant financial costs and can create anxiety for the patient and his family. Most men with an elevated PSA test result turn out not to have cancer; only 25 to 35 percent of men who have a biopsy due to an elevated PSA level actually have prostate cancer.

False-negative tests. False-negative test results (also called false negatives) occur when the PSA level is in the normal range even though prostate cancer is actually present. Most prostate cancers are slow-growing and may exist for decades before they are large enough to cause symptoms. Subsequent PSA tests may indicate a problem before the disease progresses significantly.

Scientists are also researching ways to improve the PSA test, hopefully to allow cancerous and benign conditions, as well as slow-growing cancers and fast-growing, potentially lethal cancers, to be distinguished from one another. Some of the methods being studied include the following:

• PSA velocity: PSA velocity is the change in PSA level over time. A sharp rise in the PSA level raises the suspicion of cancer and may indicate a fast-growing cancer. A 2006 study found that men who had a PSA velocity above 0.35 ng/mL per year had a higher relative risk of dying from prostate cancer than men who had a PSA velocity less than 0.35 ng/mL per year. More studies are needed to determine if a high PSA velocity more accurately detects prostate cancer early.
• PSA density: PSA density considers the relationship between the level of PSA and the size of the prostate. In other words, an elevated PSA level might not arouse suspicion if a man has a very enlarged prostate. The use of PSA density to interpret PSA results is controversial because cancer might be overlooked in a man with an enlarged prostate.
• Free versus attached PSA: PSA circulates in the blood in two forms: Free or attached to a protein molecule. The free PSA test is more often used for men who have higher PSA values. Free PSA may help tell what kind of prostate problem a man has. With benign prostate conditions (such as BPH), there is more free PSA, while cancer produces more of the attached form. If a man’s attached PSA level is high but his free PSA level is not, the presence of cancer is more likely. In this case, more testing, such as a prostate biopsy, may be done. Researchers are exploring additional ways of measuring PSA and comparing these measurements to determine whether cancer is present.
• Alteration of PSA cutoff level: Some researchers have suggested lowering the cutoff levels used to determine whether a PSA measurement is normal or elevated. For example, a number of studies have used cutoff levels of 2.5 or 3.0 ng/mL (rather than 4.0 ng/mL). In such studies, PSA measurements above 2.5 or 3.0 ng/mL are considered suspicious. Researchers hope that using these lower cutoff levels will increase the chance of detecting prostate cancer; however, this method may also lead to unnecessary medical procedures.

What other methods are being studied to detect prostate cancer?

Researchers are investigating several other ways to detect prostate cancer that could be used alone or together with the PSA test and DRE. Some of these include the following:

• MicroRNA patterns: MicroRNAs are small, single-strand molecules of ribonucleic acid (RNA) that regulate important cellular functions. Some research suggests that the microRNA patterns in early-stage prostate cancer and late-stage prostate cancer may be different.
• Non-mutation gene alterations: The activity of a gene can be altered in ways that do not involve a change (mutation) to its DNA code. This can occur by modifying the gene’s DNA through a process known as methylation or by modifying the proteins that bind to the gene and help control how it is configured in the chromosome on which it is located. These types of gene alterations are called epigenetic alterations. Scientists hope to identify DNA methylation changes and protein modifications that will be able to identify prostate cancer early and help predict tumor behavior.
• Gene fusions: Sometimes genes on different chromosomes can come together inappropriately and fuse to form hybrid genes. These hybrid genes have been found in several types of cancer, including prostate cancer, and may play a role in cancer development. The gene fusions found in prostate cancer involve members of the ETS family of oncogenes, which are genes that cause cancer when mutated or expressed at higher than normal levels. 
• PCA3: PCA3, also known as DD3, is a prostate-specific RNA that is reported to be expressed at high levels in prostate tumor cells. It does not appear to contain the genetic code for a protein. A urine test for this RNA, to be used in addition to current prostate cancer screening tests, has the potential to be useful and is under study.
• Differential detection of metabolites: Molecules produced by the body’s metabolic processes, or metabolites, may be able to help distinguish between benign prostate tissue, localized prostate cancer, and metastatic prostate cancer.
• Proteo-imaging: Proteo-imaging is the ability to localize and follow changes at the molecular level, through imaging, of the protein distributions in specific tissues. Being able to see different patterns of protein expression in healthy prostate tissue versus abnormal prostate tissue may help classify early prostate changes that may one day lead to cancer.
• Protein patterns in the blood: Researchers are also studying patterns of proteins in the blood to see if they can identify one or more unique patterns that indicate the presence of prostate cancer and allow more aggressive cancers to be distinguished from less aggressive ones. 

It is important to note that screening cannot diagnose prostate cancer. Only a biopsy can diagnose prostate cancer. If cancer is suspected, a biopsy is needed to determine whether cancer is present in the prostate. During a biopsy, samples of prostate tissue are removed, usually with a needle, and viewed under a microscope.