The blood level of PSA is often elevated in people with prostate cancer, and the PSA test was originally approved by the FDA in 1986 to monitor the progression of prostate cancer in men who had already been diagnosed with the disease. In 1994, FDA approved the PSA test to be used in conjunction with a digital rectal exam (DRE) to aid in the detection of prostate cancer in men 50 years and older. Until about 2008, many doctors and professional organizations had encouraged yearly PSA screening for prostate cancer beginning at age 50.
PSA testing (along with a DRE) is also often used by health care providers for individuals who report prostate symptoms to help determine the nature of the problem.
In addition to prostate cancer, several benign (not cancerous) conditions can cause a person’s PSA level to rise, particularly prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (BPH) (enlargement of the prostate). There is no evidence that either condition leads to prostate cancer, but someone can have one or both of these conditions and develop prostate cancer as well.
Is the PSA test recommended for prostate cancer screening?
Beginning around 2008, as more was learned about both the benefits and harms of prostate cancer screening, a number of professional medical organizations began to caution against routine population screening with the PSA test. Most organizations recommend that individuals who are considering PSA screening first discuss the risks and benefits with their doctors.
Some organizations do recommend that men who are at higher risk of prostate cancer begin PSA screening at age 40 or 45. These include Black men, men with germline variants in BRCA2 (and to a lesser extent, in BRCA1), and men whose father or brother had prostate cancer.
In 2018, the United States Preventive Serves Task Force (USPSTF) updated its recommendation statement for prostate cancer screening from a “D” (not recommended) to a “C” (selectively offering PSA-based screening based on professional judgment and patient preferences) in men ages 55 to 69. (The USPSTF continues to recommend against PSA screening for men 70 years and older.) The updated recommendation, which applies to the general population as well as those at increased risk due to race/ethnicity or family history, is as follows:
- For individuals ages 55 to 69 years, the decision to undergo periodic PSA-based screening for prostate cancer should be an individual one. Before making the decision, a person should discuss the potential benefits and harms of screening with their clinician and consider these in the context of their own values and preferences.
- PSA-based screening for prostate cancer is not recommended for individuals 70 years and older.
Currently, Medicare provides coverage for an annual PSA test for all Medicare-eligible individuals ages 50 and older. Many private insurers cover PSA screening as well.
What are some of the limitations and potential harms of the PSA test for prostate cancer screening?
Detecting prostate cancer early may not reduce the chance of dying from prostate cancer. When used in screening, the PSA test can help detect small tumors. Having a small tumor found and treated may not, however, reduce the chance of dying from prostate cancer. That is because many tumors found through PSA testing grow so slowly that they are unlikely to be life-threatening. Detecting such tumors is called “overdiagnosis,” and treating them is called “overtreatment.”
Overtreatment exposes a person unnecessarily to the potential complications associated with prostate surgery and radiation therapy. These include urinary (e.g., urinary incontinence, or leaking of urine following surgery and increased frequency and urgency of urination following radiation), gastrointestinal (e.g., loose stools or, less commonly, rectal bleeding following radiation), and sexual side effects (loss of erections or decreased erections following both surgery and radiation).
In addition, finding cancer early may not help someone who has a fast-growing or aggressive prostate tumor that may have spread to other parts of the body before being detected.
The PSA test may give false-positive results. A false-positive test result occurs when the PSA level is elevated but no cancer is actually present. A false-positive test result may create anxiety and lead to additional medical procedures, such as a prostate biopsy, that can be harmful. Possible side effects of biopsies include serious infections, pain, and bleeding.
False-positive test results are common with PSA screening; only about 25% of people who have a prostate biopsy due to an elevated PSA level are found to have prostate cancer when a biopsy is done.
How are researchers trying to improve the PSA test?
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 is 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 a biopsy.
- 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.