PSA levels and testing

Prostate-specific antigen (PSA) is a protein produced by both normal cells and cancer cells of the prostate gland. This means even without cancer, a man will have a level of PSA.

What is a PSA test?

The PSA test is a blood test that measures a protein that is produced by normal healthy prostate cells and cancerous prostate cells.   

PSA levels in the blood are often high among men with prostate cancer, but there’s no clear-cut abnormal or normal PSA level because it can vary from person to person. PSA screening isn’t appropriate for everyone. The American Cancer Society recommends consulting first with a doctor. The decision to have a PSA test should be made after considering the uncertainties surrounding PSA testing, as well as the potential risks and benefits. 

However, if a man does have prostate cancer, PSA testing may be a valuable monitoring tool. 

PSA levels and how they can vary

Experts’ views regarding PSA levels have changed over the years.  

Previously, PSA levels of 4.0 ng/mL (nanograms per milliliter) and lower were considered normal. For men with test results showing levels above 4.0 ng/mL, doctors would recommend a prostate biopsy. But in more recent years, studies have demonstrated that some men with PSA levels lower than 4.0 ng/mL can have prostate cancer, and many men with PSA levels higher than 4.0 ng/mL don’t have prostate cancer.  

Moreover, a number of factors can cause PSA levels to fluctuate. Prostatitis, urinary tract infections, prostate biopsies, and prostate surgery may also cause PSA levels to rise. On the other hand, certain drugs can cause PSA levels to decrease, such as finasteride (Proscar®) and dutasteride (Avodart®).   

Generally, the higher the PSA level, the more indicative it is of prostate cancer, and an ongoing rise in PSA levels may also signal prostate cancer.  

• Men whose PSA level is between 4.0 ng/mL and 10 ng/mL have a one in four chance of having prostate cancer. 
• When a PSA level is over 10 ng/mL, there is a more than 50 percent chance of having prostate cancer.

Risk factors that can affect PSA levels

There are many other risk factors that can raise PSA levels, including:

• Enlarged prostate, also called benign prostatic hyperplasia (BPH), which is common in older men
• Older age, which naturally results in higher PSA levels
• Ejaculation within one to two days of the blood draw
• Riding a bicycle, which may raise levels for a short time after
• Certain urologic procedures, like cystoscopy
• Certain medicines, such as male hormones

Factors that may specifically lower PSA levels—even among men with prostate cancer—include:

• 5-alpha reductase inhibitors, which treat BPH or other urinary symptoms
• Some medications, such as aspirin or statins
• Herbal mixtures or supplements, which could skew the results

In certain cases, a factor that lowers PSA may lower the risk of developing prostate cancer. In others, however, lowering the PSA level has no effect and could be harmful, as prostate cancer could go undetected if the level drops too far.

For all of these reasons, it’s important to speak with a doctor about factors that might apply when considering PSA blood testing and interpreting test results.

Prostate cancer screening recommendations

There are no firm screening recommendations for all men when it comes to screening for prostate cancer, because levels can fluctuate and results need to be interpreted with caution. Most medical organizations recommend that men consult with their doctors before deciding to undergo PSA screening. 

The American Cancer Society recommends that men discuss screening with their doctor at three points in their life. These include: 

• At age 40 for men who are at highest risk for prostate cancer (more than one first-degree relative who had prostate cancer at a young age) 
• At age 45 for men who are at high risk for prostate cancer (first-degree relative diagnosed before 65 or African-American heritage) 
• At age 50 for men who are at average risk of prostate cancer
  

How a PSA test is used for diagnosis

Typically, the PSA test is performed in conjunction with a digital rectal exam (DRE) for a more accurate picture of signs of cancer. During the DRE, your doctor will insert a gloved, lubricated finger into the rectum to feel for any bumps or hard areas on the prostate.  

If a patient chooses to undergo prostate cancer screening and high PSA levels are found:  

• The doctor may recommend a second PSA screening test to confirm results.  
• If the second result comes back with an elevated PSA level, the doctor might recommend continuing to have PSA tests and DREs to monitor any potential changes over time.
• There are several types of PSA tests that the doctor may order. Sometimes a percent-free PSA test is performed to help guide the doctor on whether or not a prostate biopsy is needed. This is because men with lower amounts of free PSA floating in the blood are more likely to have prostate cancer. The care team may also order other PSA test options such as complexed PSA, a Prostate Health Index (PHI) or 4Kscore^® Test.
• If PSA levels continue to go up—or if a suspicious lump is found during a DRE—more tests may be recommended to determine the cause.
• If prostate cancer is suspected, a prostate biopsy may be recommended. 

If the patient's PSA results are considered normal or low, and prostate cancer is unlikely, future screening is often based on the level at the time of testing. According to the American Cancer Society:  

• If the PSA level is below 2.5 ng/mL, testing every two years may be recommended. 
• If the PSA level is higher than 2.5 ng/mL, yearly testing may be recommended. 

PSA test types

PSA tests may help patients decide whether or not to undergo a prostate biopsy to check for cancer. Patients and their doctors should discuss the pros and cons of each of these tests and what the results mean. Types of PSA tests include those below.

Percent-free PSA

This test may be ordered for men whose PSA blood test results were borderline (ranging between four and 10). Two major forms of PSA are found in the blood. One attaches to proteins in the blood, and one circulates freely. This test measures the ratio of freely circulating PSA compared to the total PSA. Men who have prostate cancer tend to have a lower percentage of free PSA—10 percent or less. Doctors are likely to recommend a prostate biopsy for men who have a percent-free PSA between 10 and 25 percent. However, not all doctors agree on the cutoff percentages, and the cutoff may change depending on the patient’s overall PSA.

Complexed PSA

This test is the opposite of the percent-free PSA. It measures the amount of PSA that attaches to other proteins in the blood rather than the percent of freely circulating PSA. While it provides similar information, it isn’t used as widely as percent-free PSA.

Prostate Health Index and 4Kscore^® Test

These are tests that combine different types of PSA. The goal is to get an overall score that helps detect whether the patient has prostate cancer that requires treatment.

The Prostate Health Index (PHI) combines:

• Total PSA
• Free PSA
• ProPSA, a PSA protein detected in the peripheral zone of the prostate gland that can therefore may be more useful in distinguishing between those with prostate cancer and those who have benign prostatic hyperplasia (BPH)–also known as a noncancerous enlarged prostate

The 4Kscore Test combines the results of:

• Total PSA
• Free PSA
• Intact PSA
• Human kallikrein 2 (hK2) (intact and hK2 are two additional novel markers that can be studied)
• Other factors such as patient’s age and biopsy history

The tests that combine types of PSA are often for men with a slightly elevated PSA who are trying to decide whether they should have a prostate biopsy. Also, they may be ordered for men who previously had a biopsy that was negative for cancer to determine if they need another.

PSA velocity

This isn’t a separate test. Rather, it takes a PSA and measures how quickly the PSA rises over time. PSA levels slowly go up with age. Some studies suggest that levels rise faster in men who have prostate cancer. However, research hasn’t shown that the man’s PSA velocity is more indicative of prostate cancer than the PSA itself. That’s why the American Cancer Society doesn’t recommend using PSA velocity as a screening tool for prostate cancer.

PSA density

The larger the prostate gland, the higher PSA levels tend to be. Some doctors use the PSA density (PSAD) measure to account for a higher PSA level in men with large prostates. A transrectal ultrasound is used to measure the volume (or size) of the prostate. The density is determined by dividing the PSA number by the prostate volume. The higher the PSA density, the more likely prostate cancer is present. However, PSA density hasn’t proven to be help as much as other tests such as the percent-free PSA test.

Age-specific PSA ranges

As men age, their PSA tends to rise. Doctors are more concerned about men with borderline PSAs who are in their 50s than men with borderline PSAs who are in their 80s. Some doctors suggest that a man’s PSA results should be compared to others in his age group. The usefulness of age-specific PSA has not been determined, and some professional societies recommend against using it as a deciding factor.

How a PSA test is used for cancer care

If the patient has prostate cancer, PSA testing, along with other results, may help the doctor determine:  

• The prostate cancer stage
• If other scans, tests or prostate cancer treatments are needed 
• How well the treatments are working, among other post-treatment monitoring needs