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Low Free PSA Levels and Prostate Cancer

Medically Reviewed by Melinda Ratini, DO, MS on June 14, 2022

Many men are familiar with the routine: During your annual exam, your doctor slips on a glove and feels your prostate. The goal is to check this walnut-sized organ for lumps, hard spots, and other possible signs of cancer.

If your doctor finds something that doesn’t feel right, the next step may be a biopsy, which takes a sample of tissue for examination under a microscope. Another part of the screening for prostate cancer may include screening your blood for free prostate-specific antigen or PSA. Talk to your doctor to see if screening is right for you.

What Are PSA and Free PSA?

PSA a protein that makes semen more liquid-like. This makes it easier for sperm to reach a woman’s egg during sex.

It’s normal for a small bit of PSA to get into your bloodstream. If you have cancer or other prostate problems, more PSA will circulate in your blood.

But checking for PSA levels alone often can lead to false positive results for prostate cancer. Three out of 4 men with high overall PSA levels turn out to be cancer-free.

A more accurate way to predict prostate cancer is to also look for a second form of PSA called free PSA. The name comes from the fact that free PSAs flow through your blood solo, without being attached to other proteins as are regular PSAs.

The ratio of your free PSAs to your overall PSA levels can give a better picture about your prostate cancer risk. The amount of free PSA is lower in men who have prostate cancer. That’s the opposite of total PSA, high levels of which can be a sign of cancer. In two men with identical levels of total PSA, the one who has a lower amount of free PSA is more likely to have cancer.

One study found that free PSA levels as a percentage of total PSA may be the best way to diagnose prostate cancer.

Reasons for Low Free PSA Levels

Research has found several things that may play a role in your free PSA count.

Race and ethnicity. White and Asian men are more likely to have lower free PSA levels than African American men. White men who are not Hispanic also were more likely to have lower free PSA levels than those who considered themselves ethnically Hispanic.

Weight. Men who are overweight, particularly those who are very obese, tend to have lower free PSA levels.

Smoking. One study found that men who smoke or used to smoke have lower free PSA levels than those who never did.

Age. Younger men are more likely than those over 70 to have lower free PSA counts.

Enlarged prostate gland. This noncancerous condition, which can make it harder for you to pee, also may drop your free PSA count.

A low percentage of free PSAs to total PSAs also may be a sign that your cancer is more aggressive.

Total PSA and Free PSA Levels

There are no normal levels of total PSA or free PSA for men of any age. Different doctors may use different cutoff points to decide if you need a biopsy or other further testing.

A PSA test measures nanograms of PSA per milliliter (ng/mL) of blood. But if you have no symptoms, the usual guidelines for total PSA levels are:

  • Safe. Zero to 2.0 ng/mL. Your chance of prostate cancer is very low. Checking your free PSA level may be unneeded.
  • Safe for most. Below 4.0 ng/mL. Safe for most. About 15% of the men in this level have prostate cancer. A free PSA check may help your doctor or urologist decide if you might need a needle biopsy.
  • Borderline. Between 4 ng/mL and 10 ng/mL. About 25% of men in this group likely have cancer. Your doctor likely will order a free PSA test.
  • Dangerous. Above 10.0 ng/mL. The odds are better than 1 in 2 that you have prostate cancer. Your doctor likely will recommend a biopsy.

If your total PSA levels are in the borderline area between 4-10 ng/mL, your free PSA ratio can give you a more detailed picture of your cancer risk.

The chances that a needle biopsy will turn up prostate cancer varies by your free PSA concentration and your age:

Concentration of more than 25%: About 1 in 10 men ages 50 to 59 will have cancer. For those 70 and older, it’s 16%.

Concentration of 25%-19%: Cancer risk ranges from 18% to 30% for men 50 and older.

Concentration of 18%-11%: Probability of finding cancer is about 27% for those 50 to 59; 34% for men 60 to 69; and 41% for those 70 and older.

Concentration of less than 10%: Cancer risk is about 50% if you’re 50 to 59 years old; for those 70 and older, it’s 65%.

Even if your total PSA or free PSA levels fall outside the “normal” ranges, it doesn’t necessarily mean you have prostate cancer. It’s also possible for you to have cancer even if your biopsy is negative. Talk to your doctor or urologist about what types of screening may be best for you and to help you understand your test results.

Show Sources

SOURCES:

Mayo Clinic: “PSA test.”

Mayo Clinic Laboratories Neurology Catalog: “Prostate-Specific Antigen (PSA), Total and Free, Serum.”

Prostate Cancer Foundation: “The PSA Test.”

Prostate Cancer Free Foundation: “Prostate Specific Antigen PSA - Does Your PSA Indicate Cancer?”

ZeroCancer.org: “PSA Screening.”

Journal of Urology: “Rate of change in serum prostate specific antigen levels as a method for prostate cancer detection.”

Lima Memorial Health System Laboratory: “Prostate Specific Antigen (PSA), Total and Free, Serum.”

Japanese Journal of Clinical Oncology: “Significance of Free to Total PSA Ratio in Men with Slightly Elevated Serum PSA Levels: A Cooperative Study.”

Brazilian Journal of Medical and Biological Research: “Obesity inversely correlates with prostate-specific antigen levels in a population with normal screening results of prostate cancer in northwestern China.”

Medicine: “Value of free/total prostate-specific antigen (f/t PSA) ratios for prostate cancer detection in patients with total serum prostate-specific antigen between 4 and 10 ng/mL. A meta-analysis.”

Urology: “Relationship of demographic and clinical factors to free and total prostate-specific antigen,” “Free/total PSA ratio is a powerful predictor of future prostate cancer morbidity in men with initial PSA levels of 4.1 to 10.0 ng/mL,” “Comparison of analysis of the different prostate-specific antigen forms in serum for detection of clinically localized prostate cancer.”

Harvard Health Publishing: “What is the difference between PSA and free PSA?”

National Cancer Institute: “Prostate-Specific Antigen (PSA) Test.”

Cancer Network, Home of the Journal Oncology: “Percent Free PSA Test May Prevent Unnecessary Biopsies.”

American Cancer Society: “Screening Tests for Prostate Cancer.”

UptoDate: “Measurement of prostate-specific antigen.”

Anticancer Research: “Demographic and Clinical Factors as Determinants of Serum Levels of Prostate Specific Antigens and its Derivatives.”

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