Prostate-specific antigen (PSA) is a protein made mainly in the prostate. A bit of PSA is released into the bloodstream during each ejaculation, and PSA in ejaculate makes it easier for the semen to carry sperm to the fallopian tubes during conception.
PSA can have two basic states. It may be bound to another protein or float freely.
PSA, a protein produced by prostate gland cells, circulates through the body in two ways: either bound to other proteins or on its own. PSA traveling alone is called free PSA. The free-PSA test measures the percentage of unbound PSA; the PSA test measures the total of both free and bound PSA.
Prostate cancer can raise PSA levels, but so can other conditions. These include an enlarged prostate, prostatitis, and advancing age. In fact, studies have shown that about 75% of men with an elevated PSA do not have prostate cancer. To determine which men actually have cancer and which don’t, physicians traditionally perform a biopsy. Undergoing a biopsy isn’t as traumatic as surgery, but it does cause discomfort and can provoke anxiety.
Rather than subject everyone with an elevated PSA to a biopsy, some urologists measure free PSA in patients with a total PSA level between 4 ng/ml and 10 ng/ml. Studies have shown that men with a total PSA in this “gray area” and a free PSA greater than 25% are more likely to have a benign condition (=not harmful in effect) than to have cancer, making a biopsy unnecessary. Men with a total PSA in the same range (between 4 ng/ml and 10 ng/ml) and a free PSA below 10% need to have a biopsy. More likely than not, they have prostate cancer.
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The markers PSA, TOTAL; PSA, FREE; and PSA, % FREE are different measurements used in this context and have specific correlations and clinical implications.
PSA, TOTAL: This marker measures the total amount of PSA in the blood, which includes both PSA bound to proteins and PSA that is unbound (free PSA). Elevated total PSA levels can indicate prostate cancer, benign prostatic hyperplasia (BPH), or prostatitis (inflammation of the prostate). However, it is not specific to prostate cancer alone, leading to potential false positives.
PSA, FREE: This marker measures the amount of PSA in the blood that is not bound to proteins. The free PSA level can help differentiate between prostate cancer and benign conditions. Typically, men with prostate cancer have lower levels of free PSA relative to their total PSA because cancer tends to produce more bound PSA.
PSA, % FREE: This is the ratio of free PSA to total PSA, expressed as a percentage. It is calculated by dividing the free PSA by the total PSA and multiplying by 100. This percentage is particularly useful in improving the specificity of PSA testing for prostate cancer. A lower % free PSA suggests a higher likelihood of prostate cancer, whereas a higher % free PSA is more indicative of benign conditions like BPH.
The correlation among these markers lies in their combined use to enhance diagnostic accuracy. Total PSA gives an overall measure, while free PSA and % free PSA help refine the interpretation:
In clinical practice, these markers are used together to determine the need for further diagnostic procedures such as a prostate biopsy. By assessing both the total PSA and the proportion of free PSA, healthcare providers can better stratify patients' risk and make more informed decisions regarding the necessity of invasive tests and subsequent treatment plans.
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Doctors interpret PSA results based on several factors, including:
Total PSA:
Total PSA ranges may vary slightly. According to a review of studies, the normal ranges for total PSA in nanograms per milliliter (ng/mL) are:
age 49 or younger: 0.0–2.5 ng/mL
age 50 to 59: 0.0–3.5 ng/mL
age 60 to 69: 0.0–4.5 ng/mL
age 70 or older: 0.0–6.5 ng/mL
When total PSA levels are higher than the appropriate range, a person has an increased risk for prostate cancer. It does not show conclusively that a person has cancer. Doctors will then compare the results of this test with results of a free PSA test.
Free PSA ratio:
A high total PSA level and a low free PSA level generally indicate a risk for prostate cancer.
Free PSA ranges can vary, but in general, a higher ratio of free PSA to total PSA is healthier.
When the ratio of free to total PSA is between 0 and 10 percent, the risk of having cancer may be as high as 56 percent. When this ratio is greater than 25 percent, this risk reduces to 8 percent.
However, these results are not conclusive evidence for or against a cancer diagnosis, and a doctor may still want to do a tissue biopsy.
Other factors:
Doctors will consider additional factors, such as a person’s age, ethnicity, and prostate volume. For instance, PSA levels normally rise with age, and this can affect the results of the tests.
Other factors, called PSA kinetics, may also influence how a doctor views the results in people who are currently undergoing treatment for prostate cancer.
PSA kinetics reflect how levels change over time. It can be difficult to obtain a clear picture, but kinetics can play an important role in the outlook and treatment of prostate cancer. The factors involved are PSA velocity and doubling time.
PSA velocity measures how rapidly levels are rising, and it can indicate that prostate cancer is recurring.
Doubling time is a calculation of how long it takes for PSA levels to double. A faster doubling time can suggest a more aggressive cancer, which can be a sign that the cancer is spreading.
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What if my PSA, Total reading is normal, but my PSA, % Free reading is low?
A normal PSA, TOTAL (prostate-specific antigen) and a low PSA, % FREE can be a complex scenario that warrants careful interpretation. Here’s a detailed explanation:
Normal PSA, TOTAL:
- Definition: Generally, a PSA, TOTAL level below 4.0 ng/mL is considered within the normal range, though this threshold can vary based on age and other factors.
- Implications: A normal PSA, TOTAL suggests that the overall level of PSA in the blood is within expected limits for a man without significant prostate disease.
Low PSA, % FREE:
- Definition: PSA, % FREE is the ratio of free (unbound) PSA to total PSA. A low PSA, % FREE typically means that less than 25% of the total PSA is in the unbound form.
- Implications: A low PSA, % FREE can indicate a higher likelihood of prostate cancer. Specifically, a % FREE PSA below 10% is associated with a significantly increased risk, whereas levels between 10-25% suggest a moderate risk.
Combined Interpretation;
Normal PSA, TOTAL with Low PSA, % FREE:
- Diagnostic Considerations: This combination can be puzzling because a normal total PSA might suggest that there is no significant prostate issue, yet a low % FREE PSA raises concern for prostate cancer.
- Potential Scenarios: This scenario might occur in the early stages of prostate cancer where the total PSA has not risen significantly but the proportion of free PSA is lower due to increased production of bound PSA by cancer cells.-
- Clinical Actions: Given this potentially conflicting information, healthcare providers may consider further evaluation despite the normal total PSA. This could include:
→ Repeat PSA Testing: Monitoring PSA levels over time to see if there is an upward trend.
→ Digital Rectal Exam (DRE): Physical examination to check for abnormalities in the prostate.
→ Imaging Studies: Such as transrectal ultrasound or MRI to get a clearer picture of the prostate.
→ Biopsy: If there is significant concern based on % FREE PSA and other risk factors, a prostate biopsy may be recommended to directly assess for the presence of cancer cells.
Importance of Context:
- Individual Risk Factors: Age, family history, race, and previous PSA levels all play a role in interpreting these results.
- Symptoms: Any symptoms such as difficulty urinating, pelvic pain, or blood in the urine or semen would also guide the next steps.
In summary, a normal PSA, TOTAL with a low PSA, % FREE should prompt careful consideration and possibly further investigation to rule out or confirm the presence of prostate cancer, even if the total PSA is within the normal range.
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FREE PSA RISK ASSESSMENT
The probability of prostate cancer for men with non-suspicious DRE results, categorized by age group and using PSA values between 4.000 and 10.000 ng/mL and percent FREE PSA values, is summarized in the table below:
Probability of Cancer*
| % Free PSA | 50-59 years | 60-69 years | ≥70 years |
|---|---|---|---|
| ≤10 | 49.2% | 57.5% | 64.5% |
| 11-18 | 26.9% | 33.9% | 40.8% |
| 19-25 | 18.3% | 23.9% | 29.7% |
| >25 | 9.1% | 12.2% | 15.8% |
*Probability of finding prostate cancer by needle biopsy.
Note: Calculation of percent FREE PSA may not be possible when the value for TOTAL PSA is in the low normal range. These guidelines are based on assays performed using the Roche E602 immunoassay system (8/2015; V8.0).
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I have been using Healthmatters.io since 2021. I travel all over the world and use different doctors and health facilities. This site has allowed me to consolidate all my various test results over 14 years in one place. And every doctor that I show this to has been impressed. Because with any health professional I talk to, I can pull up historical results in seconds. It is invaluable. Even going back to the same doctor, they usually do not have the historical results from their facility in a graph format. That has been very helpful.
Karin
Advanced Plan Member since 2020
What fantastic service and great, easy-to-follow layouts! I love your website; it makes it so helpful to see patterns in my health data. It's truly a pleasure to use. I only wish the NHS was as organized and quick as Healthmatters.io. You've set a new standard for health tracking!
Paul
Healthmatters Pro Member since 2024
As a PRO member and medical practitioner, Healthmatters.io has been an invaluable tool for tracking my clients' data. The layout is intuitive, making it easy to monitor trends and spot patterns over time. The ability to customize reports and charts helps me present information clearly to my clients, improving communication and outcomes. It's streamlined my workflow, saving me time and providing insights at a glance. Highly recommended for any practitioner looking for a comprehensive and user-friendly solution to track patient labs!
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Alpha Fetoprotein (AFP), CA 125, CA 15-3, CA 19-9, CA 27.29, CA 72-4, Carcinoembryonic Antigen (CEA), CD19, Chromogranin A (CgA), CYFRA 21-1 (Cytokeratin 19 Fragment), Leukemia/Lymphoma/Myeloma Panel by Flow Cytometry, Matrix Metalloproteinase 9 (MMP 9), MMP-9 (Matrix Metalloproteinase-9), Neuron-specific Enolase (NSE), Neurone Specific Enolase, PapIG, HPV, rfx 16/18, Prostate Cancer Risk Score, Prostate Specific Antigen (PSA), PSA, % Free, S100, Squamous Cell Carcinoma, Total Prostate Specific Antigen (TPSA), Tumor Necrosis Factor-Alpha, Highly Sensitive, Urinary Bladder Cancer Antigen
