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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Total PSA levels can vary slightly, but general normal ranges (in nanograms per milliliter, ng/mL) are as follows:
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
A PSA level above the expected range may indicate an increased risk of prostate cancer. However, this is not conclusive proof of cancer. Doctors will compare total PSA results with those of the free PSA test for a more accurate assessment. It's important to note that different medical organizations may have slightly varying guidelines for what constitutes a normal PSA level.
The free PSA ratio provides additional insights:
Higher Ratio: A higher ratio of free PSA to total PSA is generally a sign of better prostate health.
Lower Ratio: A low free PSA level (under 25%) in combination with a high total PSA level increases the likelihood of prostate cancer.
If the free-to-total PSA ratio is:
0-10%: The risk of cancer can be as high as 56%.
Above 25%: The risk of cancer drops to around 8%.
While these ratios provide useful information, they are not definitive proof of cancer, and further tests, such as a biopsy, may be necessary.
Doctors will consider other factors like:
Age, Ethnicity, and Prostate Size: PSA levels tend to rise with age and can be influenced by ethnicity and prostate size.
PSA Kinetics: This involves how PSA levels change over time, which may be crucial in evaluating cancer progression or recurrence. Key aspects of PSA kinetics include:
PSA Velocity: Measures how quickly PSA levels rise, potentially indicating a recurrence of prostate cancer.
Doubling Time: The time it takes for PSA levels to double. A faster doubling time may suggest a more aggressive form of cancer.
Elevated PSA levels can also result from non-cancerous conditions such as prostatitis (inflammation of the prostate) or benign prostatic hyperplasia (BPH). These conditions are common and should be considered when interpreting PSA results.
When PSA, TOTAL is within the normal range, but % Free PSA is low, it can present a complex situation. Here’s an explanation of each result:
Normal PSA, TOTAL: Typically, a PSA level below 4.0 ng/mL is considered normal, although this threshold can vary based on age and other factors. A normal total PSA suggests there is no significant prostate disease.
Low PSA, % Free: The % Free PSA is the ratio of free (unbound) PSA to total PSA. A low % Free PSA (especially below 10%) is associated with a higher risk of prostate cancer. Levels between 10-25% indicate moderate risk.
This combination can be puzzling because the normal total PSA suggests no significant prostate issue, while a low % Free PSA raises concern about the possibility of prostate cancer.
Early Stage Cancer: In the early stages of prostate cancer, the total PSA may not rise significantly, but the proportion of free PSA decreases due to increased production of bound PSA by cancer cells.
Repeat PSA Testing: To monitor for trends or rising PSA levels over time.
Digital Rectal Exam (DRE): A physical exam to check for abnormalities in the prostate.
Imaging Studies: Such as a transrectal ultrasound or MRI to assess the prostate more clearly.
Biopsy: If there is significant concern based on the % Free PSA and other risk factors, a prostate biopsy may be recommended.
Risk Factors: Age, family history, race, and previous PSA levels influence how results should be interpreted.
Symptoms: Symptoms such as difficulty urinating, pelvic pain, or blood in the urine or semen may suggest the need for further evaluation.
While PSA testing is a valuable tool for screening, it has limitations. It cannot distinguish between aggressive and indolent cancers, and there is a risk of false positives and negatives. Therefore, it is crucial to consider PSA results in the context of other diagnostic tools and clinical judgment.
For men with non-suspicious DRE results, using PSA values between 4.000 and 10.000 ng/mL and % Free PSA values, the probability of prostate cancer (based on biopsy results) varies by age group:
| % 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% |
Note: Calculation of % Free PSA may not be possible if the total PSA value 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
