PSA revolutionized the screening and management of prostate diseases. It is currently the most widely used cancer marker – but scientists warn it also may be a dangerously overused one. High levels can point to prostate cancer or other, non-cancerous prostate problems. Read on to learn more about the PSA test.
What is the Prostate-Specific Antigen (PSA)?
Definition
Prostate-specific antigen (PSA) is a protein that is made in the prostate. An antigen is a signal for the immune system to mount an attack. It can be foreign to the body – such as from a toxin or bacteria – or created by the body, such as PSA [1].
Both healthy and cancerous cells make PSA, though cancerous prostate cells may produce it in higher amounts. Thus, the PSA test is used to screen for prostate cancer [1].
PSA can also rise due to other non-cancerous conditions such as prostate inflammation, benign prostate enlargement, and urinary tract infection [1].
PSA Blood Test
Prostate Cancer Screening
PSA tests are mainly used to screen for prostate cancer.
Many factors can influence PSA levels. The PSA blood test is not specific enough to diagnose prostate cancer and it may give false-negative results.
Additionally, PSA levels increase with age. Levels can also be high if you have an enlarged prostate (benign prostatic hyperplasia) or prostate inflammation (prostatitis) [2, 3, 4].
Doctors usually order the test when a man is showing prostate cancer symptoms, such as [5]:
- Frequent urination
- Painful urination
- Back pain
- Pelvic pain
Because of the high chance of false positive results, men over 55 should decide whether to undergo periodic PSA-based screening after discussing potential benefits and harms of screening on the basis of family history, race/ethnicity, medical conditions, etc. with their doctor. This test is not recommended for men over 70 [6].
Procedure
A healthcare professional will take a blood sample from a vein in your arm, which will be sent to a laboratory for analysis. The results are typically reported as nanograms of PSA per milliliter (ng/mL) of blood.
Refrain from exercising or performing any activity that causes pressure (e.g. riding a bike) on your prostate before your blood test. You should also refrain from ejaculating for 24 hours before the test [7, 8].
Your doctor may also order additional tests to screen for or monitor prostate cancer such as a kallikrein panel (4k-panel) and prostate cancer antigen 3 (PCA3). They may also perform a transrectal ultrasound and a digital rectal examination [9, 10].
PSA Screening Drawbacks & Considerations
The Controversy
The thought of diagnosing cancer by running a blood test was unimaginable until recently. The discovery of PSA was big news, giving doctors and patients hope that early, non-invasive screening and diagnosis might be possible [11].
However, the discovery of PSA was controversial from the start. Many scientists have been researching PSA independently since the 60s. They found it both in the prostate and in the semen, and they all gave it different names. Some even considered PSA in the semen a useful forensic marker for rape victims [11].
Several scientists came to realize PSA’s potential for prostate cancer screening. Still, only one scientist took the fame for its discovery, while the others were unfairly discredited [11].
The controversy doesn’t end there. PSA quickly became the most widely used marker in the diagnosis and follow‐up of cancer. But in truth, PSA lacks the qualities of an ideal tumor marker [11].
When Should You Test Your Levels?
Up until recently, professional organizations recommended yearly PSA screening for all men once they turn 40. Some advocated even earlier screening for high-risk populations, such as African Americans or men who have a family history of prostate cancer [4].
However, recent findings turned the guidelines around. Studies revealed that some men with normal PSA levels (below 4.0 ng/mL) have prostate cancer, while many men with higher levels do not [12].
New reports indicate that the widespread use of PSA tests led to prostate cancer overdiagnosis in the United States. In turn, many professional associations revised their guidelines, turning against routine screening in most cases – and especially in men under 55 or over 70 years old [6, 13].
The overall benefit of PSA screening for prostate cancer in men aged 55 to 69 years is small. Ultimately, men in this age group have to decide whether they want to have the PSA test done or not, even if they belong to a high-risk group [6].
To decide whether to have a PSA test, discuss the issue with your doctor, considering your risk factors and weighing your personal preferences. We will now discuss some of the limitations of this test.
PSA Test Limitations
Marginal Benefit from Knowing You Have Prostate Cancer
The PSA test can detect small tumors that may be harmless. It may also give false positives, which leads to overtreatment [6].
Even if you have prostate cancer, there is no guarantee that you have an increased risk of dying from it. Most types of prostate cancer grow slowly and don’t cause any symptoms. About a third of older men die from other causes never even knowing they had prostate cancer [6].
You May Receive Treatment You Don’t Need and Experience Side Effects
Some physicians believe that overtreatment and the psychological stress of getting a cancer diagnosis may be more damaging to your health than most forms of prostate cancer [6].
Common side effects of prostate cancer treatment include erectile dysfunction, urinary incontinence, and bowel problems [6].
The harms of screening in men older than 70 years are even higher, since older men are more likely to get a false positive, suffer health complications from biopsies, and experience more serious treatment side effects [6].
You May Get a False Negative
A PSA test can also give a false negative, indicating that you don’t have cancer when the opposite is true. That’s because some men with prostate cancer have low PSA [12].
Making a Decision
PSA screening in men aged 55 to 69 years may prevent approximately 1 death from prostate cancer per 1000 men screened, over about 13 years. That’s considered a small benefit, and if you fall within this age range you should discuss the merits of this test with your physician [6].
PSA Levels & Test Results
Test Types and Results
Several types of PSA tests exist.
- Total PSA, which measures the total amount of prostate-specific antigen in your blood
- Free PSA, which measures the amount of free prostate-specific antigen in your blood
- PSA Free/Total ratio (percent free PSA), which measures the ratio of free to total ratio prostate-specific antigen in your blood
Prostate tumors normally produce bound PSA, while harmless (benign) prostate cells produce free PSA. Free PSA tests are only used to find the free/total PSA ratio. A high ratio indicates that most of your PSA are in the free form and that you do not have prostate cancer [14, 15, 16].
However, free/total PSA ratio is not accurate enough to determine whether you have prostate cancer. It should be combined with other markers and exams [17, 16].
On the other hand, having low free PSA levels and high total PSA levels are associated with:
- A higher risk of prostate cancer [18]
- Increased tumor size [19]
- Progression of prostate cancer to a more aggressive form [20]
- Dying from prostate cancer [21]
Have in mind that ejaculation within 24 hours of a PSA test will result in falsely high results and/or a low free/total PSA ratio [8].
Normal PSA Levels by Age
For total PSA, the following values are considered normal [22, 23]
- 0-2.5 ng/mL for men aged 40-49 years
- 0-3.5 ng/mL for men aged 50- 65 years
- 0.0-4.5 ng/mL for men aged 60-69 years
- 0.0-6.5 ng/mL for men aged 70-79 years,
In women, total PSA should be under 0.002 ng/mL [24]
Free PSA in the range of 0.2 to 5.0 ng/mL is normal in men with total PSA levels of 4.0-10.0 ng/mL. The following levels are considered normal by age in healthy men [18, 25]:
- 0.5 ng/mL for men 40-49 years old
- 0.7 ng/mL for men 50-59 years old
- 1.0 ng/mL for men 60-69 years old
- 1.2 ng/mL for men 70-79 years old
The PSA Free/Total index should be >25% [18]
If Your Results Are Normal
For men, normal results – most importantly a normal free/total PSA ratio should mean that the prostate is healthy. However, that’s not always the case [2, 26].
However, it’s important to remember that a normal PSA and PSA free/total ratio doesn’t mean a condition such as prostate cancer is absent. Your doctor will interpret your results, taking into account your medical history, symptoms, and other test results.
In addition, falsely low PSA levels may be caused by certain medications or unhealthy habits such as:
- Obesity and being overweight [27]
- Heavy alcohol drinking [28]
- NSAIDs, anti-inflammatory drugs including aspirin [29, 30]
- Acetaminophen, a pain reliever and fever reducer (paracetamol, Tylenol, Panadol) [30]
These can all interfere with your PSA measurement.
Elevated PSA
Causes
Causes shown here are commonly associated with higher PSA. Work with your doctor or another health care professional to get an accurate diagnosis. Your doctor will interpret this test, taking into account your medical history, signs and symptoms, and other test results.
The most common cause of high total PSA levels in men is prostate cancer [31, 7].
Other possible causes of high PSA in men include [7, 32]:
- Exercise, especially biking [33]
- Higher fat intake compared to protein intake [32]
- Recent ejaculation (within 24 hours) [34]
- Pressure on the prostate (rectal examination, biopsy, etc.) [7]
- Urinary tract infection [35]
- Prostate inflammation (prostatitis) [36]
- Enlarged prostate (benign prostatic hyperplasia) [37]
In women, high total PSA levels be caused by:
- Pregnancy [38]
- High androgen levels [39]
- Non-cancerous breast tumors (fibroadenomas) and cysts [40]
- Cancer of the female prostate gland (Skene’s gland) [41]
If you have no symptoms of prostate cancer and your PSA test results came back high, your doctor may repeat the test and recommend regular check-ups to monitor your levels.
If your PSA levels are rapidly rising or your doctor finds a lump during a digital rectal exam, he or she may run additional tests and recommend a prostate biopsy if prostate cancer is suspected.
Addressing Elevated PSA
The most important thing is to work with your doctor to find out what’s causing your high PSA levels and to treat any underlying conditions.
Discuss the additional lifestyle changes listed below with your doctor. None of these strategies should ever be done in place of what your doctor recommends or prescribes!
A study suggests that eating a diet that contains more polyphenol-rich foods, such as pomegranate, green tea, broccoli, and turmeric, may be beneficial in those with prostate cancer [42].
Another study has found a link between lower folate, which is basically a measure of fresh fruit and vegetable intake, and prostate cancer. Higher intake of fruits and veggies may be beneficial for preventing prostate cancer [43].
Talk to your doctor about the following foods and supplements. Initial studies suggest they may be beneficial for prostate health:
- Soluble fiber (in healthy men) [44]
- Garlic (in healthy people) [45, 46]
- Sulforaphane (in people with prostate cancer) [47, 48]
- Lycopene (in healthy people and those with prostate cancer) [49, 50]
- Genistein (soy) (in healthy people and those with prostate cancer) [51, 50]
- EGCG (in people with prostate cancer) [52]
Remember, always speak to your doctor before taking any supplements, because they may interfere with your health condition or your treatment/medications!
Takeaway
Prostate specific antigen (PSA) is a protein made in the prostate. PSA tests are widely used to screen for prostate cancer. In fact, they were used so much after the initial hype that prostate cancer started to be overdiagnosed. Many people who didn’t have prostate cancer received treatment and suffered side effects. Others went through the stress of getting a cancer diagnosis. New guidelines state that the harms of routine PSA testing might outweigh the benefits in most cases. There’s a small benefit of testing for men between 55 to 69 years old. If you fall within this range, do your research and discuss the PSA test with your doctor. PSA tests require a blood sample and can measure free PSA, total PSA, or their ratio. If your levels are high, your doctor may need to repeat the test or run additional tests and exams.
