PSA level: What does it mean, and when is it too high?

What is the PSA level and what does it indicate?

PSA stands for prostate-specific antigen. It is a protein produced by cells in the prostate and is found primarily in seminal fluid. Small amounts also enter the bloodstream, where they can be measured by a blood test. The PSA level can provide an indication of whether the prostate has changed. However, it is not a specific cancer marker. Benign changes, such as an enlarged prostate or inflammation, can also cause the PSA level to rise. Conversely, a low PSA level does not definitively rule out prostate cancer. The level is therefore assessed in conjunction with other findings and individual risk factors.

What PSA level is still considered normal?

There is no fixed PSA threshold above which prostate cancer is definitely present. Even a low level does not completely rule out prostate cancer. Conversely, an elevated level may have benign causes, such as an enlarged prostate or inflammation.

For early detection, the German S3 guideline recommends that a PSA level of 3 ng/ml or higher should be re-measured within three months, taking into account any factors that may influence the result. If it remains elevated, a urological assessment should be carried out. For lower levels, the follow-up interval depends on the baseline value and the individual’s risk.

Laboratory reports often state 4 ng/ml as the reference limit. This serves as a guide in the laboratory report. For early detection, however, a follow-up test is recommended from as low as 3 ng/ml. A value below the stated laboratory limit therefore does not automatically mean that no further monitoring is required.

PSA levels at a glance

For men aged 45 and over, it is recommended that screening intervals be determined based on the first PSA result measured. The following table applies to early detection, not to follow-up care for men who have already been diagnosed with prostate cancer.

This classification is used to determine the next course of action. Elevated levels do not constitute a diagnosis of cancer. If you have symptoms or specific risk factors, a different approach may be necessary.

If a close relative, such as a father or brother, has had prostate cancer, this should be discussed during the consultation. PSA-based screening is also recommended from the age of 45 in cases of a family history of the condition. In the case of certain hereditary genetic mutations, such as in the BRCA2, MSH2 or MSH6 genes, specialist risk counselling may be advisable from the age of 40.

Does age play a role in PSA levels?

On average, PSA levels rise with age, partly because the prostate often grows larger. For this reason, age-adjusted reference values are sometimes used. 

However, age alone is not sufficient for risk assessment. The size of the prostate, other risk factors and the trend in PSA levels are also taken into account. An elevated PSA level should therefore not be attributed solely to age and classified as harmless.

What are the possible causes of an elevated PSA level?

An elevated PSA level can have many causes. Prostate cancer is just one of them. As the prostate-specific antigen is produced by prostate cells, the level can generally rise in response to various changes or irritations affecting the prostate. 

Common causes include:

• benign prostatic hyperplasia (BPH): The prostate often enlarges with age. This can cause more PSA to enter the bloodstream.
• Inflammation of the prostate (prostatitis): Inflammation can significantly increase the PSA level.
• Urinary tract infections: Feverish infections in particular can lead to sharply elevated PSA levels.
• Acute urinary retention: If the bladder suddenly cannot be emptied, the PSA level may rise temporarily.
• Prostate procedures: A prostate biopsy, in particular, can cause a temporary rise in the level.
• Prostate cancer: A malignant tumour of the prostate can also lead to an elevated PSA level.

In addition, ejaculation can have a short-term effect on the PSA level. Whether cycling causes a significant increase in the level, however, is not clearly established. Such potential factors should be taken into account before a follow-up test.

How is the PSA level determined?

The PSA level is determined by a blood test. The concentration of prostate-specific antigen in the blood is measured; the result is usually given in nanograms per millilitre (ng/ml). 

Total PSA is particularly relevant for the assessment. In certain situations, free PSA in the blood is also measured and the PSA ratio is calculated from this. These values can help to interpret an abnormal total PSA level more accurately.

What are the advantages and disadvantages of the PSA test for early detection?

PSA screening can help to detect and treat prostate cancer at an early stage. It can reduce the risk of metastases forming unnoticed and, as a result, of a man dying from prostate cancer. It is also often possible to use a less invasive treatment if the tumour is detected early. However, not all men benefit from this.

An elevated PSA level can trigger further investigations even when no cancer is present. This can be unsettling. Early detection can reveal tumours that would never have caused any symptoms during a man’s lifetime. This is known as overdiagnosis. If such tumours are unnecessarily treated with surgery or radiotherapy, those affected may suffer side effects such as incontinence or erectile dysfunction without benefiting from the treatment. This is referred to as overtreatment. 

Whether the benefits or the drawbacks outweigh each other is a personal decision. A consultation with a doctor helps to take into account one’s own risk, state of health and personal wishes.

How do you prepare for a PSA test?

To ensure results that are comparable, the blood sample should be taken under similar conditions wherever possible. The European Association of Urology (EAU) specifically recommends avoiding or taking into account potential factors such as ejaculation, prostate procedures and urinary tract infections.

Before the PSA test, it is therefore advisable to:

• Avoid ejaculation: To ensure the results are as comparable as possible, it is often recommended to refrain from ejaculation for 48 hours prior to the blood test.
• Report any infections: Urinary tract infections and prostatitis can significantly increase PSA levels. A test for early cancer detection should generally only be carried out once the acute infection has subsided. The treating doctor will determine the appropriate time.
• Report any recent procedures: You should wait at least one month after a prostate biopsy before having a PSA test. 
• List any medication: Active ingredients such as finasteride or dutasteride can significantly lower the PSA level and must be taken into account when interpreting the results. 
• Use the same laboratory wherever possible for follow-up tests: Different measurement methods can lead to slightly different results. 
• Take note of advice regarding cycling: If your levels are borderline or elevated, it may be advisable to avoid long or strenuous cycle rides before a follow-up test. No generally applicable waiting period can be derived from the available studies.

You do not usually need to fast before a PSA test. The key factors are those that can influence the PSA level itself.

What happens if the PSA level is elevated?

An elevated PSA level does not automatically mean that prostate cancer is present. The first step is to check whether temporary factors such as inflammation, a urinary tract infection, ejaculation or a recent surgical procedure might have affected the result.

As part of early detection, a level of 3 ng/ml or above is initially monitored over a three-month period. If it remains elevated, a urological assessment follows. This does not mean that one should always wait three months: the timing depends on the findings and any symptoms. If an increased risk of prostate cancer is confirmed, an MRI scan of the prostate is usually carried out. This helps to identify suspicious changes and determine whether a tissue sample is necessary. Consequently, a biopsy is not automatically performed today following a single elevated PSA level. 

For further risk assessment, additional factors such as PSA density, age, family history, digital rectal examination findings and MRI results may be taken into account. If the MRI is normal and the overall risk is low, a biopsy may, under certain circumstances, be deferred initially whilst the PSA level is monitored further.

What do free PSA, PSA ratio and PSA density mean?

In addition to total PSA, other PSA values can help to assess an abnormal finding more accurately. They provide additional information but, on their own, can neither confirm nor rule out prostate cancer.

• Free PSA: In the blood, PSA is present partly in a free form and partly bound to proteins. In benign conditions, the proportion of free PSA is often higher than in prostate cancer.
• PSA ratio: This describes the ratio of free PSA to total PSA and is usually expressed as a percentage. A lower proportion of free PSA may be associated with a higher risk of prostate cancer. However, there is no universally applicable threshold value that can be used to definitively detect cancer. 
• PSA density: This involves comparing the PSA level to the size of the prostate. A large, benignly enlarged prostate, for example, may produce more PSA without there being any cancer present. A higher PSA density, on the other hand, may indicate an increased risk. The prostate volume is determined using MRI or ultrasound.

PSA density, in particular, is used in conjunction with the MRI findings to decide on the next course of action.

What is the significance of the PSA level in prostate cancer?

The PSA level plays an important role in several stages of prostate cancer: in early detection and diagnosis, but also in monitoring progress following treatment. Different criteria apply here than in early detection. Following treatment, the PSA level is monitored regularly. The trend over time is particularly important here. Following complete surgical removal of the prostate, the PSA level should fall to a level that is no longer detectable.

A renewed rise in the PSA level following treatment may indicate what is known as a biochemical recurrence. In such cases, the rising PSA level can provide evidence of tumours returning before they can be detected by other tests.  The current S3 guideline defines a biochemical recurrence as a situation where, following complete surgical removal of the prostate, the PSA level is above 0.2 ng/ml in at least two measurements.

Following radiotherapy, the PSA level is assessed differently, as prostate tissue is preserved. In this case, a rise of 2 ng/ml above the lowest PSA level achieved after treatment is considered a biochemical recurrence. Here, too, a single measurement is not sufficient; the trend over time is decisive.

In the event of a rise, the PSA doubling time, the time since the original treatment and other tumour characteristics can also help to assess the likelihood of a local or systemic recurrence.

How often should PSA levels be monitored?

How often the PSA level should be monitored depends primarily on the baseline value and individual risk. The table above lists the recommended monitoring intervals for early detection. If symptoms are present, additional risk factors exist or abnormal findings are noted, a different approach may be required.

Multiple measurements can help to distinguish between temporary fluctuations and persistent changes. An abnormal result should, where possible, be reassessed under comparable conditions. The key factor remains a joint assessment alongside other findings. Different screening intervals apply following prostate cancer treatment. These are based on the treatment, tumour risk and the course of the disease to date, and are determined on an individual basis.