Prostate-specific antigen (PSA) is a blood test secreted by the prostate and widely used in the diagnosis of prostate cancer. It was first measured in blood in 1980. Today, it is an important tumor marker used in the diagnosis and follow-up of prostate cancer. In this article, I will give general information about PSA.

What is prostate specific antigen (PSA)?

PSA is a glycoprotein secreted from epithelial cells in the prostate. PSA has a molecular weight of 34 000 daltons and a half-life of 3.15 days. PSA is produced not only by cancer cells, but also by both cancerous and normal cells. It was started to be used in the follow-up of the disease in patients with prostate cancer in the USA in 1986. It has been widely used in the diagnosis and follow-up of prostate diseases, especially prostate cancer, since the 1980s.

PSA is normally found in higher levels in the seminal fluid (semen) than in the blood and is responsible for the soft consistency of the seminal fluid (liquefaction). Thanks to a protective layer called the blood prostate barrier, a small amount passes into the blood. In cases where the blood prostate barrier is disrupted (such as prostate cancer), PSA is mixed into the blood in higher amounts.

Why is the PSA test done?

The PSA test is used to differentiate benign prostate enlargement from prostate cancer. Apart from this, other areas where the PSA test is used in the clinic are;

• In the diagnosis of prostate cancer
• Used as a screening test in prostate cancer screening
• In evaluation of response to treatment
• In the follow-up of the recurrence of the disease

What are the derivatives of PSA?

There are some subgroups (derivatives) of PSA. Each of these has different uses. Frequently used PSA derivatives are;

• Total PSA: It is one of the first tests to be checked in the blood of those with suspected prostate cancer.
• Bound PSA: 65-95% of PSA protein, which is secreted from prostate epithelial cells and passed into the blood, is bound to proteins. PSA is mostly bound to two proteins called alpha 1-anichymotrypsin (ACT) and alpha2-macroglobulin (A2M).
• Free PSA (fPSA): As low as 5-35% of circulating PSA levels are found free without binding to any protein. Free PSA in this way is known as “free PSA”.
• Free PSA/total PSA ratio: f PSA levels decrease in patients with prostate cancer. If the %f PSA rate is 10%, it means 56% of these patients, and if it is 25%, 8% of the patients have prostate cancer detection rate.
• PSA density: It is calculated by dividing the blood PSA level by the prostate volume. As the prostate weight increases, PSA production also increases and the PSA level in the blood is high. In these cases, prostate density is checked to differentiate prostate cancer from benign prostate enlargement (PSA). If PSA level between 4-10 ng/ml and PSA density is 0.08 ng/ml – 0.15 ng/ml  prostate biopsy should be done.
• Pro -PSA: Pro PSA refers to inactive forms of PSA. It is a more important test in detecting prostate cancer.
• Prostate Health Index (PHI): It is used to estimate the rate of prostate cancer as a result of biopsy in patients with PSA values ​​of 4-10 ng/ml and no evidence of cancer on examination. Three different PSA markers (PSA, free PSA, and p2PSA) are used to calculate PHI.
• PSA velocity: PSA normally increases at an average of 0.05 ng/ml per year. This increase is higher in cancer patients.
• PSA doubling time: It expresses the doubling of PSA level in a certain time. This period is shorter in rapidly progressing cancers.
• PSA density: PSA is secreted from both normal prostate and cancerous prostate. PS is performed at a higher rate in prostate cancer than in normal prostate. PSA density reflects the amount of PSA made depending on the size of the prostate.
• 4Kcsore test: Here, 4 different forms of PSA are examined: total PSA, free PSA, intact PSA and human kallikrein 2.
• Urine markers: PCA3 (prostate cancer antigen 3) m RNA and TMRSS2-ERG gene fusion are tests in the urine for the diagnosis of prostate cancer.

How is the PSA test done?

PSA is measured in blood drawn from a test arm vein. For this, hunger or satiety is not important. PSA test can be done by taking blood from the patient at any time of the day.

What should normal PSA values ​​be?

It is difficult to say the normal values ​​of PSA. It has no net worth. Its elevation indicates prostate cancer. Classically, if the PSA is above 4.0 ng/ml, it was thought that the probability of prostate cancer is high and biopsy should be taken. Considering the fact that there is prostate cancer in the family, the age and race of the patient, it should be careful because prostate cancer may be below this level. It is not correct to evaluate patients based on PSA values ​​alone. We take a detailed anamnesis from our patients and also make a digital prostate examination.

PSA values ​​by age

PSA values ​​increase with age. The fact that PSA measurements are within these values ​​does not mean that there is no cancer. A prostate examination should also be done. PSA values ​​according to certain age ranges are as follows;

• 0-2.5 ng/ml between the ages of 40-49
• 0-3.5 ng/ml between 50-59 years old
• 0-4.5 ng/ml between the ages of 60-69
• 70 years and older 0-6.5 ng/ml

What should be considered before having a PSA test?

Although there is no cancer, PSA values ​​may also be high in normal people. For this reason, the following points should be considered before performing the PSA test;

• Cycling, horse riding
• Cycytoscopic interventions
• Prostate massage
• It should be taken at least 48 hours after sexual intercourse
• Should be taken at least 48 hours after a heavy exercise
• If there is a urinary infection, it should be taken after treatment.
• If prostate biopsy is done, it should be taken 6 weeks later.

What are the advantages of the PSA test?

PSA testing has some advantages in patients with prostate cancer. These:

• It enables prostate cancer to be detected at an earlier stage
• It is used in the follow-up of prostate cancer treatment
• Helps to follow up on recurrences

When to have a PSA test?

Men of all ages do not need a PSA test. The American Cancer Society and the American Urological Association recommend some criteria for PSA screening.

• There is no need for prostate cancer screening under the age of 40.
• If the risk of cancer is high, it is checked between the ages of 40-45.
• If there is a moderately high risk of prostate cancer, it is examined in patients aged 50 years.
• If there is a high risk of cancer in men between the ages of 40-54, screening should be done.
• Between 55-69 years old, if the urologist deems it necessary, screening is done
• There is no need for screening in men aged 70 years or older or who are not expected to have a life expectancy of 10-15 years.
• PSA test should be done in those aged 55-69 years who are at risk of prostate cancer.

Drugs that lower PSA

PSA, an important tumor marker in prostate cancer, is affected by some drugs. Patients for whom PSA measurement is requested should be asked whether they use these drugs. Drugs that lower blood PSA levels include:

• 5-alpha reductase inhibitors: Finasteride (Proscar) (5-alpha-reductase) and Dutasteride (Avodart)
• Herbal medicines: Taking some herbal supplements for support can lower the PSA level.
• Some other drugs: Long-term aspirin, statins (cholesterol lowering drugs), thiazide diuretics can lower PSA.

Do drugs used for benign prostate enlargement lower PSA?

The most commonly used drugs in the treatment of benign prostate enlargement (BPH) are alpha blocker group drugs. These drugs have no effect on prostate size and PSA, and do not reduce PSA values. The 5-alpha reductase inhibitors Finasteride (Proscar) and Dutasteride (Avodart), which are used in the treatment of BPH, shrink the prostate because they reduce testosterone and decrease PSA values.

What to do if PSA is high?

If the PSA is high in the blood test, it does not necessarily mean that you have prostate cancer. Other causes that increase the PSA level should also be investigated. In patients with high PSA, prostate examination should be performed, multi-parametric prostate MRI (MP-MR) should be requested and a biopsy should be taken according to the result. In summary, the path to be followed in patients with high PSA;

• Rectal examination
• MP-MR
• Biopsy

Who is at higher risk of prostate cancer?

The incidence of prostate cancer increases with age. Not every patient has the same risk of developing prostate cancer. People at high risk of prostate cancer include:

• Those with a family history of prostate cancer
• Higher in black race
• The risk is higher in obese
• Men aged 50 and over
• If there are some genetic changes that increase susceptibility to prostate cancer

Does high PSA indicate definite cancer?

High PSA increases the chance of cancer, but not every high level means cancer. We can summarize the probability of having prostate cancer according to PSA levels as follows.

• If PSA is below 4 ng/mL: 15% chance of having prostate cancer
• If PSA is between 4-10 ng/mL: 25% chance of having prostate cancer
• If PSA is 10 ng/mL and above: My chance of having prostate cancer is over 50%

What are the causes that increase PSA?

When evaluating the PSA test, patients should be questioned in detail. Diseases or conditions that increase PSA values ​​other than prostate cancer are as follows;

• Prostatitis (prostate inflammation)
• Too large prostate volume
• •Urinary tract infection
• Advanced age
• Insertion of a urethral catheter
• Urethroscopy/cystoscopy
• Ejaculation (sexual intercourse)
• Prostate massage
• Prostate biopsy
• Some drugs (testosterone intake)
• Urinary retention (globe vesica, inability to urinate)
• Long-term cycling

How can it be understood that the high PSA level is due to prostatitis or cancer?

It is not possible to understand that PSA elevation is due to prostatitis (prostate inflammation) or prostate cancer, only with PSA values. If PSA is high, a urological examination of the patient, investigation of prostate cancer risk, and multiparametric prostate MRI should be performed. If prostate cancer is suspected as a result of MRI, it is possible to make a definitive diagnosis by taking a prostate biopsy.

How should prostate biopsy be performed in patients with high PSA?

Definitive diagnosis is made by biopsy in patients with elevated PSA. It is clearly demonstrated by biopsy that the height is due to cancer or prostatitis. Prostate biopsy was formerly performed with transrectal ultrasonography. Today, it is performed with the “fusion biopsy” method. Since biopsy is taken directly from the suspicious area in fusion biopsy, the rate of cancer detection is very high.

Is there any sign of high PSA?

PSA elevation does not have any specific symptoms. But patients with a high PSA result often have prostate-related disorders.

When should PSA be checked regularly?

PSA is an important cancer marker used both in the diagnosis of prostate cancer and in the follow-up of its treatment. Serum PSA levels should be checked at regular intervals in the following cases;

• Patients previously diagnosed with prostate cancer and under active observation
• Patients who underwent surgery for prostate cancer
• Patients receiving radiotherapy for prostate cancer
• Patients receiving drug therapy/chemotherapy
• Patients over 50 years of age receiving testosterone therapy

Prostate cancer risk classification according to PSA level

Blood PSA measurements are also used for risk assessment in patients with prostate cancer. It is possible to divide cancer into three risk groups according to PSA values, grade (Gleason grade) and stage of prostate cancer;

• Low-risk prostate cancer: PSA < 10, Gleason score ≤ 6, and stage ≤ T2arostat
• High-risk prostate cancer: PSA 10-20, Gleason score 7, or stage T2b/c
• High-risk prostate cancer: PSA > 20, Gleason score ≥ 8, or stage ≥ T3

How often should the PSA test be done?

In men who do not have prostate cancer, PSA measurement is made at very frequent intervals unnecessarily. However, it is not very accurate to do this test at frequent intervals. According to the results of the PSA test, the measurement is repeated in the patients. Men with a PSA level of 2.5 ng/ml and below should have a PSA measurement every 2 years, and those with a PSA level of 2.5 ng/ml and above once a year.

Does the use of antibiotics lower the PSA level?

One of the causes of high PSA is prostate infection (prostatitis). PSA levels decrease with the use of appropriate antibiotics effective against prostatitis for more than 2 weeks. However, it is not correct to start antibiotics for every patient with high PSA. A urologist should definitely evaluate the patient. Trying to reduce PSA with antibiotic treatment, if the patient has prostate cancer, delays the diagnosis of cancer and causes the patient to lose time and progress the disease.

How is PSA elevation treated?

PSA elevation is not a disease. If PSA is high, certain diseases should be considered, especially prostate cancer. Patients with high PSA values ​​should be evaluated by a urologist, prostate examination should be performed, and effective treatment for the disease should be planned after the necessary examinations are made and the cause is revealed.

In summary; The PSA test is an important tumor marker used in the diagnosis and post-treatment follow-up of prostate cancer. PSA is produced not only from cancer but also from normal prostate. Elevated PSA suggests prostate cancer in elderly men, but the definitive diagnosis is made by examination, multi-parametric prostate MRI and biopsy. Apart from prostate cancer, there are also conditions that increase PSA. If there is a prostate infection (prostatitis), appropriate antibiotic treatment is given.

Prof. Dr. Emin ÖZBEK

Urology Specialist

Istanbul- TURKEY