Prostate-specific antigen (PSA) is a protein synthesized by prostate cells. Its function is to dissolve the seminal fluid. It is a glycoprotein whose synthesis is exclusive to the prostate.
A scarce part of this PSA passes into the bloodstream of all men.
This PSA that passes into the blood is measured for the diagnosis, prognosis and monitoring of cancer, both localised and metastatic, in this case it is used as a tumour marker.
In other prostate disorders, such as prostatitis and prostatic hyperplasia (adenoma), it can also be increased.
Normal blood levels of PSA in healthy men are very low, on the order of millions of times less than in semen, and only increase when there is prostate disease.
Reference values for serum PSA vary between different laboratories, although the currently accepted normal value is up to 4.0 ng/ml.
Its production depends on the presence of androgens, both testosterone and dihydrotestosterone, and the size of the prostate gland.
It may also be useful in dissolving the cervical mucus layer, allowing the entry of sperm.
Serum PSA concentration is the most sensitive test for early detection of prostate cancer, rising in approximately 65% of cases.
Normally increasing with age, serum PSA levels of 4 ng/mL can be considered high in a 50-year-old person and normal in an 80-year-old.
PSA levels randomly range around 15 % in the same individual. Thus, a PSA test of 3 ng/mL can be repeated on another occasion and could give a result of 3.5 or 2.5 ng/mL naturally.
When prostate cancer develops, PSA levels increase above 4.
If the levels are between 4 and 10, the chance of having prostate cancer is 25%.
If PSA levels are greater than 10, the chance of having prostate cancer is 67% and increases as PSA levels rise.
It has a low sensitivity (35% false negatives) and lack of specificity, as PSA levels can be affected by many factors.
The elevation of PSA in plasma is proportional to the tumor mass present, and so PSA in blood is a great test for detecting prostate cancer.
The more advanced the tumour process, the more often values above normal are found and these are usually higher.
However, a certain percentage of prostate cancer patients have normal PSA levels, in which case the results would be a false negative.
PSA increases with an enlarged prostate, also called benign prostatic hyperplasia or BPH, which occurs in men as they age.
It can also increase in case of irritation, prostatitis, an inflammation of the prostate gland.
The free PSA percentage test indicates how much of the total PSA circulates freely compared to that bound to proteins.
If this test is performed with a low percentage of free PSA (less than 25%), it means that the probability of having prostate cancer increases to 50% and that a diagnostic biopsy is therefore necessary.
If the level of PSA is high, a prostate biopsy is recommended, to determine whether prostate cancer is present.
Patients with prostate cancer have a lower percentage of free PSA, while those with benign prostatic hyperplasia have a higher proportion of free PSA.
Even when the total PSA value is not high, a rapid increase in the time of progression of the PSA value suggests the presence of a cancer, and a biopsy should be considered.
The rate of increase in PSA may have value in the prognosis of diagnosed prostate cancer.
Those men with prostate cancer whose PSA value increases more than 2.0 ng/ml during the year before the cancer is diagnosed are at increased risk.
PSAs in the borderline range (4-10 ng/mL) may be more of a concern for men in their 50s than for those in their 80s.
PSA is known to be normally higher in older men than in younger men, even in the absence of cancer.
It has the ability to detect low levels of PSA, even 0.01 ng/mL.
Although the PSA test is mainly used for early detection of prostate cancer, it is also valid for other situations:
After surgery or radiation therapy, the PSA level can be measured to determine if treatment has been successful.
If the treatment removes or destroys all of the prostate cells, the PSA values usually drop to very low levels.
A later rise in PSA may mean that prostate cancer cells have survived and the cancer has recurred.
PSA levels should be kept at this limit of detectability, because an elevation means that the tumor has recurred.
Recurrence would be suspected by an increase in PSA levels, in which case treatment with an androgen receptor inhibitor called, enzylutamide, would be indicated.
By agreement, it is established that there is biochemical recurrence after radiotherapy when three consecutive increases are detected from the nadir (lowest value) of the PSA, reached after radiotherapy.
From a PSA greater than 10, it is advisable to perform a bone scan.
It can help predict whether the cancer is confined to the prostate gland or outside it. If the PSA level is very high, it is likely that the cancer has gone beyond the limits of the prostate.
This may affect treatment options, such as some types of therapy (surgery or radiation) that are not beneficial if the cancer has spread beyond the lymph nodes or other organs.
During hormone treatment, the PSA level may indicate how well the treatment is working or when it is time to try another type of treatment.
Hormone therapy also lowers PSA levels to baseline values, this time for two reasons: first, because it lowers this androgen-dependent production and second, because it lowers the tumor load.
The American Society of Clinical Oncology recommends that it is not necessary for all men over the age of 50 to be tested for prostate-specific antigen once a year.
Men who are found to have a PSA level of less than one nanogram per milliliter do not have to be re-tested until after five years, because there is a 98 percent chance that the antigen will not increase during that time.
Males with an initial PSA level between 1 and 2 nanograms per milliliter should be tested every two years.
Only when you have a PSA level greater than 2 is it suggested that you have an annual PSA test.
Keywords: what is PSA, what is PSA for, functions of prostate antigen, age variations of PSA, PSA and prostatitis, PSA and benign hyperplasia, PSA and prostate adenoma, PSA and prostate cancer, total and free PSA, hormone treatment and PSA, androgen receptor inhibitor and PSA
-Harrison’s Principles of Internal Medicine. 16th edition. Part V. Oncology and Hematology. Section 1: Neoplastic diseases.
-Tombal B., Borre M., Rathenborg P., Werbrouck P., Van Poppel H., Heidenreich A., et al. (2014) Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study.Lancet Oncol 15: 592-600.