Prostate specific antigen, often referred to as PSA, is a protein - or rather, an enzyme - produced by the cells of the prostate gland. Its function is to keep the seminal fluid fluid after ejaculation, so that the spermatozoa can move more easily in the female genital tract. We are therefore talking about a physiological substance with important functions, normally produced also by healthy men.
Although it is produced by some prostate cells, a very small amount of PSA is passed into the blood. Under normal conditions there is a concentration of less than 4 nanograms of PSA per milliliter of blood. For those unfamiliar with conversions, remember that we are talking about 4 billionths of a gram per milliliter of blood. However, what interests us is that PSA concentrations in the blood are related to the health of the prostate. In fact, when prostate cells are damaged, the "loss" of PSA in the bloodstream increases. Since cells are damaged in virtually every prostate disease, when we have high PSA it means that something is probably "bothering" the cells in our prostate. In the next slides we will see in detail what can be the causes of its increase.
PSA is readily detectable in a small sample of blood, usually taken from a vein in the patient's forearm. We have already seen that PSA blood levels below 4 nanograms per milliliter are generally considered normal. Levels higher or higher over time may instead indicate a prostate problem, such as prostatitis, benign prostatic hypertrophy or prostate cancer. Having clarified this, it is essential to specify that PSA is indeed a specific marker of the prostate, but not of the pathologies that affect it. In other words, it tells us that there is a problem in the prostate, but it does not reveal anything about the nature of this problem. For example, the PSA in the blood does not allow us to distinguish with certainty a benign prostate disease from a tumor. In fact, "acute inflammation of the prostate can elevate PSA in the blood in the same way as prostate cancer." But that is not all. The PSA values can in fact be altered by many other conditions, even completely normal. For example, values higher than normal can be recorded after a rectal examination, a prostate biopsy or other maneuvers on the gland performed by the urologist. Furthermore, the PSA can even increase, albeit slightly, even after sexual intercourse; for this, it is normally recommended to abstain from intercourse for at least 48 hours before the test. Other factors that can influence the PSA levels in the blood are the prolonged use of the bicycle and the driving of the motorcycle; in fact, similar activities can give rise to small traumas of the prostate with a consequent increase in PSA. Another very important consideration is that the PSA value varies with age. Consequently, the test result needs to be "interpreted" by the physician on the basis of the patient's age and other conditions not related to a disease state.
In this slide we take a closer look at the diagnostic value of PSA as a tumor marker. In this regard, as you probably already know, PSA is useful in preventive screening programs and in monitoring the disease after treatment. Specifically, PSA levels between 4 and 10 nanograms per milliliter indicate a higher-than-normal risk of cancer, which further increases if levels exceed the 10-nanogram threshold. In addition to the absolute value, in recent times we have tried to analyze other aspects of PSA, in order to correlate it more specifically to prostate cancer. For example, to evaluate the aggressiveness of the tumor and to distinguish between benign and malignant pathology, the speed with which the value increases between one measurement and another is also considered. In fact, it has been noted that a more rapid increase in PSA correlates with a greater probability of prostate cancer.
To further improve the diagnostic specificity of PSA and to obtain additional information, in cases where its level is higher than normal, the free PSA is also often measured and the ratio between free and total PSA is calculated. To better understand, I remind you that the prostate specific antigen measured in the blood constitutes the total PSA. This data includes a free fraction, called free PSA, and another fraction linked to some transport proteins. This last form, complexed with other proteins, constitutes most of the plasma PSA, while the amount of free PSA in the blood is minimal. Differentiating the bound form of PSA from the free one is important. It has been seen, in fact, that under conditions normal, the level of free PSA compared to the total PSA is greater than 20%. Lower values indicate the possible presence of a tumor pathology, while higher values indicate a "benign prostatic hypertrophy or prostatitis. In other words, if the ratio between free PSA and total PSA is greater than 0.20, you can rest assured, as PSA production is probably linked to benign conditions; conversely, when the ratio falls below the 0.20 threshold, the presence of a malignant tumor is more likely.
Another important aspect to consider is that abnormal PSA values often occur even in healthy adults without prostate disorders. In "technical" terms these cases are called false positives. Let me explain: a false positive occurs when the PSA level is high, but the tumor is not present. These cases are quite common, while so-called false negatives are rare, which occur when the PSA level is normal but the tumor is still present. Therefore, in the presence of normal PSA values we can sleep peacefully, while in the face of high values it is not necessary to be too alarmed. For these reasons, PSA has no diagnostic significance and if its levels are altered it is necessary to proceed to further investigations to confirm or exclude prostate cancer. Definitive answers in this regard can, for example, derive from the execution of a prostate biopsy.
In conclusion, we have seen that PSA is certainly a fundamental test in the diagnosis and monitoring of prostate diseases, but it must always be contextualized. For this reason, if the PSA level is elevated or suspected, the information it provides must be integrated with a urological examination, digital rectal examination and other more in-depth investigations that allow to confirm or exclude the diagnosis of cancer of the prostate.
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