Prostate specific antigen, or PSA, has been widely used in clinical practice for more than 20 years, and it is of great importance in the diagnosis and management of prostate cancer, as it enables the diagnosis of prostate cancer 5-8 years earlier, and to some extent changes the situation that most patients are diagnosed only at advanced stages. What is prostate-specific antigen? What is the significance of its elevation? Please see below for more information. The Prostate Specific Antigen is a single chain glycoprotein, and in clinical work, we generally consider PSA to be a prostate-specific biological indicator that is produced primarily by the glandular epithelial cells of the prostate. Under normal conditions, PSA is secreted into the prostatic fluid or semen and participates in the liquefaction process of semen. In normal prostate tissue, almost all of the PSA can only enter the seminal fluid through the lumen of the prostate ducts and not into the bloodstream because of a dense structure called the basement membrane beneath the epithelial cells. Therefore, the concentration of PSA in serum is very low in normal people. However, when the barrier consisting of the basal lamina and basement membrane of the normal prostate gland is lost to produce, PSA can be released into the blood through this barrier. The elevation of PSA in the blood may be caused by the disruption of this tissue structure in the prostate gland. This can occur in the presence of prostate disease (BPH, prostatitis, prostate cancer) and during manipulation of the prostate gland (prostate massage, prostate biopsy). Although some studies have found that prostate cancer cells may produce less PSA than normal prostate tissue, significantly elevated PSA can be detected in the blood due to this structural disruption. Both bound and unbound (fPSA) forms exist in the serum and are predominantly bound, with the sum of the two being the total PSA (tPSA). In the event of prostate cancer, we can observe a significant increase in total PSA and a decrease in free PSA (PSA) in the patient’s blood. 20 years of clinical use have shown that serum PSA testing is convenient (only 2 ml of blood needs to be drawn on the day of testing), accurate, and it helps in the early diagnosis of prostate cancer, monitoring treatment response and determining prognosis. This test is now available in most hospitals. What is the significance of an elevated PSA? Early studies have found that the reference value of PSA in normal human serum ranges from 0-4 ng/ml, and it has been controversial how to choose a suitable threshold value for PSA so that prostate cancer can be detected in patients above this value for further examination. This is because 20% of prostate cancer patients have a normal PSA because the tumor is small or the cancer cells do not secrete PSA, while some have an elevated PSA for other reasons. However, it is still widely accepted that there is a correlation between the level of PSA and the risk of prostate cancer, and that a PSA of 4-10 ng/ml with normal prostate examinations (rectal examinations, imaging) is associated with a higher risk of prostate cancer in about 25% of patients. The risk of prostate cancer is 49% when PSA is 10.1-20ng/ml; when PSA is greater than 20ng/ml, the risk of prostate cancer is 68%. This means that the higher the PSA, the greater the risk of diagnosis of prostate cancer. The current clinical practice refers to PSA in the range of 4-10ng/ml as the gray zone of PSA, as it is not a satisfactory indicator of prostate cancer. Therefore, scientists have worked extensively to discover several novel PSA tests to aid in the diagnosis of prostate cancer. The free PSA to total PSA ratio (fPSA/tPSA %) is generally considered to be greater in the serum of normal subjects and BPH patients, while the ratio of FPSA is smaller in prostate cancer patients. Therefore, when the tPSA test result is in the gray zone, testing this indicator is helpful for disease analysis. When it is less than 0.1, the risk of prostate cancer is 56%; when it is 0.1-0.15, the risk of prostate cancer is 28%; when it is 0.15-0.20, it is 20%; when it is 0.20-0.25, it is 16%; and when it is greater than 0.25, it is 8%. In other words, the smaller this value is, the greater the possibility of diagnosis of prostate cancer. 2. The significance for prognosis judgment PSA is one of the three important factors of prostate risk level, prostate cancer can be classified into low risk, intermediate risk and high risk according to these three factors. The higher the grade, the greater the risk of invasion, metastasis and recurrence, and the shorter the survival period may be. PSA less than 10ng/ml is generally classified as low risk, 10-20ng/ml as intermediate risk, and greater than 20ng/ml as high risk. The higher the level of PSA before treatment, the higher the risk of prostate cancer invasion and metastasis. 3. Significance for disease monitoring Relapse after radiotherapy: PSA may be elevated in patients during radiotherapy, not necessarily caused by relapse; PSA may also fluctuate up and down after radiotherapy. The current consensus is that PSA levels above the minimum level of 2ng/ml can be considered as a relapse, but at present this value is not an indicator of the need for clinical intervention. Recurrence after radical surgery: Currently, two consecutive PSA levels greater than 0.2ng/ml are considered as the criteria for recurrence of prostate cancer after radical surgery. Factors affecting PSA test results As mentioned earlier, PSA is a prostate-specific, but not a prostate cancer-specific, indicator. A variety of other factors may contribute to elevated PSA levels, such as benign prostatic hyperplasia, infections (prostatitis, bacterial cystitis, which may show a significant decrease in PSA after antibiotic treatment), related operations (cystoscopy, prostate massage, prostate biopsy, prolonged walking and bicycling), ejaculation (where PSA appears elevated over a short period of time), aging, etc. However, studies have found that gentle prostate finger examinations do not lead to significant changes in PSA. There are other factors that can cause a decrease in PSA: taking medications related to prostate enlargement (finasteride and dutasteride application for 9-12 months can cause a 50% decrease in PSA) as well as androgen-blocking medications, depot (removal of testicles or commenting on related medications), etc. In addition, some therapeutic measures can affect PSA levels: surgical procedures such as prostatectomy or partial prostatectomy can lead to a significant short-term increase in PSA but a subsequent decrease; PSA levels can also increase during and shortly after radiotherapy but then decrease. In addition, differences in testing methods can have a significant impact on PSA results. When PSA test results are abnormal, we need to pay high attention to detect the presence of prostate cancer in time for timely treatment.