Table of Contents
- What Is Prostate-Specific Antigen and What Is Its Norm?
- How Is PSA measured?
- PSA Marker Indication
- What Is Free PSA?
- Correlation Free/Total PSA
- What Is Speed of Prostate-Specific Antigen Augmentation and the Time of PSA Duplication?
- Types of PSA Test
- What Causes Increase of PSA Level in Blood?
- Rules of Prostate-Specific Antigen Sampling
- Normal Values
- Is Prostate-Specific Antigen the Only Test?
- What if Screening Test Shows Accelerated PSA Level?
- PSA Use for Early Detection of Prostate Carcinoma
- What Are the Prostate-Specific Antigen Test Limits?
- What Is PCA3?
Prostate-specific antigen is protein substance produced by prostatic gland at the cellular level. The deviation of its norm may signify inflammation, adenoma, prostate carcinoma or hypertrophia. The total PSA level is a sum of free and connected forms and is measured by a standard PSA test.
What Is Prostate-Specific Antigen and What Is Its Norm?
Prostate-specific antigen is protein substance produced by prostatic gland at the cellular level. Biochemically prostate-specific antigen belongs to the group of kininogenase protease and is known as human kininogenase-3 (HK-3). After penetrating into semen, PSA dissolves it and enlarges sperm motility necessary for conceiving. The main part of PSA gets into semen, whereas its small amount goes to blood. Therefore, its unit of measurement is nanogram per millimeter (ng/ml). Generally, changes of normal indicator demonstrate the inflammation, adenoma, prostate carcinoma or hypertrophia. But its high level is not always a sign of a malignant tumor. In most cases, this test is assigned to men with diagnosis hypertrophia in order to establish a correct diagnosis.
How Is Prostate-Specific Antigen measured?
PSA is measured by means of blood test. Since the amount of PSA in blood is very low, very sensitive assay technologies are required (monoclonal antibodies procedure). PSA protein may exist in blood in non-connected form (free PSA) or may be connected with other substances (connected/associated PSA). The total PSA level is a sum of free and connected forms and is measured by a standard PSA test.
Prostate-Specific Antigen Marker Indication
PSA test is nowadays considered to be the most reliable and informative blood value used for diagnosis establishment. Antigen is protein substance produced by epithelial cells of male sound gland. Physiological meaning of antigen lies in its impact on prostatic fluid. High activity level if enzymes influence semen and functional characteristics of prostatic gland. In case PSA level is escalated, a man is assigned a number or tests due to which a therapist may diagnose pathology, in particular hyperplasia, oncology or prostatitis. Normal marker indication should not surpass 3,9 ng/ml. Increased test level may be observed among men with diagnosis of prostate carcinoma, whereas low level may be a sign of oncology as well. Prompt PSA analysis will allow making a correct diagnosis and assigning treatment at an early stage of disease establishment. Medical experts recommend men over 50 years of age to make sure to pass this analysis. A man with underlying risk of this disease must undergo this test at the age of 40.
What Is Free PSA?
The main part of PSA protein released into blood is connected with other blood proteins. PSA which is not connected is known as free PSA and it may be measured. It was discovered that the level of free PSA decreased in men who have prostate carcinoma in comparison with those who have benign tumors. Exact level depends on the test which the laboratory uses. As a rule, test result showing less 10% of free PSA may indicate the prostate carcinoma.
Correlation Free/Total PSA
Cancer prostate cells do not produce PSA any longer as contrasted with prostate soft tissue. Therefore, men suffering from prostate carcinoma have a bigger amount of connected PSA in blood serum and lower percent of free PSA of the total one in comparison with the men who do not suffer from prostate carcinoma. Thus, correlation free/total PSA may be used in clinical practice in order to distinguish decrease of PSA in case of benign tumor or prostate carcinoma. This is especially useful for patients with total level of PSA between 4,0 and 10,0 ng/ml and negative result of rectal examination in order to help a doctor reach a decision about the necessity of prostate biopsy.
During one of the research studies, prostate carcinoma was discovered among 56% of men with correlation free/total PSA less than 0,10 and only among 8% of men with correlation free/total PSA more than 0,25. Nevertheless, concentration of free PSA must be used with care, since some factors, such as temperature, prostate size may affect the correlation free/total PSA. Moreover, measurement of free PSA is not clinically useful for patients with marker of total PSA in blood serum less than 10,0 ng/ml.
What Is Speed of PSA Augmentation and the Time of PSA Duplication?
Change of PSA level with the course of time may be used for estimation of both risk of carcinoma development and particular tumor aggression. Speed of PSA augmentation is defined as absolute annual gain of PSA in blood serum (ng/ml/annum). Time of PSA duplication is defined as an exponential growth of PSA with the course of time and indicates the fractional change. These two measures may have prognostic meaning for patients who are treated for prostate carcinoma. Nevertheless the research studies have shown that the usage of these values of PSA measurements for prostate carcinoma diagnosis does not give additional information in comparison with PSA level alone.
Types of Prostate-Specific Antigen Test
Prostatic-specific antigen in blood may exist in three conditions:
- Free condition – PSA is not connected with serum protein;
- Connection with chymotrypsin – blood enzyme characterized by high activity;
- Connection with macroglobulin – serum protein.
These connections underlie diagnosis of prostatic gland among which there are the following types:
- Total PSA level showing antigen in free condition and in connection with chymotrypsin;
- Free prostate-specific antigen;
- Correlation of total PSA to free PSA.
» While assigning PSA test, urologist must indicate which of the afore-mentioned indicators should be studied. As a rule, this is a total ratio. In case of its surpass, an expanded analysis is assigned which includes the two remaining indicators: free and correlation of total ratio of PSA to free PSA.
What Causes Increase of Prostate-Specific Antigen Level in Blood?
It is recognized that increase of PSA in blood is connected with its release in circulation because of prostatic gland structure distortion. This may occur due to various diseases of prostatic glad including prostate carcinoma. It is worth mentioning that PSA is not specific for prostate carcinoma, but its increase in blood may demonstrate some prostate disorders. The most frequent cause of PSA level increase is benign prostatic hyperplasia (enlargement of prostatic gland) and prostatitis (inflammation of prostatic gland). Nevertheless, increase of PSA level may happen due to other causes, such as ejaculation, transrectal US, cystoscopic examination, urinary catheterization with soft catheter, and prostate biopsy. Thus, men who decide to pass PSA test must remember of these important factors which may affect the results. Age and prostate volume may also influence PSA test results.
Rules of Prostate-Specific Antigen Sampling
In order to have maximally accurate results, a patient has to observe particular rules while preparing to the test, blood test delivery and receiving the result.
Each doctor wants to get consistent results of analysis. Therefore, in order to avoid incorrect indicators, a patient has to refuse alcoholic beverages, smoking, spicy and roasted food 1-2 days before delivery of medical tests. Analysis is taken only on an empty stomach; a patient may drink only fresh water. Also, it is not recommended practicing sport, jogging, working in his fitness and other physical activities. Exclude sexual intercourse for a short while.
Delivery of blood test
Blood is taken from vein strictly before 11 AM, since blood corpuscles are not destructed exactly at that time. The test is categorically prohibited if a patient underwent the following tests one week before blood test delivery: digital rectal examination, cystoscopic examination, prostate milking, laser action on prostatic gland, ergometry, transrectal ultrasound investigation, endoscopic examination of the colon. Besides, the analysis efficiency may be affected by urological conditions, such as oncology, heart attack, inflammatory process in gland, benign prostatic hyperplasia.
The exceed of norm is a first sign of oncology. Nevertheless increased concentration may signify the presence of other diseases.
Antigen level may vary in accordance with:
- Age range. The disease is more frequent in aged patient. Their PSA level is slightly oversized in comparison with young men.
- Medical drugs. Many medicines are capable to alter the test level in particular those remedies which are applied for the disease treatment.
- False-positive test. This indicator occurs in case when the marker level is higher not due to oncology but as a result of other causes, such as prostatitis or prostate carcinoma.
It should be borne in mind that even the standard procedure such as digital rectal examination may change the test results. In order to achieve more accurate indicators, specialists improve them by using PSA coefficient which allows providing exact accuracy of analysis and estimating the relation of free PSA to associated antigen. Nowadays, medical experts have stated the fact that escalation of associated antigen is characteristic for oncology, whereas free marker reveals prostate carcinoma.
The average normal values must not exceed 4 ng/ml. If markers correspond to below-listed norms, a patient may not worry in regards to oncology. Nevertheless, while examining the results, one significant condition should be taken into account: man’s age.
Standard indicators of age and antigen level:
- From 40 to 50 years of age – 0-2,5 ng/ml;
- From 50-60 years of age – 0-3,5 ng/ml;
- From 60 to 70 years of age – 0-4,5 ng/ml;
- From 70 to 80 years of age – 4-6,5 ng-ml.
Exceed of antigen level is connected not only with age, but also with gland volume increase due to benign tumor. Antigen level is also affected by prostatic gland volume, and this indicator should be taken into account because oncology is met among 50% of patients suffering from benign prostatic hyperplasia.
Is Prostate-Specific Antigen the Only Test?
Usage if PSA test for screening of prostate carcinoma is a matter of dispute, since in reality it is not clear whether the results of tests are accurate and allow saving patient’s life. Nowadays, there are many research studies of tests which may substitute PSA analysis. But there are no more efficient and specific marker allowing reveling prostate carcinoma. Notwithstanding all attempts, they all failed. The developed markers have a number of drawbacks in comparison with PSA analysis, the one of which is high price.
What if Screening Test Shows Accelerated PSA Level?
If a man has no symptoms of prostate carcinoma but he takes decision of undergoing screening and the high PSA level is detected, a doctor may recommend passing a second PSA test. If PSA level is still high, a doctor will assign to continue PSA tests and digital rectal examination (DRE) in regular time intervals for observation of any changes with the course of time. If PSA level continues increasing and DRE causes suspicions, a doctor will assign additional tests for finding out the origin of the disorder. Urine analysis may be recommended for exposing of urinary tract infections. Also, transrectal US, x-ray, and cystoscopic examination may be assigned. In case prostate carcinoma is suspected, a doctor may appoint prostate biopsy. During this procedure several samples of prostate tissue are selected by means of introduction of hollow needle to prostatic gland. More often needles are introduced via rectum paries (transrectal biopsy), but needles may also be introduced through skin between scrotum and anus (transperineal biopsy). Then a pathologist analyses the collected tissues under the microscope. During biopsy a doctor may use ultrasound. Nevertheless, ultrasound alone may not be used for prostate carcinoma diagnostics.
PSA Use for Early Detection of Prostate Carcinoma
Generally, clinically localized prostate carcinoma does not have any clinical symptoms. As a rule, men feel good and biopsy for prostate carcinoma revealing is initiated after abnormal results of DRE and/or abnormal PSA marker. Thus, in clinical practice the tests of prostate carcinoma detection include measurement of PSA level in blood serum, digital rectal examination and transrectal ultrasonic examination.
PSA level is an independent variable for prostate carcinoma prognosis. Its high level demonstrates high possibility if prostate carcinoma. Generally, abnormal result requires additional testing. Nevertheless, the final diagnosis of prostate carcinoma depends on presence of cancer cells found after prostate biopsy or in surgical samples.
As a rule, PSA level showing more than 4,0 ng/ml is considered to be suspicious. After the increase of the level to 10,0 ng/ml the possibility of cancer grows. Anyway, not all men with prostate carcinoma have increased PSA level. It is well known that prostate carcinoma cases may be observed with PSA level of less than 4,0 ng/ml. That is why doctors may use the lower boundaries in order to decide when biopsy is important.
What Are the Prostate-Specific Antigen Test Limits?
PSA level is a continuous parameter. Its high marker increases the probability of prostate carcinoma. On the contrary, prostate carcinoma may appear regardless of low PSA levels. The recent research study in the USA has discovered prostate carcinoma among 6,6% of men with PSA level equal to more than 0,5 ng/ml. That is why there is no generally accepted level showing the absence of prostate carcinoma. In combination with absence of molecular markers for exposure of prostate carcinoma, another contradiction of PSA screening is the fact that not all men suffering from prostate carcinoma decease of it.
According to the afore-mentioned causes, it is important not to rely exclusively on PSA analysis of blood. The most useful additional test is physical examination of prostatic gland by a doctor, known as digital rectal examination. These studies show that combination of PSA and DRE improve the total level of prostate carcinoma revealing.
What Is PCA3?
New biomarker is known as PCA3. In comparison with PCA and free PCA, this biomarker is superior to them in early diagnostics of prostate carcinoma. PCA3 was initially applied for comparison of prostate tissues affected by cancer with benign normal prostate tissues. Whereas PCA is revealed in blood, PCA3 is measured in urine taken after prostate milking. The main advantages of PCA3 include its hypersensitivity and specificity in comparison with PCA. In particular, PCA3 may be used for revealing of prostate carcinoma in men who initially had negative biopsies regardless of increased PCA. That is why PCA3 test may allow decreasing the number of potentially unimportant biopsies, resulted from unspecific positive PCA screenings. Notwithstanding its promising perspectives in assistance to doctors and proving of biopsy indicators, PCA3 test application is still considered to be experimental.