The PSA Test
1. How is it used?
2. When is it ordered?
3. What does the test result mean?
How is it used?
The PSA test and digital rectal exam
(DRE) may be used to screen both
asymptomatic and symptomatic men
for prostate cancer. PSA is a protein
produced primarily by cells in the prostate and most of the PSA is released into semen, but small amounts of it are also released
into the blood. PSA exists in two
forms in the blood: free (not bound) and complexed (cPSA, bound to other proteins). Lab tests can measure free PSA or total PSA (bound plus unbound).
Some organizations, such as the U.S. Preventive Services Task Force, feel that the harms associated with over-diagnosis and over-treatment outweigh the potential benefits and advise against using PSA to screen for prostate cancer in healthy men of any age. The American Cancer Society and the American Urological Association recommend that men discuss the advantages and disadvantages of PSA-based screening for prostate cancer with their healthcare provider before making an informed decision about whether to be screened or not.
While elevated PSA levels are associated with cancer, they may be caused by other conditions, such as benign prostatic hyperplasia (BPH) and inflammation of the prostate. An elevated PSA may be followed by a biopsy, which has risk of complications such as pain, fever, blood in the urine, or urinary tract infection. (Read the article on Anatomic Pathology for more information about biopsies.)
And though prostate cancer is a relatively common type of cancer in men and the number two cause of death, many prostate cancers are slow-growing. These slow-growing types may never cause symptoms or become life-threatening. Yet prostate cancer found through screening may be treated with surgery or radiation therapy, which can have serious side effects, such as incontinence or erectile dysfunction. The total PSA test can be elevated temporarily for a variety of reasons, so if an initial PSA is elevated, another PSA may be done a few weeks after the first to determine if the PSA is still elevated. If the repeat test is elevated, a healthcare provider may recommend that series of PSAs be done over time to determine whether the level goes down, stays elevated, or continues to increase. In cases where the cancer appears to be slow-growing, the healthcare provider and patient may decide to monitor its progress rather than pursue immediate treatment (called "watchful waiting").
If the DRE is normal but the PSA is moderately elevated, a free PSA test may be used to look at the ratio of free to total PSA. This can help to distinguish between prostate cancer and other non-cancer causes of elevated PSA.
Other tests may also be recommended if either the PSA or the DRE is found to be abnormal. A urinalysis may be done, for example, to check for urinary tract infection and imaging tests, such as an ultrasound, may be done to examine the prostate.
If prostate cancer is diagnosed, the total PSA test may be used as a monitoring tool to help determine the effectiveness of treatment. It may also be ordered at regular intervals after treatment to detect recurrence of the cancer.
When is it ordered?
For men who wish to be screened for prostate cancer, the American Cancer Society recommends that healthy men of average risk consider waiting to get tested until age 50, while the American Urological Association recommends screening for men between the ages of 55 and 69 with no routine screening after age 70.
For those at high risk, such as American men of African descent and men with a family history of the disease, the recommendation is to consider beginning testing at age 40 or 45. (See Screening Tests for Adults (30-49): Prostate cancerand Screening Tests for Adults (50 and Up): Prostate cancer for details on screening recommendations.) The total PSA test and digital rectal exam (DRE) may also be ordered when a man has symptoms that could be due to prostate cancer, such as difficult, painful, and/or frequent urination, back pain, and/or pelvic pain.
If a total PSA level is elevated, a healthcare provider may order a repeat test a few weeks later to determine whether the PSA concentrations have returned to normal.
A free PSA is primarily ordered when a man has a moderately elevated total PSA. The results give the healthcare provider additional information about whether the person is at an increased risk of having prostate cancer and help with the decision of whether to biopsy the prostate. The total PSA may be ordered at regular intervals during treatment of men who have been diagnosed with prostate cancer and when a man with cancer is participating in "watchful waiting" and not currently treating his prostate cancer.
What does the test result mean?
PSA test results can be interpreted a number of different ways and there may be differences in cutoff values between different laboratories.
The value for total PSA below which the presence of prostate cancer is considered to be unlikely is 4.0 ng/ml (nanograms per milliliter of blood). There are some that feel that this level should be lowered to 2.5 ng/ml in order to detect more cases of prostate cancer. Others argue that this would lead to more over-diagnosing and over-treating cancers that are not clinically significant.
There is agreement that men with a total PSA level greater than 10.0 ng/ml are at an increased risk for prostate cancer (more than a 50% chance, according to the American Cancer Society (ACS)).
Total PSA levels between 4.0 ng/ml and 10.0 ng/ml may indicate prostate cancer (about a 25% chance, according to the ACS), benign prostate hyperplasia (BPH), or inflammation of the prostate. These conditions are more common in the elderly, as is a general increase in PSA levels. Total PSA between 4.0 ng/ml and 10.0 ng/ml is often referred to as the "gray zone." It is in this range that the free PSA may be useful (see next bullet).
Free PSA—prostate tumors typically produce mostly complexed PSA (cPSA), not free PSA. Benign prostate cells tend to produce more free PSA, which will not complex with proteins. Thus, when men in the gray zone have decreased levels of free PSA, it means that they have increased cPSA and a higher probability of prostate cancer. Conversely, when they have elevated levels of free PSA and low cPSA, the risk is diminished. The ratio of free to total PSA can help the individual and his healthcare provider decide whether or not a prostate biopsy should be performed.
Additional evaluations of the PSA test results are sometimes used in an effort to increase the usefulness of the total PSA as a screening tool. They include:
PSA velocity—the change in PSA concentrations over time; if the PSA continues to rise significantly over time (at least 3 samples at least 18 months apart), then it is more likely that prostate cancer is present. If it climbs rapidly, then the affected person may have a more aggressive form of cancer.
PSA doubling time—another version of the PSA velocity; it measures how rapidly the PSA concentration doubles.
PSA density—a comparison of the PSA concentration and the volume of the prostate (as measured by ultrasound); if the PSA level is greater than what one would expect given the size of the prostate, the chance that a cancer is present may be higher.
Age-specific PSA ranges—since PSA levels naturally increase as a man ages, it has been proposed that normal ranges be tailored to a man's age. During treatment for prostate cancer, the PSA level should begin to fall. At the end of treatment, it should be at very low or undetectable levels in the blood. If concentrations do not fall to very low levels, then the treatment has not been fully effective. Following treatment, the PSA test is performed at regular intervals to monitor the person for cancer recurrence. Since even tiny increases can be significant, those affected may want to have their monitoring PSA tests done by the same laboratory each time so that testing variation is kept to a minimum. A test called "ultrasensitive PSA" (USPSA) may be useful in monitoring for persistence or recurrence of cancer after treatment. This test detects PSA at much lower levels than the traditional test. It has been suggested that increases in PSA due to the persistence or return of cancer can be identified much sooner with this test. However, results of this test must be interpreted with caution. Because the test is very sensitive, there can be small increases in PSA levels from one time to the next even when no cancer is present (false positive).
Semen Analysis (Spermiogram)
Semen Analysis is to evaluate the fluid and content ejaculated from penis for volume and quality. This test both analysis the fluid portion which is called semen and the moving cells which are called sperms and seen only under a microscope. It is the most important and Initially asked laboratory testing in Evaluation of fertility potential in men.
Semen is viscous and off-white fluid that contains the sperms and other fluids secreted by various glands. It is highly viscous immediately after ejaculation then becomes fluidal afterwards within 10-30 minutes. Sperms are moving reproductive cells which are composed of a head and tail. The sperms enter the body of the female, move toward and fuse with the ovum, which is called fertilization. Each semen sample contains millions of sperms; different amounts of fructose; buffer fluids; coagulation agents; lubricants; and enzymes to support sperms and aid fertilization.
Also in semen analysis, semen sample can be washed to get information for planning a treatment method. This test is performed following a 3-5-day sexual abstinence to get important information about what treatment method would give the better outcomes. A typical semen analysis measures the following parameters:
Volume and viscosity of semen
Sperm concentration (density)
Total number of sperms
Sperm motility (percentage of moving sperms and the way the sperms move)
Number of Normal and non-normal (damaged) sperms
Coagulation and liquefaction
Fructose (a type of sugar in semen), pH (acidity)
Number of immature sperms
Leucocytes (white blood cells) ,number of infected cells
How to collect sperm for testing?
It is preferable to collect a semen sample at the center just before analyzing since it must be analyzed within an hour. Semen is collected in a private room reserved for this procedure. By masturbating the person collects his semen sample in a special container.
You’ll need to refrain from ejaculation for 2 to 5 days prior to testing in order to obtain optimum sperm count. Please follow the instructions carefully.
Where to use this test?
Semen analysis is a test used to determine the fertility potential of a man. Semen analysis evaluates a number of parameters for semen and sperms. A semen analysis should be evaluated with at least two samples taken 2-3 weeks apart because the number of sperms and density of semen can vary day by day and some conditions are likely to affect sperm levels.
When is a test required?
Semen analysis is required when a clinician considers that a couple or an individual has a problem with fertility. At least 10-20% of couples have difficulty in having a child. If the infertility arises from the male, a semen analysis will be required to determine what inhibits fertility and applicability of assisted reproduction techniques to achieve pregnancy. If the semen analysis gives abnormal outcomes, the test is repeated in a certain time decided by the doctor. What do test results mean?
The volume of collected semen is approximately 2-6 milliliters. The volume of semen less than this indicates the scarcity of total number of sperms which affects fertility. The volume of sperm greater than this indicates a higher amount of fluid which reduces sperm concentration. Semen needs to be viscous when first collected then becomes fluidal within 10-30 minutes. If this is not the case, motility of sperms is restricted.
Sperm concentration is highly important for being able to fertilize the ovum. A sperm concentration less or greater than particular levels might indicate a fertility problem.
It is therefore an important parameter evaluated with spermiogram. Sperm concentration is number of millions of sperms in one milliliter of semen. In a normal concentration, 20 millions and over per milliliter in one ejaculation and total number of sperms is 40 millions and over.
Motility is the percentage of moving sperms in one sample and indicates the direction and rate of their move. Motility of sperms is also important for being able to fertilize the ovum because only moving sperms can go down the female genital tracts and fertilize the ovum. At least 50% of sperms should be able to move and swiftly travel on a straight line in an hour after ejaculation. The move of the sperm is classified from 0 (immotile) to 4, and 3 and 4 represent good motility. Morphology (form and appearance) Another important factor for fertilization capacity is form of the sperm and whether any structural deformations are present. It is not possible for a deformed sperm to fertilize the ovum. Morphology parameter indicates the form of the sperm and analyzes the size, form and appearance of sperms. To evaluate this parameter, 200 sperms are analyzed and the deformed ones are noted. Morphological evaluation is performed by Kruger’s criteria at our center. The greater number of abnormal sperms, the less the likelihood of fertility is. Abnormal form includes anomaly of head, neck and tail, and immature forms.
It is a test to see vitality of sperms in semen. This test involves eosin staining and is applied on persons with less than 50% of sperms moving. So, it is evaluated whether immotile sperms are alive. This test is also called as sperm life test.
Peroxidase staining test (leukocyte testing)
There are other cells in semen in addition to sperms. Leukocytes (white cell count) are routinely evaluated in a semen analysis since they can be a predictor of an existing or previous infection. With this test called “Leucoscreen”, particular information can be obtained by number of leukocytes in semen. Normally, the number of leukocytes should be less than 1 million per ml in semen.
Semen acid-base balance (pH)
pH of semen is measured by a specific paper of which color is changed by pH. pH of normal semen gives an alkali value between 7.2 and 7.8. While a prostatic secretion is acidic, a seminal vesicle is alkali. The value of pH can be affected by a problem with one or more glands. pH value might not have major effects on infertility potential in men. In evaluation of fertility in men, each parameter of semen analysis is evaluated separately and as a whole. Each parameter of semen analysis affects fertility; however the outcomes might not present the final results. Individuals with poor results of semen analysis could have children whereas individuals with better results could experience difficulties.
The Chemical Examination
To perform the chemical examination, we use commercially prepared test strips with test pads that have chemicals impregnated into them. The laboratorian dips the strip into urine, chemical reactions change the colors of the pads within seconds to minutes, and the laboratorian determines the result for each test. To reduce timing errors and eliminate variations in color interpretation, we use automated instruments frequently to "read" the results of the test strip.
In our office we do the chemical examination in conjunction followed by a microscopic examination of the urine if there are any abnormal results. Results from both sets of tests are then considered together for interpretation. Abnormal findings may be followed by additional urine cultures and/or blood tests.
The most frequently performed chemical tests using reagent test strips are:
Specific Gravity (SG)
Blood (hemoglobin) and Myoglobin
Specific Gravity (SG)
Specific gravity is a measure of urine concentration. This test simply indicates how concentrated the urine is. Specific gravity measurements are a comparison of the amount of substances dissolved in urine as compared to pure water. If there were no substances present, the specific gravity of the urine would be 1.000 (the same as pure water).
As with specific gravity, there are typical but not "abnormal" pH values. The urine is usually slightly acidic, about pH 6, but can range from 4.5-8. The kidneys play an important role in maintaining the acid-base balance of the body. Therefore, any condition that produces acids or bases in the body, such as acidosis or alkalosis, or the ingestion of acidic or basic foods can directly affect urine pH.
The protein test pad provides a rough estimate of the amount of albumin in the urine. Albumin makes up about 60% of the total protein in the blood. Normally, there will be no protein or a small amount of protein in the urine. When urine protein is elevated, a person has a condition called proteinuria.
Proteinuria may occasionally be seen in healthy individuals. Healthy people can have temporary or persistent proteinuria due to stress, exercise, fever, aspirin therapy, or exposure to cold, for example. Repeat testing may be done once these conditions have resolved to determine whether the proteinuria is persistent.
Glucose is normally not present in urine. When glucose is present, the condition is called glucosuria. It results from either:
1. An excessively high glucose level in the blood, such as may be seen with people who have uncontrolled diabetes
2. A reduction in the "renal threshold;" when blood glucose levels reach a certain concentration, the kidneys begin to eliminate glucose into the urine to decrease blood concentrations. Sometimes the threshold concentration is reduced and glucose enters the urine sooner, at a lower blood glucose concentration.
Some other conditions that can cause glucosuria include hormonal disorders, liver disease, medications, and pregnancy. When glucosuria occurs, other tests such as a fasting blood glucose are usually performed to further identify the specific cause.
Ketones are not normally found in the urine. They are intermediate products of fat metabolism. They are produced when glucose is not available to the body's cells as an energy source. They can form when a person does not eat enough carbohydrates (for example, in cases of fasting, starvation, or high-protein diets) or when a person's body cannot use carbohydrates properly. When carbohydrates are not available, the body metabolizes fat instead to get the energy it needs to keep functioning. Strenuous exercise, exposure to cold, frequent, prolonged vomiting, and several digestive system diseases can also increase fat metabolism, resulting in ketonuria.
Blood (Hemoglobin) and Myoglobin
This test is used to detect hemoglobin in the urine (hemoglobinuria). Hemoglobin is an oxygen-transporting protein found inside red blood cells (RBCs). Its presence in the urine indicates blood in the urine (known as hematuria).
A small number of RBCs are normally present in urine and usually result in a "negative" chemical test. An increased amount of hemoglobin and/or increased number of RBCs are detected as a "positive" chemical test result. Results of this test are typically interpreted along with those from the microscopic examination of the urine to determine whether RBCs are present in the urine. A positive result on this test with no RBCs present may indicate the presence of hemoglobin in the urine (which can occur when RBCs have broken apart) or myoglobin from muscle injury.
Blood in the urine is not a normal finding, but it is not uncommon and not necessarily a cause for alarm. Your healthcare practitioner will investigate further to try to determine the source and underlying cause of the blood and may request repeat testing to determine whether the blood is persistent.
Leukocyte esterase is an enzyme present in most white blood cells (WBCs). A few white blood cells are normally present in urine and usually give a negative chemical test result. When the number of WBCs in urine increases significantly, this screening test will become positive. Results of this test will be considered along with a microscopic examination for WBCs in the urine.
When this test is positive and/or the WBC count in urine is high, it may indicate that there is inflammation in the urinary tract or kidneys. The most common cause for WBCs in urine (leukocyturia) is a bacterial urinary tract infection (UTI), such as a bladder or kidney infection. In addition to WBCs, bacteria and RBCs may also be seen in the microscopic examination. Ifbacteria are present, the chemical test for nitrite may also be positive (see below).
This test detects nitrite and is based upon the fact that many bacteria can convert nitrate (a normal substance in urine) to nitrite. Normally, the urinary tract and urine are free of bacteria and nitrite. When bacteria enter the urinary tract, they can cause a urinary tract infection. A positive nitrite test result can indicate a UTI. However, since not all bacteria are capable of converting nitrate to nitrite, someone can still have a UTI despite a negative nitrite test. The results of this test will be considered along with the leukocyte esterase (above) and a microscopic examination.
This test screens for bilirubin in the urine. Bilirubin is not present in the urine of normal, healthy individuals. It is a waste product that is produced by the liver from the hemoglobin of RBCs that are broken down and removed from circulation. It becomes a component of bile, a fluid that is released into the intestines to aid in food digestion. In certain liver diseases, such as biliary obstruction or hepatitis, excess bilirubin can build up in the blood and is eliminated in urine. The presence of bilirubin in urine is an early indicator of liver disease and can occur before clinical symptoms such asjaundice develop.
Ascorbic Acid (Vitamin C)Occasionally, people taking vitamin C or multivitamins may have large amounts of ascorbic acid in their urine. When this is suspected to be the case, a laboratorian may test the sample for ascorbic acid (vitamin C) because it has been known to interfere with the accuracy of some of the results of the chemical test strip, causing them to be falsely low or falsely negative. Examples of tests that may be affected include the urine dipstick tests for glucose, blood, bilirubin, nitrite, and leukocyte esterase.
The Microscopic Examination
The microscopic exam is performed on urine sediment – urine that has been centrifuged to concentrate the substances in it at the bottom of a tube. The fluid at the top of the tube is then discarded and the drops of fluid remaining are examined under a microscope. Cells, crystals, and other substances are counted and reported either as the number observed "per low power field" (LPF) or "per high power field" (HPF). In addition, some entities, if present, are estimated as "few," "moderate," or "many," such as epithelial cells, bacteria, and crystals. Cells and other substances that may be seen include the following:
Red Blood Cells (RBCs)
White Blood Cells (WBCs)
Bacteria, Yeast and Parasites
Red Blood Cells (RBCs)
Normally, a few RBCs are present in urine sediment (0-5 RBCs per high power field, HPF). A positive chemical test for hemoglobin and an increase in the number of RBCs seen under the microscope indicates that there is blood in the urine. However, this test cannot be used to identify where the blood is coming from.
Blood in the urine is not a normal finding, but it is not uncommon and is not necessarily a cause for alarm. Hematuria is a sign or an indicator that prompts a healthcare practitioner to investigate further to try to determine the underlying cause of the blood.
White Blood Cells (WBCs)
The number of WBCs in urine sediment is normally low (0-5 WBCs per high power field, HPF). WBCs can be a contaminant, such as those from vaginal secretions.
An increased number of WBCs seen in the urine under a microscope and/or positive test for leukocyte esterase may indicate an infection or inflammation somewhere in the urinary tract. If also seen with bacteria (see below), they indicate a likely urinary tract infection.
Epithelial cells are usually reported as "few," "moderate," or "many" present per low power field (LPF). Normally, in men and women, a few epithelial cells can be found in the urine sediment. In urinary tract conditions such as infections, inflammation, and malignancies, an increased number of epithelial cells are present. Determining the kinds of cells present may sometimes help to identify certain conditions. For example, epithelial cells containing large amounts of broken-down hemoglobin (called hemosiderin) may indicate that there were red blood cells or hemoglobin in the urine recently, even if there are none now.
Bacteria, Yeast and Parasites
In healthy people, the urinary tract is sterile and, if the urine sample is collected as a "clean-catch" sample, there will be no microbes seen in the urine sediment under the microscope. Special care must be taken during specimen collection, particularly in women, to prevent bacteria that normally live on the skin or in vaginal secretions from contaminating the urine sample.
Bacteria from the surrounding skin can enter the urinary tract at the urethra and move up to the bladder, causing a urinary tract infection (UTI). If the infection is not treated, it can eventually move to the kidneys and cause kidney infection (pyelonephritis). If a person has an uncomplicated lower urinary tract infection, then the person may be treated without need for a urine culture. However, if the person has had recurrent UTIs, suspected complicated infection, or is hospitalized, a urine culture and susceptibility testing may be performed to help guide treatment. (See the article on Urine Culture for details.)
In women (and rarely in men), yeast can also be present in urine. They are most often present in women who have avaginal yeast infection because the urine has been contaminated with vaginal secretions during collection. If yeast are observed in urine, then the person may be treated for a yeast infection.
Trichomonas vaginalis is a parasite that may be found in the urine of women, or rarely, men. As with yeast, T. vaginalisinfects the vaginal canal and their presence in urine is due to contamination during sample collection. If these are found during a urinalysis, then Trichomonas testing may be performed to look for a vaginal infection.
Casts are cylindrical particles sometimes found in urine that are formed from coagulated protein released by kidney cells. They are formed in the long, thin, hollow tubes of the kidneys known as tubules and usually take the shape of the tubule (hence the name). Under the microscope, they often look like the shape of a "hot dog" and in healthy people they appear nearly clear. This type of cast is called a "hyaline" cast. Normally, healthy people may have a few (0–5) hyaline casts per low power field (LPF). After strenuous exercise, more hyaline casts may be detected.
Urine contains many dissolved substances (solutes) – waste chemicals that the body needs to eliminate. These solutes can form crystals, solid forms of a particular substance, in the urine if: 1. The urine pH is increasingly acidic or basic; 2. The concentration of dissolved substances is increased; and 3. The urine temperature promotes their formation.
Crystals are identified by their shape, color, and by the urine pH. They may be small, sand-like particles with no specific shape (amorphous) or have specific shapes, such as needle-like. Crystals are considered "normal" if they are from solutes that are typically found in the urine; these usually form as urine cools after collection and were not present in the body. Some examples of crystals that can be found in the urine of healthy individuals include:
Crystalline uric acid
If the crystals are from substances that are not normally in the urine, they are considered "abnormal." Abnormal crystals may indicate an abnormal metabolic process.
A urine culture is a test that can detect bacteria in your urine. This test can find and identify the germs that cause a urinary tract infection (UTI). Bacteria, which typically cause UTIs, can enter the urinary tract through the urethra. In the sterile environment of your urinary tract, these bacteria can grow rapidly and develop into an infection.
The urine for a urine culture can be collected in several different ways. The most common method for collecting urine is the midstream clean-catch method. For this, you collect your urine in a cup as you urinate. Before you begin this process, a healthcare provider will ask you to wash your hands and then wash your genitalia several times with a cleanser. Once this step has been completed, you will begin urinating into a sterile cup. The cup is then given to your healthcare provider.
A urine sample can also be collected with a urinary collection bag. This method is used most commonly with children and infants. In some cases, a healthcare provider needs to collect a urine sample with acatheter. To do this, they insert a thin rubber tube through the urethra and into the bladder.
Results of a urine culture are typically ready in two to three days.