PSA Screening

Overview

PSA is a serine protease member of the human kallikrein family. It is produced in both normal and cancerous prostate tissue and secreted into seminal fluid. Its physiologic function is to liquefy semen from its gel form. Normal prostate architecture keeps PSA confined to the gland, and only a small portion is leaked into the circulation. PSA circulates in free and complexed forms. Free forms represent 5%-35% of total PSA. Complexed forms (65%-95%) are bound to protease inhibitors. Binding inactive protease and PSA in the blood has no catalytic activity.

Serum PSA elevations occur as a result of disruptions in the prostate architecture that allow PSA to enter the circulation. This can occur in disease settings (PC [Prostate Cancer], BPH [Benign Prostatic Hyperplasia], or prostatitis [inflammation of the prostate]) or after prostate manipulation (massage, biopsy, or transurethral resection). Increased levels in PC patients cannot be explained by increased synthesis. In fact, PSA expression is slightly decreased in cancer tissue. A prostate-specific antigen (PSA) test measures the amount of prostate-specific antigen in the blood.

WHY IT IS DONE

The prostate-specific antigen (PSA) test is done to:

• Screen men for prostate cancer, which after lung cancer, the most common malignant disease diagnosed in the male population. Since other common medical conditions, such as benign prostatic hyperplasia (BPH) and prostatitis, can cause high PSA levels, a prostate biopsy may be done if your doctor is concerned about signs of prostate cancer.
• Check if cancer may be present when results from other tests, such as a digital rectal exam, are not normal. A PSA test does not diagnose cancer, but it can be used along with other tests to determine if cancer is present.
• Watch prostate cancer during active surveillance or other treatment. If PSA levels increase, the cancer may be growing or spreading. PSA is usually not present in a man who has had his prostate gland removed. A PSA level that rises after prostate removal may mean the cancer has returned or has spread.

Before the Test

Before you have a prostate-specific antigen (PSA), tell your doctor if you have had a:

• Test to look at your bladder (cystoscopy) in the past several weeks.
• Prostate needle biopsy or prostate surgery in the past several weeks.
• Digital rectal exam in the past several weeks.
• Prostate infection (prostatitis) or an urinary tract infection (UTI) that has not gone away.
• Tube (catheter) inserted into your bladder recently to drain urine.

Do not ejaculate for 48 hours before your PSA blood test, either during sex or masturbation. Do not exercise heavily 48 hours before the test.

What causes a raised prostate specific antigen (PSA) level?

A raised PSA level may mean you have prostate cancer but about two out of three men with a raised PSA level will not have prostate cancer.

Other conditions may also cause a raised PSA level, including:

• Inability to pass urine, causing an enlarged bladder (acute retention of urine).
• Enlargement of the prostate that is non-cancerous (benign).
• Older age.
• Urine infection.
• Acute prostatitis.
• Transurethral resection of the prostate (TURP) operation. TURP is an operation used to remove the prostate if you have benign enlargement of the prostate.
• If you have a tube (catheter) to help pass urine

HOW PSA TEST IS DONE?

The health professional taking a sample of your blood will:

• Wrap an elastic band around your upper arm to stop the flow of blood. This makes the veins below the band larger so it is easier to put a needle into the vein.
• Clean the needle site with alcohol.
• Put the needle into the vein. More than one needle stick may be needed.
• Attach a tube to the needle to fill it with blood.
• Remove the band from your arm when enough blood is collected.
• Put a gauze pad or cotton ball over the needle site as the needle is removed.
• Put pressure on the site and then a bandage.

PSA is measured by a simple blood test that does not require fasting or special preparation. Since the amount of PSA in the blood is very low, detection of it requires a very sensitive type of technology (monoclonal antibody technique). The PSA protein can exist in the blood by itself (known as free PSA) or be bound with other substances (known as bound or complexed PSA). PSA is mostly bound to three substances: alpha-2-macroglobulin, alpha 1-antichymotrypsin (ACT), and albumin. Total PSA is the sum of the free and the bound forms. The total PSA is what is measured with the standard PSA test. More recently, a precursor of PSA, proenzyme PSA ([-2] proenzyme PSA), has been identified, which may be helpful in determining prostate cancer risk in men with a PSA under 10 and a normal digital rectal examination. The prostate health index (PHI) is a new approved test that measures the total PSA, free PSA, and [-2] proenzyme PSA.

What’s the Normal Range?

The normal range changes as you get older.

The higher the level of prostate specific antigen (PSA), the more likely it is to be a sign of cancer.

Variations of the PSA test

Your doctor might use other ways of interpreting PSA results before deciding whether to order a biopsy to test for cancerous tissue. These other methods are intended to improve the accuracy of the PSA test as a screening tool.

Researchers continue to investigate variations of the PSA test to determine whether they provide a measurable benefit.

Variations of the PSA test include:

• PSA velocity. PSA velocity is the change in PSA levels over time. A rapid rise in PSA may indicate the presence of cancer or an aggressive form of cancer. However, recent studies have cast doubt on the value of PSA velocity in predicting a finding of prostate cancer from biopsy.
• Percentage of free PSA. PSA circulates in the blood in two forms — either attached to certain blood proteins or unattached (free). If you have a high PSA level but a low percentage of free PSA, it may be more likely that you have prostate cancer.
• PSA density. Prostate cancers can produce more PSA per volume of tissue than benign prostate conditions can. PSA density measurements adjust PSA values for prostate volume. Measuring PSA density generally requires an MRI or transrectal ultrasound.

PSA Density?

Although PSA expression is higher in men with BPH, prostate cancer tissue releases more PSA into circulation. Volume-based prostate parameters have been evaluated to better interpret PSA levels in men with large prostates.

Patients with BPH have transition zone (TZ) enlargement; most prostate cancers arise in the peripheral zone (PZ). Adjusting PSA to account for TZ volume has been evaluated as a method of distinguishing PC from BPH. Thresholds of 0.23 and 0.38 ng/mL/cm3 were proposed for TZ volumes above 20 cc and below 20 cc, respectively.

PSA density (PSAD) is the serum PSA level divided by prostate volume as assessed by transrectal ultrasound. A direct relationship between PSAD and the risk of cancer is also reported. PSAD cutpoints between 0.10 and 0.18 ng/mL/cc were proposed as the levels that should prompt prostate biopsy. However, using 0.15 ng/mL/cc as the cutoff, half of the cancers detected in men with PSA between 4.0 and 10.0 ng/mL would have been missed. Lower cutpoints appear to maximize sensitivity and specificity. PSAD has also been associated with tumor aggressiveness and treatment outcomes.

PSAD is not widely used, as it is an uncomfortable, invasive method requiring skillful performance of transrectal ultra-sonography in which accuracy is influenced by the shape of the prostate. Furthermore, it is more time consuming and expensive than a simple blood test.

WHAT ARE THE RISKS ASSOCIATED WITH THE PSA TEST?

There is very little chance of a problem from having a blood sample taken from a vein.

• You may get a small bruise at the site. You can lower the chance of bruising by keeping pressure on the site for several minutes.
• In rare cases, the vein may become swollen after the blood sample is taken. This problem is called phlebitis. A warm compress can be used several times a day to treat this.
• Ongoing bleeding can be a problem for people with bleeding disorders. Aspirin, warfarin (Coumadin), and other blood-thinning medicines can make bleeding more likely. If you have bleeding or clotting problems, or if you take blood-thinning medicine, tell your doctor before your blood sample is taken.

Medications commonly taken to treat benign enlargement of the prostate (BPH) such as finasteride (Proscar), dutasteride(Avodart), and a combination of dutasteride and tamsulosin (Jalyn) can decrease the PSA by about 50% within six to 12 months of starting their use. Another medication used to treat fungal infections, ketoconazole, can also lower PSA levels. Lastly, herbal supplements such as saw palmetto and those containing phytoestrogens, which are plant-derived chemicals with estrogen-like effects, can also lower the PSA level. It is important to tell your health care provider all the medications, both prescription and nonprescription, as well as any herbal preparations or health supplements that you are taking.

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