Since its introduction 20 years ago, the prostate-specific antigen (PSA) blood test has become a key tool for screening men for prostate cancer.

Until the PSA test, men received only a digital rectal exam (DRE), in which the doctor inserts a gloved, lubricated finger into the rectum to feel the prostate for lumps and thickenings that suggest a tumor.

The PSA test became popular because it can help detect some prostate cancers earlier than the DRE alone. An elevated PSA level doesn't necessarily mean that cancer is present, but it can indicate the need for a biopsy.

Yet now, after years of use, experts disagree about whether men should receive routine PSA testing. Some medical groups, such as the American Urological Society and the American Cancer Society, advocate annual screening for all men age 50 and older-and starting at age 40 or 45 for men at high risk (African-Americans and men who have a family history of the disease). Other groups, including the American Medical Association, advise doctors to spell out the risks and benefits of PSA testing and let the patients decide. Unfortunately, few men have all the facts about PSA testing. What men need to know...

Interpreting Test Results

PSA is produced by the walnut-sized prostate gland. When cancer is present, the prostate secretes more PSA than usual. But cancer isn't the only reason for increased PSA levels. Infection or the enlargement of the prostate that accompanies aging, known as benign prostatic hyperplasia (BPH), can also raise PSA levels. Even ejaculation within 48 hours of the test can affect PSA. Therefore, PSA levels can be difficult to interpret.

What is a "normal" PSA level? Until the last several years, it was defined as below 4.0 nanograms/milliliter (ng/ml), but newer data on prostate cancer have made it clear that a man's risk often rises at lower PSA levels. Many experts now say that 2.5 or below is normal for men in their 40s...up to 3.5 is normal for men in their 50s. ..up to 4.5 is normal for men in their 60s... and up to 6.5 is normal for men 70 and older. PSA levels naturally rise with age, even in the absence of cancer.

Another way of looking at PSA is by using percentages-one-third of men who have a PSA level between 2 and 4 have prostate cancer 44% have prostate cancer when their PSA level is 4.1 to 7...and one-half have the disease at a PSA level of 7.1 to 10. Above 10, the chance that a man has prostate cancer rises to two-thirds.

What's Wrong With The PSA?

If screening using the PSA test (followed by other tests, such as biopsy, when indicated) catches most cancers-and early detection is generally desirable-why do many experts question whether men should have the PSA test?

The answer is not simple. Most prostate tumors grow very slowly-if at all-and are best left alone because they are unlikely to lead to death. Other prostate cancers need aggressive treatment to keep them from spreading. In these cases, early detection can mean the difference between life and death.

How can you tell the difference? You can't with certainty. That's why a substantial number of prostate cancers will be treated even though they are not life threatening. Treatment generally means surgery to remove the prostate and/or radiation to kill the tumor. These treatments carry significant risks for impotence and urinary incontinence.

Proponents of PSA testing point out that prostate cancer deaths have declined in the years since the test has been widely used. However, PSA skeptics say that this trend could also be the result of better treatment, not just better diagnosis.

Improving Accuracy

In recent years, several variations of the PSA test have been used to improve its accuracy and limit the number of men who are advised to get a biopsy. They are...

Free vs. bound PSA. The majority of PSA floats through the bloodstream bound to protein molecules, while a smaller portion of PSA is free. Evidence has shown that when PSA is produced by cancer, higher levels than usual are in the bound form and a smaller proportion is free. Less free PSA (15% or below) means a greater chance that it's cancer. This test is recommended for men who have abnormal results from the standard PSA test.

PSA velocity. The rate at which PSA changes between three or more annual readings is a significant predictor of cancer. The PSA level should not increase more than 0.75 per year, according to the National Cancer Care Network, a consortium of cancer specialists. The group recommends a biopsy if levels rise faster.

PSA density. The larger a noncancerous prostate, the more PSA it will normally produce. So density-the amount of PSA divided by the size of the gland-may indicate whether prostate cancer is present. High density-that is, a big number in a man who has a small prostate means a greater risk. A range of 0.10 to 0.15 and above indicates increased risk.

Drawback: Measuring the prostate requires rectal ultrasound, a procedure that involves placing a thumb-sized probe into the rectum.

What To Expect From A Biopsy

If your PSA results are abnormal, the next step is a biopsy. Some men get a biopsy as soon as possible, while others wait several months and repeat the PSA test. The second PSA test results are different enough to warrant a third PSA test in less than 20% of cases, but it is often worth waiting and repeating the test.

Important: If your doctor suspects a prostate infection (from a clinical exam and bacterial culture), he/she should prescribe a course of antibiotics before repeating the PSA test.

If a biopsy is indicated, your doctor will refer you to a surgeon, who will perform the procedure.

What the biopsy involves: While you lie on your side, the surgeon inserts an ultrasound probe through your rectum. A needle-like device is guided through a hole in the probe to take tiny prostate tissue samples that will be examined under a microscope. An estimated 40% of surgeons take only six tissue samples, which allows cancer to be missed 30% to 50% of the time. That's why it's crucial for the surgeon to take at least 12 tissue samples, which decreases the false-negative rate to less than 20%.

Important: Injecting local anesthesia into nerves at the base of the prostate makes the procedure less painful. Not all surgeons are familiar with this technique. Before the biopsy, make sure that local anesthesia is available.

Following the biopsy, there may be slight soreness in the area around the rectum for a few days.

The risk for infection from the biopsy is 1%. To minimize this risk, surgeons should give an antibiotic beforehand.

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