'Should I Have a PSA Test?' - Man to Man - Harvard Commentaries

Prostate cancer is common. About 220,000 American men are diagnosed each year. Most of these cases are diagnosed by the inexpensive, safe prostate specific antigen (PSA) blood test. But doctors don't know if that's a good thing or not. The PSA test is one of the most important issues in men's health. It's also the most controversial.

At about age 50, every man will have to decide whether or not to have the blood test. At first glance, screening for prostate cancer seems like a no-brainer: It can be treated and cured; less than 15% of all men with prostate cancer die from the disease. Logic says early treatment should improve survival.

But it's not that simple. The test isn't perfect, the disease has a variable and unusual course, and treatment has potentially troublesome side effects as well as potentially major benefits. Here are the facts to help you decide if the test is right for you.

PSA is a simple protein produced by the prostate gland — both normal and cancerous prostates. The prostate secretes PSA in the ejaculate, where its job is to liquefy semen. This allows sperm to swim toward their target. Some PSA spills into the blood, where it can be measured by a simple blood test. Blood tests can also measure how much of the PSA is bound to other proteins and how much is unbound, or "free."

For a test to be useful, your doctor should be able to tell you whether your result is normal. Most tests have a well-established range of normal values. But for the PSA even this is controversial.

Most doctors use 4.0 ng/ml (nanograms per milliliters) as a cutoff. Lower values are considered normal and higher values are considered abnormal. But since PSA values tend to rise with age, even in healthy men, other experts have proposed a range of normal values that take age into consideration:

The PSA's strengths and weaknesses become clear when it comes to interpreting test results. The test is very good at detecting prostate cancer in its earliest, most curable stages.

In round numbers, PSA testing has the potential to detect about 80% of prostate cancers. Still, a normal or low reading does not rule out the disease: About 20% of men with prostate cancer have "normal" PSA results. But there is no true threshold for normal. For example, a major 2004 study reported that many men with PSA values below 4.0 have prostate cancer.

(Source: Thompson, et al. New England Journal of Medicine, 2004, Vol. 350, pp. 2239-2246.)

Low PSA results cannot rule out prostate cancer, and high results cannot establish the diagnosis. In all, about 70% of men with high PSA results do not have cancer. PSA levels rise with age in healthy men, and conditions, such as benign prostatic hyperplasia (BPH) and prostatitis, can raise it substantially.

Researchers are working hard to improve the accuracy of the PSA test. For example:

Using yearly PSA test results to measure PSA velocity — how much the value changes over time – Researchers suggest that a rise of more than 0.75 ng/ml over the course of a year increases the likelihood of cancer.

Measuring both the total and the free PSA – Cancer is more likely when the free PSA (the PSA that circulates free in the blood without being bound to carrier proteins) makes up less than 25% of the total PSA; the lower the percentage of free PSA, the more likely the diagnosis of cancer.

These experimental refinements may help your doctor interpret your PSA result, but he should also consider other factors that can affect the test.

Finasteride (Proscar) and dutasteride (Avodart), drugs used for BPH, will lower the PSA by about half.

BPH itself will raise from the PSA. Prostatitis, an inflammation of the gland, can send it soaring.

Ejaculation may temporarily bump up the PSA slightly. So men shouldn't ejaculate for 48 hours before the test, particularly if they are being retested to check an abnormal result.

Although new research has cast doubt on the old theory that a digital rectal exam can boost the PSA, many doctors prefer to have the blood test done before they do the exam.

The PSA test can vary up or down without apparent cause. In one major study, about 30% of men with an abnormal PSA result had a normal result on retesting. As a result, the first response to an abnormal result should usually be a second test.

Prostate cancer is a highly variable disease. Many prostate cancers grow slowly. Some remain inactive. On the other hand, some are aggressive and deadly. Unfortunately, the PSA can't discriminate between the harmless and the aggressive cancers. In fact, there is no entirely accurate way to tell the difference. Researchers are developing genetic tests that may help, but the best method we have for now depends on a pathologist looking at a sample of tissue from a biopsy.

Proponents of the PSA point out that the number of prostate cancer deaths in the United States has declined since the test became popular in the early 1990s. But opponents say that the death rate has declined at a similar, though slower, rate in England and Wales, where testing is uncommon.

Randomized clinical trials are the only way to find out if testing saves lives. Large studies are under way in Europe (the ERSPC Trial) and the U.S. (the PLCO and PIVOT Trials), but they will take years to complete. Until then, the only honest answer to the big question is "maybe."

The PSA blood test itself is entirely safe. But an abnormal test result usually leads to a prostate biopsy, which is frightening and uncomfortable. But serious side effects are uncommon.

If a biopsy reveals cancer, it usually leads to treatments that often have side effect, such as impotence and urinary incontinence. There can also be other physical and psychological side effects. Most men would gladly trade potency and even continence for life, but it's not that simple. If treatment saves lives, the PSA test has done much more good than harm. But if men would live as long with no treatment or late treatment, the simple blood test will have done more harm than good.

With all this uncertainty, it's no surprise that even the experts are divided about the value of routine PSA testing.

The American Cancer Society (ACS), the American Urological Association (AUA) and the American College of Radiology (ACR) recommend that doctors offer annual PSA testing to every man above the age of 50. They also call for yearly testing to start at age (AUA) or 45 (ACS) for men at increased risk, such as African Americans and men with family histories of prostate cancer. The ACS says that if a man cannot decide, his doctor should recommend testing.

The Canadian Task Force on the Periodic Health Examination and the Canadian Urological Association recommend against PSA testing in men who seem healthy. The U.S. Preventive Services Task Force concludes: "Although the potential harms of screening for prostate cancer can be established, the presence or magnitude of potential benefits cannot." The American College of Physicians and American Academy of Family Physicians agree that men should be counseled about "the known risks and uncertain benefits of screening for prostate cancer" before they undergo any testing.

The U.S. Office of Technology Assessment said it best: "An informed and reasonable patient could equally well decide to have screening or forgo it." You are the only one who can decide if a PSA test is right for you since to get screened or skip it could be equally valid options." Here is a summary of the four main facts you'll need to make a decision.

Prostate cancer is common. Unlike most malignancies, its growth and natural history are highly variable; it may be aggressive and lethal, but it's more likely to do nothing.

The PSA is the best way to detect prostate cancer in its early, potentially curable stages.

PSA testing has false-negative and false-positive results. There is a good chance that annual testing will lead to invasive testing that will not detect cancer.

The early diagnosis and aggressive treatment of prostate cancer may save lives but can also have substantial adverse side effects. The benefits of PSA screening and aggressive treatment have not been proven in terms of saving lives. If screening has value, it is likely to diminish after ages 70 to 75 and is less likely to help men who have serious medical conditions that reduce life expectancy to 10 years or less.

Harvey B. Simon, M.D. is an Associate Professor of Medicine at Harvard Medical School and a member of the Health Sciences Technology Faculty at Massachusetts Institute of Technology. He is the founding editor of the Harvard Men's Health Watch newsletter and author of six consumer health books, including The Harvard Medical School Guide to Men's Health (Simon and Schuster, 2002) and The No Sweat Exercise Plan, Lose Weight, Get Healthy and Live Longer (McGraw-Hill, 2006). Dr. Simon practices at the Massachusetts General Hospital; he received the London Prize for Excellence in Teaching from Harvard and MIT.