The pros and cons of PSA screening

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A prostate-specific antigen (PSA) blood test measures the level of a protein called prostate-specific antigen (PSA), which is made by cells in the prostate. Doctors use the test to detect prostate cancer. Since its introduction in the late 1980s, the prostate-specific antigen (PSA) test has been hailed as a way to detect prostate cancer in its earliest, most curable stage. It has been called one of the most important tests a man can have. So why are many experts now stepping back, and even discouraging the use of widespread PSA screening?

Concerns about PSA screening

The shift comes on the heels of a growing body of evidence that shows the benefits of PSA screening may not outweigh the potential harm of unnecessary treatment. PSA screening has always been somewhat controversial. That's because PSA tests often alert doctors to the presence of cancer, but there is no precise way to determine, definitively, whether the cancers detected would have ever caused symptoms or harm during a man's lifetime. One study estimated overdetection to rise with age, from 27% at age 55 to 56% by age 75.

Despite this, to be on the safe side, most men with elevated PSA levels will opt for treatment, frequently suffering side effects such as incontinence and impotence. Increasingly, there are questions about the effectiveness of PSA screening for prostate cancer. Just how many lives are actually being saved? And is the emotional and physical toll on the millions of men who are being overdiagnosed and overtreated worth it?

What the research says

Two long-awaited studies—one conducted in the United States and the other in Europe—were supposed to help settle the debate over the value of PSA testing. Instead, the trials, published in the New England Journal of Medicine in March 2009, seemed to come to opposite conclusions. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial reported no survival benefit with PSA screening and digital rectal examination, but the European Randomized Study of Screening for Prostate Cancer (ERSPC) found a 20% reduction in prostate cancer deaths. The ERSPC study estimated that for every life saved, 48 men are treated and 1,068 men are screened.

Although experts are somewhat split on the value of PSA tests as a screening tool, there is widespread agreement on two major points: overdiagnosis and overtreatment rates are far too high, and there is an urgent need to refine PSA testing to be a more effective screening tool. The principal investigator of the Prostate Cancer Prevention Trial and his colleagues wrote an editorial in The Journal of the American Medical Association in October 2009 that took a closer look at the issues. They pointed out that while the amount of prostate cancer diagnosed has risen dramatically since PSA testing began, there has not been a proportional decrease in the number of men with metastatic tumors. It appears screening may be detecting a disproportionate number of lower-risk cancers, while missing many of the most aggressive tumors, which may advance too rapidly to be found with periodic testing.

The debate over the effectiveness of PSA screening has quickly filtered into the offices of general practitioners and urologists. On a daily basis, confused men are asking their doctors: "Should I have a PSA test or not?"

What you should know about PSA screening

  • Screening doesn't lower your risk of having prostate cancer; it increases the chance you'll find out you have it.
  • PSA testing can detect early-stage cancers that a digital rectal examination (DRE) would miss.
  • A "normal" PSA level of 4 ng/ml or below doesn't guarantee that you are cancer-free; in about 15% of men with a PSA below 4 ng/ml, a biopsy will reveal prostate cancer.
  • A high PSA level may prompt you to seek treatment, resulting in possible urinary and sexual side effects.
  • Conditions other than cancer—BPH and prostatitis, for example—can elevate your PSA level.

In the past few years, more and more men who undergo PSA screening and later learn that they have cancer have opted to pursue active surveillance. This strategy involves frequent monitoring of the disease through PSA tests and biopsies—and postponing treatment until the cancer shows signs of increasing its activity. In short, these men choose to live with prostate cancer until it advances, sometimes avoiding potentially life-altering side effects for several years.

PSA testing guidelines from the American Cancer Society emphasize discussing the pros and cons of prostate cancer screening with your doctor, including your individual level of prostate cancer risk, before having a PSA blood test.

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Does hormone therapy cause dementia?

Q. The Women's Health Initiative found that hormone therapy wasn't helpful for avoiding dementia; there was some suggestion that it might even cause cognitive problems. Am I at risk for dementia by continuing hormone therapy?

A. You're right about the results of the Women's Health Initiative Memory Study (WHIMS), the largest clinical trial to date of the effects of hormone therapy (HT) on cognitive function and dementia. Women ages 65 to 79 took HT (estrogen alone or estrogen combined with a progestin) or a placebo. After four to five years, the researchers found that taking HT didn't improve cognitive function. Moreover, the women who took combined estrogen and progestin were twice as likely as the placebo takers to develop dementia.

These findings don't square with animal and laboratory studies suggesting a favorable effect of estrogen on cognitive function. And there's strong biological evidence that estrogen is important for brain function in women. Estrogen receptors are found throughout the brain, and many interactions take place between the brain and the reproductive endocrine system. Some research suggests that ovary removal during hysterectomy increases the risk of cognitive problems, presumably due to the loss of estrogen.

So what accounts for the WHIMS results? Some researchers think the problem is in the timing; they suggest that HT is more likely to benefit the brain if it's started in early menopause. A five-year clinical trial called the Kronos Early Estrogen Prevention Study (KEEPS) is now addressing this question. Results are expected in 2011.

Based on what we know right now, HT won't improve your thinking or stave off dementia. But could it increase your risk for cognitive problems? Here the evidence is less compelling. We do know that taking HT increases the risk for several serious conditions, including blood clots, stroke, heart attack, and breast cancer (when estrogen is combined with a progestin). Unless you have burdensome hot flashes or vaginal atrophy that can't be controlled any other way, I suggest that you taper off HT, which is recommended only for the short-term relief of such symptoms. There are several non-hormonal, risk-free strategies that may help your memory and thinking, including these: get regular exercise; keep learning — through work, hobbies, or pursuits such as reading; get enough sleep; and review your medications, to make sure you're not taking anything that could interfere with your thinking.

— Celeste Robb-Nicholson, M.D.
Editor in Chief, Harvard Women's Health Watch