A Test You Shouldn't Jump At

It turns out that there is a large reservoir of unsuspected prostate cancer. In some studies, more than half of men over age 60 have some pathological evidence of the disease. With the advent of PSA (prostate-specific antigen) screening, we are beginning to tap this reservoir and are now undoubtedly detecting and treating some men for "cancers" that would never have caused them problems during their life span. In short, many more men are being told they have prostate cancer and are being treated for a disease that would never kill them or even make them symptomatic.

The NEJM study shows that this genetic test won't fix the overdiagnosis problem.

In the study, some of the men with prostate cancer had very aggressive cancers; others had slow-growing cancers. But the genetic variants could not distinguish between the two. Nor could they predict which patients would develop prostate cancer at a young age or tell which patients already had cancers that had spread beyond the prostate. They could not predict the Gleason score (the pathologist's measure of how aggressive cells look under the microscope) or the PSA level (the biochemical measure of cancer aggressiveness). The variants did not even distinguish between those who had a family history of prostate cancer and those who did not (surprisingly, since one would expect this information to be contained in the genome).

In other words, while the test seemed to help predict the risk of getting prostate cancer, it didn't seem to help predict who would get a bad prostate cancer -- one that might kill you.

Does the risk information help?

It is perfectly plausible that a subsequent study will identify a set of genetic variants that will predict prostate cancer death. Imagine this was the study that did it.

Some men would be told their risk of prostate cancer death had doubled; others would be told their risk was cut in half. But the most common test results would be smaller changes in risk (for example, a risk that is 13 percent higher or, say, 23 percent lower than the risk of the average man). You would want to ground this information with the absolute risk of prostate cancer death -- which is roughly 3 percent over a lifetime.

So, you could learn that your risk of prostate cancer death over a lifetime was either 1.5 percent, 2.3 percent, 3 percent, 3.2 percent or 6.8 percent. You might also want to consider the competing risk of dying from something other than prostate cancer. That would still be more than 90 percent, no matter what your test result is.

Imagine you were a man in his 40s getting these results. What would you do differently? Would a lifetime risk of 6.8 percent be high enough to warrant a prophylactic prostatectomy? Certainly not for most of us.

Would you start hormonal therapy? Probably not, given the side effects of impotence, hot flashes, osteoporosis and heart disease. So that leaves you with looking for the disease early, through more regular PSA screening. The truth is we don't know whether PSA screening can help lower the death rate from prostate cancer.

If you believe it can, as many men and doctors do, wouldn't you continue to be tested regardless of whether your risk was 6.8 percent, 1.5 percent or anywhere in between? And if you are not a believer and are worried about the overdiagnosis and overtreatment initiated by PSA screening, would changes in your risk change your mind about screening?

You have to decide whether this test is viable or not. But you need to be ready for this new world of genetic testing. It's a world filled with tests that might show relatively small changes in risk -- a slightly higher risk of one cancer, a slightly lower risk of another, perhaps with other small changes in the risk of heart disease, diabetes, etc.

Exactly what we are predicting is not always clear. And what to do about what we find is even less so.

H. Gilbert Welch is a general internist at the Veterans Affairs Medical Center in White River Junction, Vt., and a professor at the Dartmouth Institute for Health Policy & Clinical Practice in Hanover, N.H. He is the author of "Should I Be Tested for Cancer?" (UC Press).