JEFFREY BROWN: When is a screening test for cancer beneficial and when might it cause more harm than good? Doctors have been grappling with that for years in the case of prostate cancer, the most common type of cancer among American men and the second deadliest.
Current guidelines from the American Cancer Society and the American Urological Association recommend a screening test be offered to most men over 50. But yesterday a federal task force recommended that doctors should stop routine screenings for men age 75 and older.
To walk us through all this, we’re joined by Dr. Barnett Kramer, associate director for disease prevention at the National Institutes of Health. He’s also involved with a major trial looking at screening for four cancers, including prostate.
Welcome to you.
DR. BARNETT KRAMER, National Institutes of Health: Thank you.
JEFFREY BROWN: Let’s first step back and explain the PSA test that’s under debate here. What does it do? And what are its limitations?
DR. BARNETT KRAMER: The PSA stands for an enzyme that’s called prostate-specific antigen. And the name is very helpful, that is, it is prostate-specific, not prostate-cancer-specific.
So it is secreted from damaged cells in the prostate, whether it’s a malignant condition or benign, and that’s what makes interpretation of the test quite difficult.
JEFFREY BROWN: Meaning what?
DR. BARNETT KRAMER: PSA can be leaks from any cells that are damaged. And that might be simple inflammation as occurs with a condition known as prostatitis, a benign condition. It can also come out of the prostate just with simple benign enlargement, benign prostatic hyperplasia.
The majority of times when the PSA is elevated, in fact, is because of benign conditions rather than prostate cancer.
However, because the level often goes up in the setting of prostate cancer — again due to damaged cells — it can indicate that a man has prostate cancer.
The downside of invasive tests
JEFFREY BROWN: So there has been this longstanding uncertainty over the test that you're describing, but the standard recommended treatments -- not treatment, but, I mean, care -- seems to be to offer it to men over 50, but now this panel comes out and says not for men over 75. Why?
DR. BARNETT KRAMER: Well, because the evidence has not been as clear as we would like to. A variety of organizations actually have come down on different sides of the issue. But it is true that some societies say that it should be offered to all men regardless of age, as long as they've reached the age of 50.
What's important about the recommendation from the United States Preventive Services Task Force guideline that came out today is that they basically say, because we know too little about the benefits and harms, it shouldn't be considered a routine test for all men. For men ages 75 and above, the likelihood of a net harm to doing the test is high and so, therefore, it should not be given to men age 75 and above.
JEFFREY BROWN: Stop there for a moment. What is the possible -- what are the possible harms? What is the downside?
DR. BARNETT KRAMER: The downside are some invasive tests that are triggered by an abnormal PSA in the bloodstream, and that involves multiple needle biopsies of the prostate gland. And the downsides of that range from something relatively straightforward, such as pain from the biopsy, all the way up to hospitalization from bleeding or infection, which occurs in a small number, but a finite number, of men.
The more serious side effects occur once a man has been diagnosed with prostate cancer. And that will trigger radical prostate surgery and/or radiation therapy. And they have a lot of side effects.
Prostate cancer surgery involves a relatively high risk of sexual impotence and also a lower, but still substantial, risk of urinary problems, like loss of urinary control.
Risks may outweigh the benefits
JEFFREY BROWN: If you stay with men over 75 for a moment, is it known what percentage of men over 75 now get the test and how many end up with treatment?
DR. BARNETT KRAMER: Probably more than half of men over the age of 75 have had at least one PSA test. There may have been a leveling of the frequency with which men get prostate cancer because of a growing awareness of the controversy and different recommendations from different organizations. However, I think a good estimate is that more than half of men have been screened for prostate cancer.
JEFFREY BROWN: Now, you said that different organizations have come out on different sides of this. Even today, there were arguments that these guidelines may not be -- may not be the best way to go. If the argument is it saves some lives, why not do the test?
DR. BARNETT KRAMER: Well, any medical intervention has its harms. And so whenever you're considering a medical intervention, you have to weigh the benefits against the harms.
In this case, we don't even know the magnitude of the benefits. As the U.S. Preventive Services Task Force pointed out so well, the benefits are actually theoretical. We do not have evidence in hand to prove that screening prevents deaths from prostate cancer.
So we're weighing theoretical benefits against known and sometimes inescapable harm.
JEFFREY BROWN: No evidence at all? Because I did see a quote from a University of Kansas, Dr. Brantley Thrasher, "We've seen a dramatic drop in mortality."
DR. BARNETT KRAMER: Yes. And so many organizations, including the United States Preventive Services Task Force, do not view that as very strong evidence at all. Many view that as one of the weakest forms of evidence.
And the reason is, it is simply trying to guess reasons for changes in population trends and prostate cancer deaths.
JEFFREY BROWN: In other words, it's not clear that the screening led to the drop in mortality?
DR. BARNETT KRAMER: Exactly. There are many factors that are in common use today that could explain a change in prostate cancer deaths, including advances in therapy.
Over the same era when PSA came into common usage, the use of hormone therapy to treat prostate cancer was also becoming more common. And a number of trials have clearly shown that hormones can decrease the risk of dying of prostate cancer. And, therefore, trying to separate the effects of the treatment from the effects of screening is particularly difficult.
Learning more about the risks
JEFFREY BROWN: Now, you said that some of the same calculations clearly go into for men under the age of 75, from 50 to 75. So what is the take-home message here? What should men be doing?
DR. BARNETT KRAMER: I think the message that -- I'll call it the USPSTF -- gives is particularly clear for men 75 and above, and that is, it is likely that the harms outweigh the benefits and it should not be used as a routine test at all. They give it a Grade D recommendation, which is their strongest recommendation against doing a routine test.
For men under the age of 75, the message is more nuanced because of the evidence isn't quite as clear. That's where they say PSA should not be treated as though it is a routine test to be taken by all men irrespective of age.
It is a test that should be discussed in detail. And men should be made well aware of what we know and what we don't know, not just what we hope is true.
JEFFREY BROWN: Are there higher risks -- there are higher risk groups. I've read African-Americans, for example. So is there a way to individualize this, in some sense, where you can go to your doctor and say, "Here's family history or here's some kind of history to determine in the future what should be done"?
DR. BARNETT KRAMER: That's a important question, because it affects so many men in our country. And the USPSTF took that on head-on. They concluded that, despite the fact that African-Americans do have a higher risk, still not enough is known about the balance of risks and benefits of screening to offer it to them and perform the test routinely, again, without a very detailed discussion.
JEFFREY BROWN: All right, in the meantime, the test continues -- the trials continue?
DR. BARNETT KRAMER: The trials continue. And we hope that that will fill in the very important gaps of knowledge. And that's why I'm so committed myself to a trial which is being conducted by the National Cancer Institute, a component of the National Institutes of Health.
JEFFREY BROWN: All right, Dr. Barnett Kramer, thank you very much.
DR. BARNETT KRAMER: Thank you.