PSA Test: New Studies, Same Old Questions

March 18, 2009— -- Have you ever wanted something for such a long time that when it finally arrived you found yourself terribly disappointed?

Maybe that's the best way I can summarize my feelings about two studies reported today in the New England Journal of Medicine on the topic of prostate cancer screening and whether it really makes a difference.

For years we have been saying that there wasn't sufficient evidence to prove that screening for prostate cancer saved lives. That was almost always followed by a statement that we were waiting for the results of two trials in the United States and Europe. "They will show us the answer," we said.

In the meantime, millions of men continued to get tested and undergo treatment, even though no one could really say if we were saving lives, or just sending millions more men to unnecessary treatment with all sorts of side effects.

Well, my friends, the waiting is over. The day has arrived. And I don't know that we now have any better idea whether prostate cancer screening actually works.

Common -- But Is It a Concern?

Prostate cancer in the United States in 2008 was estimated to occur in 186,320 men. The American Cancer Society estimated that 28,660 men would die from prostate cancer in the United States in 2008.

Prostate cancer is the most common cancer in men, accounting for 25 percent of cancers diagnosed in men in 2008. It is the second leading cause of cancer death in men -- behind lung cancer -- accounting for 10 percent of cancer deaths. A man in this country has a one in six chance of being diagnosed with prostate cancer during his lifetime, with most of those diagnoses occurring at ages 70 and older.

Importantly, and not mentioned as often, is the fact that only one in 34 men will die of the disease.

The two research papers in the New England Journal of Medicine describe early results from two different trials -- one in the United States and one in Europe -- that were designed to find out whether tests to find prostate cancer early reduced deaths from the disease.

Get Your Questions Answered at the ABCNews.com OnCall+ Prostate Cancer Center

In the United States trial, 76,693 men between the ages of 55 and 74 years were randomly assigned to be screened or receive "usual care" from 1993 to 2001. The men in the screened group had annual PSA testing for six years and digital rectal examinations every year for four years.

The good news is that the men in this trial who were in the screened group did a reasonably good job of following the directions of the trial: 85 percent of them had their PSA blood test, and 86 percent did the rectal exam as requested.

The not so good news is that by the sixth year of the trial, 52 percent of the men in the control group -- who were left to their own devices as to whether they should get the PSA blood test -- had the test. Forty-six percent of these men had a rectal exam.

What that leaves us with is a clinical trial where the men who were asked to get screened did get screened. And of the men who were not told to get screened, about half of them got screened anyway.

The end result was that after seven years of follow-up, there were more cancers diagnosed in the screened group (no surprise there: go looking for prostate cancer in a man and you have a pretty good chance of finding it) compared to the "control group," but the deaths were a bit higher in the screened group compared to the supposed no-screening group.

The conclusion? "After seven to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups."

The authors acknowledged some limitations in their study, including the fact that treatment for prostate cancer may have improved so much as to negate any benefit that screening may have had. They also point out that it may yet be too early to draw a definite answer from the study, and that further follow-up of the men participating in this study may be warranted.

What about the European trial? That one is even more confusing.

In this trial, 182,000 men between the ages of 50 and 74 in seven European countries were randomly assigned to get a PSA test "at an average of once every four years" or to a control group that did not get screened. Of this group, 162,387 were actually part of the current report, and these men were between the ages of 55 and 69 years.

Half the men were followed for more than nine years, and half less than nine years. Eighty-two percent of the men who were offered screening got at least one PSA test. Of those who had at least one PSA test, 8.2 percent were diagnosed with prostate cancer, and of those who did not have the test, 4.8 percent had a diagnosis of prostate cancer made during the period of the study.

The end result was that the risk of death in the men who were screened was 20 percent less than those who were not screened. In more plain terms, according to the authors, "1,410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer."

When one considers all of the problems (urine incontinence, impotence, pain and bleeding among others) associated with treatment for prostate cancer, that is a lot of men left with a lot of symptoms to save one life.

When you dig deeper into the study, you begin to see some inconsistencies that may have influenced the results.

Recruitment and randomization procedures were not the same in every country that participated. Portugal stopped participating, and France joined late. All countries included men ages 55-69, but Sweden also included men who were 50-54. The Netherlands, Italy, Belgium and Spain included men up to the age of 74, and in Switzerland, men were screened up to the age of 75.

In all countries except Finland, men were randomly assigned on a "50-50" chance basis to screening or no screening. Finland decided to screen two men for every one in the control group.

Here is another interesting piece of information: In the European trial, 75.9 percent of the men who underwent prostate biopsy because of a PSA level of 3 or greater did not have prostate cancer.

The conclusion of this study?

"The ratio of benefits to risks that is achievable with more frequently screening or a lower PSA threshold than we used remains unknown," the authors wrote. "Further analyses are needed to determine the optimal screening interval in consideration of the PA value at the first screening and of previously negative results on biopsy."

Sounds like a draw to me.

There was an editorial that accompanied these two articles, which reported that, in the mode of "do as I do," 95 percent of male urologists and 78 percent of primary care physicians who are age 50 or over have had their own PSA tested. The author also noted that there has been a significant decline in deaths from prostate cancer since the early 1990s.

The editorialist goes on to say:

"Neither set of findings seems definitive... (The) decisions to publish now can be criticized as premature, leaving clinicians and patients to deal with the ambiguity.

"The implications of the trade-offs reflected in these data, like beauty, will be in the eye of the beholder... As a result, a shared decision-making approach to PSA screening, as recommended by most guidelines, seems more appropriate than ever."

Shared decision-making about getting a PSA test and digital rectal examination for the early detection of prostate cancer is exactly what the American Cancer Society recommends. You need to talk about prostate cancer screening with your doctor or other health care professional. You need to know the risks, benefits and harms that can occur as a result of screening for prostate cancer before you embark on getting these tests as part of your routine medical care.

Back to the Drawing Board?

What is the impact of these reports?

Unfortunately, now armed with the knowledge I have been waiting for, I am completely underwhelmed.

Our recommendation regarding prostate cancer screening is no different now than what the society has been saying for years. The only difference now is that the long awaited studies have been reported. And our message hasn't changed.

Maybe more men will give some thought as to whether they really want or need a PSA test and rectal examination. I don't think that is a bad thing.

At first blush, my reaction was that these studies don't really give us the answer we were waiting for. But on further reflection, maybe they did -- sort of like not making a decision is, in fact, a decision. Perhaps not getting a clear answer to the question as to the value of prostate cancer screening is, in fact, a clear answer.

At the end of the day, each of us will have to be our own judge on the merits of the case and what we want to do for ourselves when it comes to the early detection of prostate cancer.

Len Lichtenfeld is deputy chief medical officer of the American Cancer Society. You can view the full blog by clicking here.

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