From Our 2008 Archives

Earlier Start, Stop for PSA Testing?

Prostate Cancer Screening May Start Earlier — and Stop Sooner

By Daniel J. DeNoon
WebMD Health News

Reviewed By Louise Chang, MD

May 22, 2008 — Prostate cancer screening may start earlier in life — and, for some lucky men, end sooner.

Two of the hottest controversies in PSA prostate cancer screening are the ongoing debates over when a man should start screening and when he should stop.

These are life-and-death questions. If he starts screening too late or stops too soon, a man risks dying of undetected prostate cancer. If he starts too soon or ends too early, he risks harm from unnecessary biopsies and treatments.

Two new studies reported at this week's meeting of the American Urological Association in Orlando, Fla., will either help settle these questions or add fuel to the fire.

One study shows that a single PSA test before age 40 can identify men with almost no chance of getting prostate cancer — and men with very high odds of getting prostate cancer — in the next 30 years.

Another study shows that if a man reaches age 75 with a very low PSA score (below 3 ng/mL), it's almost a sure bet he'll never die of prostate cancer.

Early PSA Test — and Then No More?

Hans Lilja, MD, PhD, of New York's Memorial Sloan-Kettering Cancer Center, isn't totally disinterested in PSA testing. He holds patents for blood tests for free PSA and other prostate-cancer-related assays.

But Lilja's provocative title for his AUA presentation was "A single PSA predicts prostate cancer up to 30 years subsequently, even in men aged less than 40."

PSA is prostate-specific antigen. It's a molecule given off by all cells of the prostate gland. The normal prostate sheds PSA. It sheds even more PSA during a prostate infection. But PSA usually goes way up when a man has prostate cancer.

Lilja and colleagues have three hypotheses about PSA. The first is the widely held idea that whatever causes prostate cancer leads to premalignant changes in prostate cells and results in a rise in PSA. The second is that whatever causes prostate cancer directly leads to a rise in PSA. And their third hypothesis is that a rise in PSA itself is part of the cause of prostate cancer.

In their view, prostate cancer doesn't happen overnight. Instead, Lilja and colleagues see it as a process that begins many years before cancer is diagnosed. And a rise in PSA may signal that this process is under way.

"Our findings are highly important in that they identify this sort of marker signal exists before age 40," Lilja tells WebMD. "It is unique that we have a biomarker with such extensive delay between when a blood sample is drawn and a diagnosis — and are able to associate this marker with disease."

Lilja and colleagues took advantage of a "natural experiment" — 21,277 Swedish men aged 33 to 50 who gave blood from 1974 to 1986 as part of a heart study. PSA screening isn't widespread in Sweden, but cancer registries are. So the researchers were able to tell which men got prostate cancer and which didn't.

In their first look at the data, the researchers found that a single PSA test before age 50 predicted low or high risk of prostate cancer. Now they report that a single PSA test before age 40 predicts prostate cancer risk.

"We are seeing that low PSA values are associated with low future risk of prostate cancer," Lilja says. "The median PSA level in this population of men with low long-term risk is around 0.6 ng/mL."

The researchers hoped to find a time point when the prostate cancer process starts. But that effort has not yet been successful.

"So far we have not been able to see an age where we don't see the signal," Lilja says. "But now we know we can identify individuals who, in the future, are quite unlikely to benefit from further testing and intervention. What that means for PSA screening guidelines is not yet known. And how often a low-risk man will need PSA testing, we don't know."

However, AUA spokesman Ira D. Sharlip, MD, clinical professor of urology at the University of California, San Francisco, says the AUA committee responsible for these guidelines is taking a hard look at the Lilja team's data. Current AUA recommendations call for men to start PSA screening at age 50 if they are not at high risk, because relatively few such men get prostate cancer before then.

"The PSA guideline document that AUA has was written in 2000; it is being updated now," Sharlip tells WebMD. "On the basis of this study, there is a possibility they might revise it to age 40."

Can PSA Screening Stop at 75?

Since prostate cancer takes a while to develop — and even longer to become deadly — there's obviously an age beyond which prostate cancer screening will result in far more risk than benefit. But what's that age?

Sharlip says the rule of thumb is to stop PSA screening when a man's probable life expectancy is less than 10 years.

"With good life expectancy, a man is at risk of prostate cancer and death if he doesn't get his PSA tested," Sharlip says. "But what about a man with rising PSA that's still at a marginal level? That is exactly the situation that is poorly defined."

Help comes from Anna Kettermann and colleagues at Johns Hopkins University. Kettermann and colleagues collected data from 849 men participating in the Baltimore Longitudinal Study of Aging.

Eighteen of the men died of prostate cancer. Not even one had a PSA under 3.0 ng/mL. Moreover, men with PSA levels this low had virtually no chance of serious prostate cancer or PSA levels that later soared.

"We wanted to look for the men who have PSA values that will never bring them to the condition that prostate cancer will kill them," Kettermann tells WebMD. "If a man is old and has a low PSA and a history of low PSA, he is unlikely to develop high-risk disease."

Sharlip warns that the findings are not necessarily dire for elderly men with PSA levels above 3 ng/mL.

"I follow these men carefully, get a PSA test every three months, and if I see the PSA turning up I recommend a biopsy," he says. "In a number of these elderly men I find only low-risk prostate cancer, so I don't treat them — as it turned out, they didn't need the biopsy. But more than occasionally I find intermediate- or high-grade prostate cancer, and those are the men we want to know about."

SOURCES: American Urological Association Annual Meeting, Orlando, Fla., May 17-22, 2008. Ulmert, D. BMC Medicine, published online Feb. 15, 2008; DOI: 10.1186/1741-7015-6-6 (What's this?) Lilja, H. Journal of Clinical Oncology, Feb. 1, 2007; vol 25: pp 431-436. News releases, American Urological Association. Hans Lilja, MD, PhD, attending research clinical chemist, Memorial Sloan-Kettering Cancer Center. Anna Kettermann, statistician, Johns Hopkins University, Baltimore. Ira D. Sharlip, MD, chairman, public media committee, American Urological Association; clinical professor of urology, University of California San Francisco.

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