From Medscape Medical News
Zosia Chustecka
September 16, 2010 — New data suggest that a 1-time prostate-specific antigen (PSA) test at age 60 can pinpoint men who are likely to die from prostate cancer.
The results, published online September 14 in BMJ, come from a Swedish study with a 25-year follow-up.
The finding "needs to be validated in additional studies," according to an accompanying editorial. The researchers agree there is a need for replication by an independent team; nevertheless, they are enthusiastic about their results.
"This is a key finding," said lead research Andrew Vickers, PhD, from the Department of Epidemiology and Biostatistics at the Memorial Sloan-Kettering Cancer Center in New York City.
"We know that screening detects many prostate cancers that are not harmful, leading to anxiety and unnecessary treatment," he said in a statement. Indeed, a separate study published online September 14 in BMJ found no support for routine PSA screening in all men.
The approach the study authors propose — of testing once at age 60 — pinpoints men who are at increased risk for "really aggressive cancers, the sort likely to lead to symptoms or shorten a man's life," Dr. Vickers said. His team found that most of the deaths from prostate cancer were among the 25% or so of men who had, at age 60, PSA levels higher than 2 ng/mL.
The team originally started their study with the hope of finding a new biomarker for prostate cancer. "What we found instead was a new way of using an old test," Dr. Vickers said.
New Way of Thinking About the PSA Test
In an interview with Medscape Medical News, Dr. Vickers suggested that the finding provided "a new way of thinking about the PSA test that offers clear recommendations for clinical practice."
"We were surprised by just how strong the associations were," he said.
Instead of routine PSA screening for all men, which has led to overdiagnosis and overtreatment, this study suggests that repeat screening can be confined to the 25% or so of men whose PSA level is above 2 ng/mL at age 60.
It also suggests that the 50% or so of men with PSA levels below 1 ng/mL at age 60 can be left alone, and need not have any further PSA screening. "The harms of further screening will probably outweigh the benefits in this group," he said.
This conclusion about discontinuing screening in men with low baseline PSA levels echoes the conclusion of another study published this week.
"We haven't totally solved the problem of overdiagnosis," Dr. Vickers explained. Many patients who have a higher than average PSA at age 60 will develop prostate cancers that are unlikely to lead to death. "Nonetheless, it is clear that risk-stratifying screening will reduce overdiagnosis in men at low risk of prostate cancer death and will improve compliance with screening in those men with most to benefit," he added.
It's certainly thought-provoking.
"It's certainly thought-provoking," was the reaction of Brantley Thrasher, MD, FACS, professor of urology at the University of Kansas in Kansas City, who acts as a spokesperson for the American Urological Association.
However, he cautioned against relying too much on a single 1-off measurement of PSA, because it represents just a "snapshot in time."
PSA is a "continuous variable," and it is important to have a number of data points, he said. "Another concern I have is that there is no PSA below which you can tell a man that he doesn't have cancer," he added.
Dr. Thrasher said he could not agree with the proposal that a man could be told not to worry about prostate cancer ever again on the basis of just 1 test, but he could foresee extending the time period between checks — for example, from having a PSA test yearly to having it every 5 years.
This view was echoed by Andrew Wolf, MD, associate professor of medicine at the University of Virginia School of Medicine in Charlottesville, who was also approached for independent comment by Medscape Medical News. "I don't think you can make a dichotomous decision to continue to screen or not on the basis of 1 test," he said. "In particular, I don't think you can leap to the conclusion that you are good for life if your level is below 1 ng/mL ."
"It would be premature to change our practice on the basis of these findings," he added. But the study is "intriguing" and it does add to the literature. It also adds fuel to the ongoing discussions about extending intervals between PSA tests, he said. Initially, in the United States, this was seen as an annual test, but there is a move toward longer intervals now, especially in low-risk men. The American Cancer Society recently recommended testing every 2 years for men with a PSA value below 2.5 ng/mL, he noted.
One-Time Test Predicts Mortality
The study involved reanalyzing blood samples that had been collected more than 25 years previously for the Malmö Preventive Project. Originally, these blood samples were collected from 60-year-old Swedish men for cardiovascular studies. But Dr. Vickers and colleagues, including senior author Hans Lilja, MD, PhD, also from Sloan-Kettering, analyzed the stored blood samples for PSA.
They collected this information for 1167 men.
Then they scoured the Swedish Cancer Registry for details of men who had been diagnosed with prostate cancer (n = 126), and identified 43 men who developed prostate cancer metastases and 35 who died from the disease.
Conditional logistic regression analysis showed that it was the men with the highest levels of PSA in their blood at age 60 who were most likely to die from prostate cancer.
"As an example, men with a [PSA] concentration ≥ 2 ng/mL at age 60, have, on average, 26 times the odds of dying from prostate cancer than men with a concentration <2 ng/mL," the researchers write.
It was rare to find prostate cancer metastases or death from prostate cancer among men who had a PSA concentration below 1 ng/mL at age 60, the researchers note, but the risk rose rapidly as the concentrations increased.
Risk Stratification
Men aged 60 with a PSA concentration below 1 ng/mL (about half of the men in this study) should be considered at low risk for prostate cancer death and might not need to be screened in the future, the researchers suggest. They might go on to develop prostate cancer, but "even if they do harbor cancer, it is unlikely to become apparent during their lifetime and even less likely to become life-threatening," they add.
In contrast, men with a PSA concentration above 2 ng/mL (about 25% of men in this study) should be considered at increased risk for aggressive prostate cancer and should continue to be screened regularly, they conclude.
But the raised PSA level is "far from being an inevitable harbinger of advanced prostate cancer," they point out. Even among the highest levels of PSA (5.2 ng/mL), only 1 in 6 men will die of prostate cancer by age 85.
Limiting screening to a 1-time PSA test is "likely to shift the ratio of harms to benefits," the researchers note. They argue that it would also "lead to increased acceptance of screening among patients."
In addition, it could increase the uptake of chemoprevention with drugs like finasteride, they suggest. Currently, few men take up this option, but they might be more willing to do so if they were identified as being at high risk.
The researchers wonder whether these results can be replicated by an independent group, and whether the risk stratification would be similar in other populations. This study involved white Swedish men, but the incidence of prostate cancer is lower in Asian and higher in African American people than in white people.
This point was also raised by Dr. Wolf, who pointed out that the study was conducted in one town in Sweden, where the men are likely to be genetically similar, and that they were all 60 years old. Hence, these findings cannot be extrapolated to other populations or other age groups, he cautioned.
Another prostate cancer researcher, Lars Holmberg PhD, MD, from the Division of Cancer Studies at King's College Medical School in London, United Kingdom, said the study is "well done by a very competent group and on good quality data."
The strategy . . . may diminish testing and anxiety and unnecessary diagnoses.
"Everything that can be done to help use PSA testing in a more rational way, minimizing the side effects of testing on wide indications, is worthwhile," Dr. Holmberg told Medscape Medical News.
"The strategy they propose may diminish testing and anxiety and unnecessary diagnoses," he said. However, "it is unclear how much their proposed limitation of PSA use would really affect the major (and very serious!) problem with screening — overdiagnosis."
The study was funded by grants from the National Cancer Institute, the Swedish Cancer Society, the Swedish Research Council, and several other foundations. Dr. Lilja reports holding a patent for free PSA and hK2 assays.
BMJ. Published online September 14, 2010.
Zosia Chustecka has disclosed no relevant financial relationships.
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