Three PSA Tests Over Lifetime Sufficient for Many Men

Zosia Chustecka

April 18, 2013

Instead of routine prostate-specific antigen (PSA) screening — which has come under criticism in recent years amid concerns that it leads to overdiagnosis and overtreatment — just 3 PSA tests over the course of a lifetime is sufficient for many men.

This premise comes from a team led by Andrew Vickers, PhD, from the Memorial Sloan-Kettering Cancer Center in New York City, in collaboration with teams at the University of Washington in Seattle and Skåne University Hospital in Malmö, Sweden.

However, this proposal from a single, unvalidated study is not ready yet for clinical use, and the study should be considered hypothesis generating, say experts.

Simple Algorithm

In 2010, Dr. Vickers' team reported that a single PSA test at the 60 years of age is all that is needed for many men. That conclusion was criticized as being rather simplistic, because a single PSA test is just a "snapshot in time," whereas PSA is a "continuous variable" and it is important to have a number of data points, Brantley Thrasher, MD, FACS, professor of urology at the University of Kansas in Kansas City, said at the time.

In an extension of that 2010 work, Dr. Vickers and colleagues offer a simple algorithm for prostate screening in a study published online April 16 in BMJ. For at least half of all men, it would mean only 3 PSA tests during their lifetime.

In their proposed strategy, all men with a reasonable life expectancy would be invited for PSA screening in their mid to late 40s.

The best age for this initial PSA test is around 45 years, unless there is a strong family history of prostate cancer. Age 40 might be too early, and age 50 might be too late to identify a man's risk of developing an aggressive cancer, Dr. Vickers explained in a statement. "The big take-home message is that a single PSA test at age 45 can be used to predict a man's long-term risk of developing an aggressive prostate cancer," he noted.

Men who were found to have a PSA level below 1 ug/L on the initial test would be advised to return for screening in their early 50s and again at age 60. At the age of 60, men who still had a PSA level below 1 ug/L would be exempt from further screening.

Given existing data, these 3 PSA tests (mid to late 40s, early 50s, and 60) "are probably sufficient for at least half of men," the team concludes.

However, men who are found to have a PSA level of 1 ug/L or higher on the initial test are at above-average risk of developing life-threatening prostate cancer. These men should regularly undergo screening until around age 70. The literature suggests repeating the PSA test every 2 or 4 years, the researchers write.

For men 40 to 55 years, those with PSA levels in the top 10% of this age group should receive particular focus. This group contributes to close to half of all deaths from prostate cancer that occur before the age of 70 to 75, they add.

Such a risk-stratified approach to PSA screening will improve the ratio of its benefits and harms, the researchers note.

Based on Malmö Data

This study, like the 2010 one, is based on data collected during the Malmö Preventive Project, which involved 21,277 men 27 to 52 years of age. Blood samples taken at baseline and 6 years later were analyzed for PSA concentrations. The health records of these men were then linked to the cancer registry at the National Board of Health and Welfare in Sweden, and a search found that 1369 had developed prostate cancer. Among these, there were 241 cases of metastases and 162 deaths from prostate cancer.

The researchers used a nested case–control design; controls and cases were matched for the index event (prostate cancer diagnosis), as were the end points of metastasis and death.

They then estimated absolute risk and the cumulative proportion of metastases and death by centiles of PSA distribution, and used these estimates to examine a series of practical questions about screening age and intervals.

One of the limitations of this study is that the data come from white Swedish men in 1 town, so the conclusions might not carry over to other populations.

Hypothesis-Generating, Not Ready for Clinical Use

Approached for comment, William Catalona, MD, professor of urology and director of the Clinical Prostate Cancer Program at Northwestern University Feinberg School of Medicine in Chicago, Illinois, told Medscape Medical News that there are 2 components to this study that should be considered — at what age to begin PSA testing, and at what age to stop PSA testing.

For the first question of when to start PSA testing, this study replicates in a large patient population several previous studies that show there is merit to begin PSA testing in men in their 40s, as recommended by the current guidelines from the National Comprehensive Cancer Network (NCCN). For the second question of when to stop PSA testing, it refers to a previous study by Dr. Vickers in a small population from Sweden that has never been replicated. "It would be unwise to base any recommendation on such a small, single, unvalidated study, in my opinion," Dr. Catalona commented.

These are "provocative data, which I place as more hypothesis generating and not practice changing," commented Marc Garnick, MD, a clinical professor of medicine at Harvard Medical School with an oncology practice at Beth Israel Deaconess Medical Center in Boston, Massachusetts. Dr. Garnick is also editor in chief of Harvard Medical School Annual Report on Prostate Diseases.

Approached for comments on the paper, Dr. Garnick told Medscape Medical News, "The interesting aspect of the findings is the identification of a group of patients who could serve as a basis for a randomized study. For example, the high-risk cohorts that had the highest decile PSA should be entered into a clinical study where they could be biopsied and if cancer was found, treated and compared to standard practice or compared to a group who are also diagnosed but left untreated. What we are searching for is a test that identifies a higher likelihood of finding more biologically aggressive cancer and evaluating whether any intervention alters its natural history. Thus far the level I evidence from the screening studies has failed to show this.

"While this paper may identify methods for 'smarter screening,' I take issue with the final statement of the manuscript that 'a risk stratified approach to PSA screening will improve the ratio of its benefits and harms'," Dr. Garnick commented. "We have to prove this statement and the Vickers finding now potentially allows us to use this risk-stratified approach to identify patients for clinical trials."

However, Dr. Garnick also added that "relying solely on any iteration of PSA testing is becoming passé, as other more precise biomarkers of risk are quickly becoming mainstream."

The study was funded by the National Cancer Institute, the Swedish Cancer Society, and several academic cancer centers. Dr. Vickers and 2 of his coauthors are named as coinventors on a patent application for a statistical method to predict the results of prostate biopsy. Dr. Vickers reports receiving support from GlaxoSmithKline and Genomic Health for the study. Senior author Hans Lilja reports holding patients for free PSA, intact PSA, and hK2 assays. Other conflicts of interests are detailed in the paper.

BMJ. Published online April 16, 2013. Abstract


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