Nick Mulcahy

March 19, 2014

HOLLYWOOD, Florida — Updated guidance from the National Comprehensive Cancer Network (NCCN) seeks to establish a "middle ground" for the use of prostate-specific antigen (PSA) testing in men in the United States, said an official here at the NCCN 19th Annual Conference.

The guidance falls between the extremes of "testing nobody" and "testing everybody," Peter Carroll, MD, told Medscape Medical News. The latter, he said, involves "aggressive and repeated screening."

Dr. Carroll is chair of the NCCN Prostate Cancer Early Detection Panel and professor of urology at the University of California, San Francisco.

The updated guidance "strikes a nice balance," he said in an email.

Overall, the guidance, which was previously "very, very complicated," is now "very much simplified," added panel member Andrew Vickers, PhD, a biostatistician at the Memorial-Sloan Kettering Cancer Center in New York City.

Notably, the guideline recommends routine PSA testing for all healthy men starting at age 45 and continuing, in some cases, past age 70.

That advice represents more of a fringe than a middle ground, suggested a critic.

The NCCN guidelines still take a more aggressive stance.

"The [updated] NCCN guidelines still take a more aggressive stance toward PSA testing than do the recent guidelines issued by the American College of Physicians, the American Cancer Society, and American Urology Association [AUA]," said Richard Hoffman, MD, professor of internal medicine at the University of New Mexico in Albuquerque.

For example, the most recent guidance from the AUA calls for routine PSA testing in healthy men, but only for those 55 to 69 years of age.

The NCCN guidance obviously conflicts with the US Preventive Services Task Force recommendation against PSA testing in healthy men, Dr. Hoffman noted. That organization said the potential harms outweigh the benefits.

Still, the updated NCCN guidelines are an improvement from the old NCCN recommendations. "The new version is designed to be more evidence-based and to reduce testing and overdiagnosis," he said in an email.

Both Dr. Carroll and Dr. Vickers emphasized that the key to the usefulness of the updated guidance is that it is linked to the NCCN prostate cancer treatment guidelines.

This should translate into less overtreatment, they said.

The NCCN has famously recommended the use of active surveillance instead of definitive treatment in early-stage low-risk disease. This surveillance strategy is an effort to reduce overtreatment, and thus harm, in men with prostate cancers that are ultimately indolent. Half of all PSA-detected prostate cancers are low-risk disease, Dr. Vickers explained.

Overall, the updated guidance seeks to "maximize the benefit and minimize the harm" of PSA testing, he said.

Nevertheless, Dr. Hoffman, as an internist, has a pointed complaint about the NCCN recommendation to use PSA testing in age groups that have not been evaluated in randomized controlled trials.

"I do not appreciate being expected to take time away from offering proven preventive services [for prostate cancer] to discuss testing strategies — starting at age 45, continuing past 70 — for which there is no convincing evidence," he said.

Start of Testing at Age 45

The "best evidence supports the use of serum PSA for the early detection of prostate cancer," according to the discussion section of the updated NCCN guidelines on the early detection of prostate cancer.

However, the specifics of when, who, and how often to perform PSA testing "remain major topics of debate," the report reads.

So how did the NCCN decide on age 45, which is an apparently novel age at which to start testing?

The decision was not made of the basis of evidence from the recent randomized trials conducted in Europe, which found a mortality benefit with screening but focused primarily on men 55 to 69 years of age.

Instead, the recommendation comes from observational data that suggest baseline PSA testing of men in their 40s and early 50s might allow for future prostate cancer risk stratification.

Some of these data come from a large study of Swedish men in which a single PSA test before age 50 predicted subsequent prostate cancer risk up to 30 years later, as reported by Medscape Medical News.

"This suggests that one could perform early baseline testing and then determine the frequency of testing based on risk," reads the updated NCCN guidance.

In the words of Dr. Carroll, "a baseline PSA trumps family history or ethnicity as a [prostate cancer] risk factor."

Indeed, the updated guideline calls for informed testing starting at age 45, with annual to biannual testing in those with a PSA above the age-specific median. For those below the median, a retest at age 50 is recommended.

The median PSA levels are 0.7 ng/mL for men 40 to 49 years of age and 0.9 ng/mL for men 50 to 59 years.

Annual or biannual follow-up is recommended for all men with a PSA value above 1.0 ng/mL.

The suggestion to start men 45 to 49 years is troubling.

Dr. Hoffman does not agree with this strategy. "The suggestion to start discussions about a baseline PSA test in men 45 to 49 years is troubling," he said.

"We have no evidence that closely following men with an elevated PSA level will ultimately reduce prostate cancer mortality," he explained. Testing younger men could lead to more false-positive results and unnecessary biopsies, Dr. Hoffman pointed out.

Also, he noted, it is not known whether treating a cancer diagnosed at age 50 results in worse outcomes than treating a cancer diagnosed at age 45.

"However, we do know that the younger men will have that much longer to live with treatment complications and the psychological burdens of a cancer diagnosis," he argued.

Screening Past Age 70 and When to Biopsy

Identifying the ideal age at which to discontinue testing is "even more elusive" than determining the start age, according to the NCCN panel.

The panel members uniformly agreed that PSA testing should only be offered to men with a life expectancy of more than 10 years. However, the stop date was not a unanimous decision.

Therefore, the NCCN offers clinicians a set of cut-offs. Clinicians can discontinue screening at age 69; continue screening up to age 74 but increase the PSA threshold for biopsy in men 70 to 74 years; or discontinue screening at 75 years for men who have a PSA below 3.0 ng/mL.

Again, Dr. Hoffman has concerns about this guidance.

"The updated version is also in contrast with other guidelines, including the AUA, which have backed off from recommending screening for men over the age of 70," he said.

The updated NCCN guideline also states that men should generally be referred for a prostate tissue biopsy when their PSA exceeds 3 ng/mL.

This creates "problems," said Dr. Hoffman. "PSA increases with age, and using this low threshold will increase the number of false-positive tests and subject men to the harms of biopsy, which are now recognized to include a substantial risk for serious infections," he explained.

The AUA suggests a biopsy threshold of 10 ng/mL to reduce these risks, he added.

National Comprehensive Cancer Network (NCCN) 19th Annual Conference. Presented March 14, 2014.


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