Study Knocks Diagnostic Value of Prostate Cancer Screening Test

Feb. 25, 2010— -- If prostate biopsies were based only on the rate of change in PSA level over time, the number of unnecessary biopsies would be almost four times the number of additional cancers diagnosed, data from a large clinical trial showed.

In the absence of other predictive factors, so-called PSA 'velocity' would have identified 115 prostate cancers at a cost of 433 unnecessary biopsies, according to Andrew Vickers of Memorial Sloan-Kettering Cancer Center in New York City and colleagues.

If used as sole justification for a biopsy, PSA velocity would trigger about one of every seven prostate biopsies, they reported online in the Journal of the National Cancer Institute.

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Moreover, adding PSA velocity to a multifactor model resulted in minuscule improvement in diagnostic accuracy, particularly for high-grade cancers.

The findings have implications for clinical guidelines that include PSA velocity in criteria for prostate biopsy, including recommendations from the American Urological Association (AUA) and the National Comprehensive Cancer Network (NCCN).

"We found no reason to believe that implementation of the guideline would improve patient outcomes; indeed, its use would lead to a large number of unnecessary biopsies," Vickers and co-authors wrote in conclusion. "We therefore recommend that organizations issuing policy statements related to PSA and prostate cancer detection remove references to PSA velocity."

The authors did acknowledge that current clinical guidelines for prostate cancer have a strong evidentiary base for many aspects of diagnosis, evaluation, and treatment; in particular, use of PSA and free PSA levels to diagnose cancer.

However, they noted, inclusion of PSA velocity in clinical recommendations has questionable support.

Predictive Value?

The NCCN guidelines, for example, recommend prostate biopsy in men who have a PSA velocity greater than 0.35 ng/mL-1 y-1. In support of the recommendation, the guideline authors cited a single study showing that PSA velocity predicted diagnosis of fatal prostate cancer 10 to 15 years later.

"It is unclear why a marker that predicts aggressive prostate cancer many years in the future should be used to suggest immediate biopsy to patients," Vickers and colleagues wrote. "Moreover, PSA velocity was not demonstrated to add predictive accuracy to PSA alone."

To examine the predictive value of PSA velocity, the authors analyzed data from the Prostate Cancer Prevention Trial, which included an end-of-trial prostate biopsy for all study participants (N Engl J Med 2003; 349: 215-224). The analysis included 5,519 men from the placebo arm of the trial.

Vickers and colleagues constructed a linear regression model that incorporated various predictors of prostate cancer on biopsy. They compared results in models with and without PSA velocity. They also performed an analysis that limited the definition of prostate cancer to high-grade disease (Gleason score 7 to 10).

In a univariate analysis, PSA velocity had a significant association with biopsy outcome (P<0.001). As a component of a multivariable prediction model, however, the association was substantially diminished.

Varying the definition of PSA velocity, the authors found marginally significant associations with log(PSA) values one year before diagnosis (OR 0.74, P=0.037) and annualized velocity (OR 0.98, P=0.047).

Receiver operating characteristic analysis showed minimal improvement in the area under the curve (AUC) when PSA velocity was added to other predictors of prostate cancer risk (AUC 0.702 versus AUC 0.709).

Even less improvement in predictive accuracy was observed for detection of high-grade or clinically significant cancers.

"There was little evidence that PSA velocity adds an important level of predictive accuracy to either standard predictors or to PSA alone," the authors wrote.

"Superior risk stratification can be achieved simply by choosing a different PSA cut point, especially for the endpoints of high-grade cancer or clinically significant cancer," they added.

The Prostate Cancer Prevention Trial used a PSA cutoff of 4.0 ng/mL as a biopsy trigger, resulting in a biopsy rate of approximately one in 20 with no appreciable loss in diagnostic accuracy, Siu-Long Yao, PhD, and Grace L. Lu-Yao, PhD, of the University of Medicine and Dentistry of New Jersey, wrote in an accompanying editorial.

Imperfect Screening Test

The study by Vickers et al. serves as a reminder that "the use of PSA as a screening tool leaves much to be desired," wrote Yao and Lu-Yao. "Indeed, after more than 20 years of PSA screening, it has been estimated that approximately one million men may have been unnecessarily treated for clinically insignificant prostate cancer."

"The shortcomings of PSA testing also remind us that there is still much art to the diagnosis and treatment of prostate cancer."