'Verification Bias' Removed, PSA of 2.6 Now Upper Limit of Normal
Stimulus for the Times editorial was an article in the July 24 issue of the New England Journal of Medicine, "Effect of Verification Bias on Screening for Prostate Cancer by Measurement of Prostate-Specific Antigen." In their premise for this article, the Harvard authors state that previous studies have failed to take into account the fact that only a fraction of men screened have actually had their disease status adequately verified. Thus, the true value of PSA as a screening test may be different from the numbers usually quoted.
The authors applied a mathematical model that estimates probability of prostate cancer in a population as a function of the following clinical variables: digital rectal exam, race, family history, PSA level, and age. A fitted logistic regression model was taken from the subgroup undergoing biopsy to predict the probability of prostate cancer in the entire group. Adjusted ROC curves were then derived by calculating the probability of being in a particular PSA category for men in the entire sample with and without prostate cancer. The study showed that after correction for verification bias, improvement in both sensitivity and specificity of PSA screening is observed. The key figure is shown here.
From analysis of the ROC curves, the authors found "that lowering
the threshold for biopsy from 4.1 to 2.6 ng per milliliter in men younger
than 60 years would double the cancer-detection rate from 18 percent to
36 percent, whereas the specificity would fall
only from 0.98 to 0.94." The authors concluded, "Both of these findings support the use of a lower threshold PSA value for a recommendation of biopsy."
In a NEJM editorial accompanying the article,
Fritz Shroder from Rotterdam cautioned that "lowering the PSA threshold
for performing a biopsy will increase the rate of overdiagnosis and, potentially,
overtreatment. New recommendations for screening should arise from ongoing,
randomized studies that are designed to show whether screening indeed
reduces mortality from prostate cancer without unacceptably reducing the
quality of life."
The New York Times editorial concluded that, "The deeper problem is that no one has yet demonstrated that finding prostate tumors early saves lives or improves health."