PSA SCREENING DEBATE CONTINUES

June 28, 2012 — The US Preventative Services Task Force's (USPSTF's) recent report recommending against routine prostate cancer screening "contained a number of important errors of fact, interpretation, and statistics," according to the authors of an essaypublished online June 18 in the Journal of Clinical Oncology.

Perhaps most important, the USPSTF's characterization of the evidence against screening as being of "moderate or high certainty," and thus deserving of its D rating, is a "critical error," suggest the authors, led by Sigrid Carlsson, MD, PhD, from the Memorial-Sloan Kettering Cancer Center in New York City and Göteborg University in Sweden.

The USPSTF did not competently assess the mortality benefit of screening, the authors say, and this error alone casts doubt on their grading of prostate-specific antigen (PSA) testing.

Dr. Carlsson and coauthors, who include academics from the Netherlands and Finland, also say the USPSTF's "blanket rejection" of the PSA test is "unlikely to influence practice."

Despite excoriating the new guidelines, the essay authors are sympathetic with the USPSTF's ruling.

"PSA testing is not likely to go away, and...this is perhaps a good thing," they opine, suggesting that the mortality benefit of screening has the potential to redeem the harms caused by the test

It was "reasonable" of the USPSTF to recommend against PSA screening "as currently implemented" in the United States, they say.

In other words, the authors see problems all around: with both the USPSTF and their bungling of evidence and with US urologists and their misuse of the PSA test and overtreatment of the disease. The clinical practices that are in need of reform, the authors say, include the well-documented problems of administering the test to men too old/sick to benefit, overuse of biopsy, and overtreatment (accompanied by underuse of active surveillance).

The authors, who assert that PSA screening provides a valuable disease-specific mortality benefit, have a prescription for repairing the testing in the United States: "Our goal should...be to maximize the benefits of PSA testing and minimize its harms."

"Best" Studies Reveal Mortality Benefit

The largest active prospective trial of PSA screening is the European Randomized Study of Screening for Prostate Cancer (ERSPC), which is still ongoing. In other words, the trial has only provided interim results (9 years) and has not yet reported at its prespecified main follow-up time. This is highly important because it proves that the USPSTF made "definitive conclusions" based on this "incomplete data," say the essay authors.

In addition, a very recent analysis from the ERSPC that used 2 additional years of follow-up (11 years median) continues to show that the screening, as practiced in Europe, significantly reduces prostate cancer mortality by about 20% (relative risk, 0.79; 95% confidence interval, 0.68 - 0.91; P = .001).

Furthermore, the authors believe that only the ERSPC and the Göteborg screening trial are of good quality. Other trials had methodological problems, including the US Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) trial, which had a high rate of "contamination," with more than half of the men in the control (no testing) group receiving PSA testing outside the study by year 6 of the trial.

The USPSTF combined lesser-quality trials with top-flight data and made a mess of the combined analysis, assert the essay authors.

The "best trials" that are available have demonstrated that screening can reduce prostate cancer death by 20% to 44%, referring to data from the ERSPC and Göteborg trials, respectively, say Dr. Carlsson and colleagues.

This evidence alone, suggest the authors, challenges the USPSTF's final grade D assessment of PSA testing that "there is moderate or high certainty that this service has no net benefit or that the harms outweigh the benefits."

Other critical errors in the USPSTF report include the fact that the USPSTF assessed whether or not PSA testing decreases overall mortality (and not just disease-specific mortality). Only disease-specific mortality is statistically robust in these cancer screening trials, say the essay authors.

The USPSTF authors state that, in screening trials, "48 men received treatment for every prostate cancer‐specific death prevented." "This is false," write the essay authors, who say this number (48) was calculated from the number of men diagnosed, not the number treated.

The USPSTF also made a glaring error in another section of the report, according to the essayists

In addition, there is a further problem with this statistic: it depends on length of follow-up. For instance, in the long-running Göteborg trial, the number needed to diagnose to prevent a death is only 12 (at 14 years of follow-up). This number is much higher, at 37, for the ERSPC, which has less follow-up, they explain.

Rx for Improvement in PSA Screening Outcomes in the United States

Three broad reforms are needed in the United States among clinicians, say the essay authors.

"First, avoid PSA tests in men with little to gain. There is no justification for recommending PSA screening in asymptomatic men with a short life expectancy," they write.

Second, do not treat men with low-risk prostate cancers immediately. "A high proportion of men with screen-detected prostate cancer do not need immediate treatment and can be managed by active surveillance," the authors say.

"Third, refer men who do need treatment to high-volume centers." Having more patients treated by high-volume providers "will improve cancer control and decrease complications," the authors conclude.

Dr. Carlsson has no conflicts of interest. Some coauthors have ties to industry, and 2 have patents pending for tests related to prostate cancer screening.

J Clin Oncol. Published online June 18, 2012. Full text