'Important Errors' in USPSTF Report on PSA Testing

Reform Needed Among Urologists

Nick Mulcahy

June 28, 2012

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

Perhaps most important, the characterization of the evidence against screening as being of "moderate or high certainty," and thus deserving of its D rating, is a "critical error," note the essayists, 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; this error alone casts doubt on the grading of prostate-specific antigen (PSA) testing, the essayists state.

Dr. Carlsson and colleagues (some of whom are academics from the Netherlands and Finland) also note that the USPSTF's "blanket rejection" of the PSA test is "unlikely to influence practice."

PSA testing is not likely to go away.

"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.

Despite excoriating the new guidelines, the essayists are sympathetic with the USPSTF ruling. It was "reasonable" of the USPSTF to recommend against PSA screening "as currently implemented" in the United States, they say.

In other words, they see problems all around — with the USPSTF's bungling of evidence and with the misuse of the PSA test and overtreatment of the disease by American urologists. The clinical practices that are in need of reform, the essayists write, include the well-documented problems of administering the test to men too old or too sick to benefit, overuse of biopsy, and overtreatment (accompanied by underuse of active surveillance).

Dr. Carlsson and colleagues, 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 ongoing. 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 "incomplete data," the essayists note.

In addition, a very recent analysis from the ERSPC that used 2 additional years of follow-up (median, 11 years) 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 essayists believe that only the ERSPC and the Göteborg screening trial are of good quality. Other trials had methodologic problems, such as the US Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) trial, which had a high rate of "contamination"; more than half of the men in the control (no testing) group had undergone 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, the essayists assert.

The "best trials" available — the ERSPC and Göteborg trials — have demonstrated that screening can reduce prostate cancer death by 20% to 44%, Dr. Carlsson and colleagues note.

This evidence alone, they suggest, challenges the final grade D assessment for PSA testing, which indicates 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 (not just disease-specific mortality). Only disease-specific mortality is statistically robust in these cancer screening trials, write the essayists.

They note that the USPSTF also made a glaring error in another section of the report.

This is false.

In screening trials, "48 men received treatment for every prostate cancer-specific death prevented," according to the USPSTF report. "This is false," write the essayists, who say the number 48 was calculated from the number of men diagnosed, not the number treated.

There is another problem with this statistic: it depends on length of follow-up. For instance, in the long-running (14-year) Göteborg trial, the number needed to diagnose to prevent 1 death is only 12. However, in the ERSPC trial, which had a shorter follow-up, the number is 37, they explain.

Improving PSA Screening Outcomes in the United States

Clinicians in the United States can make 3 broad reforms to improve screening outcomes, the essayists assert.

"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 explain.

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," they note.

"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," Dr. Carlsson and colleagues conclude.

Dr. Carlsson has disclosed no relevant financial relationships. Some of her 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


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