Efficacy of prostate cancer screening still uncertain

The use of prostate cancer screening with PSA testing and digital rectal exams still remains unclear after the results of two major trials testing the methods were published online yesterday in The New England Journal of Medicine.

In fact, results from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial showed an increased mortality in those men who underwent screening for the disease.

Researchers in the trial randomly assigned 76,693 men at 10 U.S. centers to receive either annual screening with PSA or digital rectal exams (n=38,343) or usual care (n=38,350). After seven years of follow-up, 2,820 cancers had been diagnosed in the screening group compared with 2,322 in the control group (rate ratio=1.22; 95% CI, 1.16-1.29). At 10 years, 3,452 men in the screening group were diagnosed with cancer compared with 2,974 in the control group (rate ratio=1.17; 95% CI, 1.11-1.22).

However, the increased number of cancer diagnoses did not result in a lower rate of mortality. At seven years follow-up, there were 50 prostate cancer deaths in the screening group compared with 44 in the control group (rate ratio=1.13; 95% CI, 0.75-1.70). At 10 years, there were 92 prostate cancer deaths in the screening group and 82 in the control group (rate ratio=1.11; 95% CI, 0.83-1.50).

“What this report tells us is that there may be some men who are diagnosed with prostate cancer and have the side effects of treatment, such as impotence and incontinence, with little chance of benefit,” John E. Niederhuber, MD, director of the NCI, said in a press release.

“Screening was associated with no reduction in prostate-cancer mortality during the first seven years of the trial, with similar results through 10 years, at which time 67% of the data were complete,” the researchers wrote.

Follow-up for this trial is planned to continue for a total of 13 years.

ERSPC data

The second trial examined the effect of screening with PSA testing alone. Researchers conducting the European Randomized Study of Screening for Prostate Cancer randomly assigned 182,000 men aged 50 to 74 years to either screening with PSA once every four years or a control group that did not receive screening.

At nine years follow-up, 8.2% of the screening group was diagnosed with prostate cancer; 4.8% of the control group was diagnosed. As of Dec. 31, 2006, the researchers confirmed 214 prostate cancer-related deaths in the group screened with PSA compared with 326 deaths in the control group. PSA-based screening for prostate cancer had a 20% reduced rate of death (95% CI, 0.65-0.98). When researchers looked at only those men who were actually screened during the first round, the rate ratio for death from prostate cancer was 0.73, or a 27% reduced rate of death (95% CI, 0.56-0.90).

“The report on the ERSPC trial appropriately notes that 1,410 men would need to be offered screening and an additional 48 would need to be treated to prevent one prostate cancer death during a 10-year period, assuming the point estimate is correct. And although the PLCO trial may not have the power as yet to detect a similarly modest benefit of screening, its power is already more than adequate to detect important harm through overdiagnosis,” Michael J. Barry, MD, professor in the department of medicine, Harvard Medical School, wrote in an accompanying editorial.

“However, the implications of the trade-offs reflected in these data, like beauty, will be in the eye of the beholder. Some well-informed clinicians and patients will still see these trade-offs as favorable; others will see them as unfavorable. As a result, a shared decision-making approach to PSA screening, as recommended by most guidelines, seems more appropriate than ever,” he wrote.

Andriole GL. N Engl J Med. 2009;360:1310-1319.
Barry MJ. N Engl J Med. 2009;360:1351-1354.
Schröder FH. N Engl J Med. 2009;360:1320-1328.

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