European study finds prostate cancer mortality reduced by PSA screening

Prostate-specific antigen (PSA)-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality, according to two more years of follow-up results in the European Randomized Study of Screening for Prostate Cancer (ERSPC).

ERSPC involved 182,160 men between the ages of 50 and 74 in eight European countries. Men randomly assigned to the screening group were offered PSA-based screening, whereas those in the control group were not. Screening was carried out every four years (every two years in Sweden). The primary outcome was mortality from prostate cancer. A positive test result, defined as a PSA value of 3.0 ng/mL or more, was an indication for sextant prostatic biopsies. Study results appeared in the March 15 New England Journal of Medicine.

There were 299 deaths from prostate cancer in the screening group and 462 in the control group, with death rates of 0.39 and 0.50 per 1,000 person-years, respectively. Overall, a rate ratio of 0.79 (95% CI, 0.68 to 0.91; P=0.001), was found for prostate cancer mortality between the screened group and unscreened. The absolute difference in mortality amounted to 0.10 death per 1,000 person-years, or 1.07 deaths per 1,000 men randomized.

After correction for selection bias and noncompliance, an adjusted rate ratio of 0.71 (95% CI, 0.58 to 0.86) was found. Rate ratios for the period of 1 to 9 years and the period of 1 to 11 years were 0.85 (95% CI, 0.71 to 1.03) and 0.79 (95% CI, 0.67 to 0.92), respectively.

To prevent one death from prostate cancer in 11 years of follow-up, 1,055 men would need to be invited for screening (NNI) and 37 cancers would need to be detected (NND). The NNI and NND varied considerably according to the length of follow-up at all centers (NNI range, 936 to 2,111; NND range, 33 to 80) and at the three largest centers (NNI range, 194 to 1,825; NND range, 8 to 42). There was no significant difference in all-cause mortality between the screened and unscreened groups.

The authors wrote that reduction in prostate-cancer mortality needs to be balanced against the disadvantages of early detection of prostate cancer, with overdiagnosis estimated to occur in approximately half of screening-detected cancers. “More information on the balance of benefits and adverse effects, as well as the cost-effectiveness, of prostate-cancer screening is needed before general recommendations can be made,” they wrote.

The results contradict those of the U.S.-based Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, probably reflecting differences in the studies' respective populations and protocols, an editorialist said. For example, screening-detected cancers were treated differently. In the European screening group, men diagnosed with prostate cancer were more likely to have been treated at an academic center than were men in the control group.

“We are left with an unsatisfactory situation, in which many practitioners will think there are insufficient data to recommend abandoning PSA screening for prostate cancer,” the editorialist wrote. “However, the findings of the PLCO trial are more applicable to the situation in the United States, since the ERSPC was conducted in a largely PSA-naive population. Therefore, an intensification of PSA screening would be unwise, and I think it would be advisable to follow the preliminary recommendations of the U.S. Preventive Services Task Force.”