Evidence lacking for routine prostate screening, but single test at 60 may help

An analysis of randomized, controlled trials did not find support for routine population screening for prostate cancer, although a single prostate-specific antigen (PSA) test at age 60 could identify those most likely to develop and die from the disease.

Researchers at the University of Florida reviewed six trials involving 387,286 participants. They found in BMJ that screening helps diagnose prostate cancer at an earlier stage, but does not significantly reduce mortality while risking overtreatment.

Six randomized, controlled trials from January 2005 to July 2010 totaled 387,286 participants. Screening was associated with increased diagnosis of prostate cancer (relative risk [RR], 1.46; 95% CI, 1.21 to 1.77; P<0.001) and stage I prostate cancer (RR, 1.95; 95% CI, 1.22 to 3.13; P=0.005). But there was no significant effect of screening on death from prostate cancer (RR, 0.88; 95% CI, 0.71 to 1.09; P=0.25) or overall mortality (RR, 0.99; 95% CI, 0.97 to 1.01; P=0.44).

All the trials had substantial methodological limitations and none provided data on the effects of screening on quality of life. The authors suggest men should be better informed about the uncertainties associated with screening, “that is, detection of cancer that will not negatively affect survival.”

Instead, clinicians should focus attention on screening men at age 60 and finding out who has PSA levels above 2 ng/mL, according to a second study. Researchers in Sweden and at Memorial Sloan Kettering Cancer Center in New York determined that a single PSA test at age 60 strongly predicts a man's lifetime risk of diagnosis and mortality.

They found in BMJ that 90% of prostate cancer deaths occurred in men who'd had the highest PSA levels at age 60. Men with average or low PSA levels had negligible rates of prostate cancer or death by age 85. Results suggest that at least half of men aged 60 and older might not need prostate cancer screening, which could reduce overdiagnosis and overtreatment.

The researchers conducted a case-control study of 1,167 Swedish men born in 1921 who'd provided blood samples in 1981 and were followed to age 85. The blood samples were of archival anticoagulated plasma. Few men in that time period had undergone PSA screening, avoiding verification bias.

There were 43 cases of metastasis and 35 deaths from prostate cancer. PSA levels at age 60 were associated with prostate cancer metastasis (area under the curve [AUC], 0.86; 95% CI, 0.79 to 0.92; P<0.001) and death from prostate cancer (AUC, 0.90; 95% CI, 0.84 to 0.96; P<0.001).

Although only a minority of the men with PSA concentrations in the top quarter (>2 ng/mL) developed fatal prostate cancer, 90% (78% to 100%) of deaths from prostate cancer occurred in these men. Conversely, men aged 60 with PSA concentrations at the median or lower (<1 ng/mL) were unlikely to have clinically relevant prostate cancer (0.5% risk of metastasis by age 85 and 0.2% risk of death from prostate cancer). Though the latter group might harbor prostate cancer, it is unlikely to become life-threatening, the researchers concluded. Overall, men with PSA levels of 2 ng/mL or greater at age 60 had 26 times (95% CI, 2 to 113 times) the odds of dying from prostate cancer.

An accompanying editorial suggested that younger men at high risk of prostate cancer, such as those with a strong family history and higher baseline PSA concentrations, should be followed closely, while elderly men and those with a low risk of disease could be tested less often, if at all. “Approaches such as these will hopefully make the next 20 years of PSA-based screening better than the first 20,” the editorialist wrote.