Ulmert D et al. (2008) Prostate-specific antigen at or before age 50 as a predictor of advanced prostate cancer diagnosed up to 25 years later: a case–control study. BMC Med 6: 6

Lilja and colleagues previously reported that serum PSA level in men aged ≤50 years was a strong predictor of prostate cancer diagnosed up to 25 years afterwards. However, the researchers concede that many prostate cancers do not cause morbidity or mortality and have, therefore, reanalyzed their data using locally advanced or metastatic disease at diagnosis as the clinical end point.

Participants for the case–control study were selected from a population-based cohort of 21,277 men from Sweden who provided blood samples between 1974 and 1986 when aged ≤50 years. Cases of locally advanced or metastatic prostate cancer through 1999 were identified (n = 161; median 17 years from blood-sample collection to diagnosis) and controls were matched for blood-sample collection date and age (cases were matched with 3 (73%), 2 (24%) or 1 (3%) controls). Researchers measured serum levels of total PSA, free PSA and human kallikrein 2 in the original blood samples.

Total PSA was strongly predictive of a subsequent diagnosis of advanced prostate cancer (area under the curve 0.791); the other two markers were much less strongly predictive. Even moderately raised serum PSA levels considerably increased the risk of advanced disease, and the 20% of the population with the highest PSA levels (≥0.9 ng/ml) accounted for 66% of the advanced cancer cases.

The researchers recommend that a PSA test before 50 years of age could select at-risk patients for intensive screening, which would optimize the benefit of screening whilst minimizing the potential for harmful overtreatment.