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Authors Vickers AJ, Cronin AM, Björk T, et al
Review Date Oct 2010
Citation Br Med J 2010;341:c4521
One of the problems with prostate-specific antigen (PSA) testing for prostate cancer is that of over-treatment, that is, diagnosing and treating cancers (with potentially serious side-effects) that are not likely to ever cause symptoms or shorten life. This is of particular relevance to older men with life expectancies of 10-20 years who may not benefit from having prostate cancers detected at this stage of their lives.
To determine the relationship between concentrations of PSA at age 60 and subsequent diagnosis of clinically relevant prostate cancer in an unscreened population, to evaluate whether screening for prostate cancer and chemoprevention could be stratified by risk.
Design: Case-control study with 1:3 matching nested within a highly representative population based cohort study.
Setting: General population of Sweden taking part in the Malmo Preventive Project. Cancer registry at the National Board of Health and Welfare.
Participants: 1167 men aged 60 who provided blood samples in 1981 and were followed up to age 85.
Main Outcome Measure: Metastasis or death from prostate cancer.
The rate of screening during the course of the study was low and no cancers were detected by screening. There were 43 cases of metastasis and 35 deaths from prostate cancer. Concentration of prostate specific antigen at age 60 was associated with prostate cancer metastasis (area under the curve 0.86, 95% confidence interval 0.79 to 0.92; P<0.001) and death from prostate cancer (0.90, 0.84 to 0.96; P<0.001). The greater the number for the area under the curve (values from 0 to 1) the better the test.
Although only a minority of the men with concentrations in the top quartile (>2 ng/ml) develop fatal prostate cancer, 90% (78% to 100%) of deaths from prostate cancer occurred in these men. Conversely, men aged 60 with 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).
The concentration of prostate specific antigen at age 60 predicts lifetime risk of metastasis and death from prostate cancer. Though men aged 60 with concentrations below the median (</=1 ng/ml) might harbour prostate cancer, it is unlikely to become life threatening. Such men could be exempted from further screening, which should instead focus on men with higher concentrations.
Points to Note
- Several studies are now suggesting that PSA levels measured at relatively young ages can be used to guide PSA testing frequency, so that resources can be focused on men most likely to develop metastases or die from prostate cancer and to reduce the risk of over-diagnosis.
- PSA concentration at age 60 can predict clinically significant prostate cancer up to 25 years later in this population.
- Although 90% of prostate cancer deaths occurred in men with PSA> 2ng/ml (highest quartile) at age 60, the risk for men in this group was quite low i.e. most men in this group did not develop fatal prostate cancer. These concepts can be confusing for men and may need to be clarified during counselling.
- The findings suggest that men at age 60 with PSA concentration <1 ng/ml can be reassured that they are highly unlikely to develop a prostate cancer that will shorten their life and could be screened much less frequently than those with higher PSA levels.
- These findings need to be replicated in other populations, particularly in men from other racial groups known to have different overall risks of prostate cancer incidence and mortality.