PROSPECTIVE OBSERVATIONAL STUDY TO ASSESS VALUE OF PROSTATE-SPECIFIC ANTIGEN AS SCREENING-TEST FOR PROSTATE-CANCER

Objective-To evaluate measurement of serum prostate specific antigen a s a potential screening test for future clinical prostate cancer among healthy men. Design-Nested case-control study with stored serum sampl es collected from 49261 men with follow up using national death and ca ncer registration systems. Subjects-265 asymptomatic men who subsequen tly developed clinical prostate cancer and 1055 controls matched for a ge, study centre, and duration of storage of samples. Main outcome mea sures-Distribution of concentrations of the antigen in men who develop ed prostate cancer and in controls. Results-Prostate specific antigen concentrations were significantly higher in men who subsequently devel oped prostate cancer than in controls. In the first three years after blood collection the median concentration was 23 times greater in case s than in controls of the same age at the same centre (that is, 23 mul tiples of the median). A smaller difference persisted thereafter; 4.0 multiples of the median 3-6 years after blood collection, 3.6 6-10 yea rs, and 1.8 after 10 years. In the first three years the proportion of men who developed prostate cancer and had raised levels of the antige n (greater than or equal to 12 multiples of the median) (detection rat e or sensitivity) was 81% (95% confidence interval 54% to 96%). The pr oportion of men who did not develop prostate cancer but had levels thi s high (false positive rate) was only 0.5%. Conclusion-Prostate specif ic antigen measurement is a highly discriminatory screening test for p rostate cancer among healthy men. In the general population, 60-74 yea r old men who had greater than or equal to 12 times the normal median level would have about a 50% chance of developing clinical prostate ca ncer in the next three years. Measurement of this antigen is a good en ough screening test to justify a randomised controlled trial to determ ine any reduction in mortality from prostate cancer.