We used a nested case-control design on data from men in four prospective 
studies (from the UK, Maryland in the USA, and two from Finland) with available 
stored serum samples to determine whether there was an advantage in measuring 
both free prostate-specific antigen (PSA) and total PSA as a potential screening 
test for prostate cancer. Of these men, 247 were verified through national vital 
statistics offices as having died of prostate cancer, or having developed the 
disease, and 953 men who did not develop prostate cancer (controls) were 
selected, matched to cases for age, study centre and sample storage duration. 
Fixing the false-positive rate at 1%, the prostate cancer detection rate 
(sensitivity) over the 3 years following serum collection (based on 14 cancers) 
increased from an estimated 95% using total PSA to 97% using free and bound PSA 
(that is, bound to alpha-antichymotrypsin which together with the free form is 
total PSA). Over a 6-year period (based on 41 cancers) a similar difference 
occurred (52% and 56% detection rates respectively). We conclude that there is 
no material advantage in adding free to total PSA in prostate cancer screening 
trials.