From an article in the New England Journal of Medicine 27 May 2004.

Background The optimal upper limit of the normal range for
prostate-specific antigen (PSA) is unknown. We investigated the
prevalence of prostate cancer among men in the Prostate Cancer
Prevention Trial who had a PSA level of 4.0 ng per milliliter or less.

Methods Of 18,882 men enrolled in the prevention trial, 9459 were
randomly assigned to receive placebo and had an annual measurement of
PSA and a digital rectal examination. Among these 9459 men, 2950 men
never had a PSA level of more than 4.0 ng per milliliter or an
abnormal digital rectal examination, had a final PSA determination,
and underwent a prostate biopsy after being in the study for seven
years.

Results Among the 2950 men (age range, 62 to 91 years), prostate
cancer was diagnosed in 449 (15.2 percent); 67 of these 449 cancers
(14.9 percent) had a Gleason score of 7 or higher. The prevalence of
prostate cancer was 6.6 percent among men with a PSA level of up to
0.5 ng per milliliter, 10.1 percent among those with values of 0.6 to
1.0 ng per milliliter, 17.0 percent among those with values of 1.1 to
2.0 ng per milliliter, 23.9 percent among those with values of 2.1 to
3.0 ng per milliliter, and 26.9 percent among those with values of 3.1
to 4.0 ng per milliliter. The prevalence of high-grade cancers
increased from 12.5 percent of cancers associated with a PSA level of
0.5 ng per milliliter or less to 25.0 percent of cancers associated
with a PSA level of 3.1 to 4.0 ng per milliliter.

Conclusions Biopsy-detected prostate cancer, including high-grade
cancers, is not rare among men with PSA levels of 4.0 ng per
milliliter or less — levels generally thought to be in the normal
range.

Should the PSA test be replaced with Biopsy for all?