Most prostate cancers missed by raising the upper limit of normal prostate-specific antigen for men in their sixties are clinically significant.

OBJECTIVES: To evaluate the efficacy of applying an age-specific prostate-specific antigen (PSA) reference range to determine whether prostate biopsies are warranted in men 60 to 69 years of age. We estimated the incidence of clinically significant prostate cancer in men in their sixties with PSA levels of 4.01 to 4.50 ng/mL and normal digital rectal examinations (DRE).
METHODS: We reviewed 203 sextant prostate biopsies of men in their sixties with PSA levels of 4.01 to 4.50 ng/mL and normal DRE. Tumors were considered clinically significant if the cancer on biopsy was poorly differentiated (Gleason score of 7 or more), involved more than one core, or included a single focus measuring more than 3 mm.
RESULTS: The positive biopsy rate was 31.5%. More than 80% of the cancers detected satisfied criteria that almost always predict clinically significant cancer. Thus, among men in their sixties with PSA levels of 4.01 to 4.50 ng/mL and normal DRE, the risk of detecting clinically significant cancer on biopsy was approximately 25%.
CONCLUSIONS: Most nonpalpable cancers detected by sextant biopsies in men 60 to 69 years of age with PSA levels of 4.01 to 4.5 ng/mL are clinically significant. Applying an age-specific PSA reference range that increases the upper limit of normal PSA to 4.5 ng/mL results in the failure to detect a substantial number of clinically significant cancers.