Natural variations in prostate-specific antigen (PSA) levels have been observed, making it difficult to interpret the results of moderately elevated levels (4 to 10 ng per mL) for screening purposes. One study estimated that 15 PSA measurements would be needed to ensure accuracy within 10 percent of the actual mean in most patients. To study PSA variations and determine their implication for prostate cancer screening, Eastham and colleagues analyzed blood samples taken annually over four years in a population of healthy men.

The authors used data and frozen, stored blood samples from the Polyp Prevention Trial. Serum PSA levels were determined in samples from 972 men; free PSA levels also were determined for samples with serum PSA levels between 4 and 10 ng per mL. The following cutoffs were used to define abnormal results: (1) PSA level greater than 4 ng per mL; (2) PSA level greater than 2.5 ng per mL; (3) age-specific PSA levels; (4) free-to-total PSA level ratio lower than 0.25 ng per mL; and (5) PSA velocity higher than 0.75 ng per mL per year.

Using these thresholds, 361 participants (37 percent) met at least one of the criteria for an abnormal result. If the 2.5 ng per mL cutoff were excluded, 245 men (25 percent) would have exceeded one of the four remaining thresholds. Of the men with a normal baseline PSA level, 12 percent would have experienced a subsequent PSA level exceeding 4 ng per mL. Nine percent would have had PSA levels above age-specific criteria, and 10 percent would have had above-threshold free PSA ratios. Of 154 men whose PSA level was elevated before the final visit, 30 percent had a PSA level less than 4 ng per mL at the next visit, 26 percent had subsequent PSA levels below 2.5 ng per mL, 37 percent had subsequent PSA levels below the age-specific level, and 35 percent had subsequent PSA levels below the free PSA level threshold. Between 65 and 83 percent of men whose PSA level returned to normal maintained a normal PSA level on the subsequent annual evaluation.

Even though prostate cancer is detected more frequently with PSA testing, the impact on mortality of diagnosing prostate cancer is unknown. A single abnormal PSA test may not be a sufficient indication for biopsy or immediate repeat testing. The authors conclude that a repeat PSA test after four to six weeks may avoid a costly biopsy. Given the slow growth of prostatic tumors, such a delay should not affect treatment outcomes.