Prostate Cancer Screening (PDQ®): Screening - Health Professional Information [NCI] - Evidence of Benefit
Summary of First Four Prostate, Lung, Colorectal, and Ovarian Screening Roundsa continued...
The third-generation (ultrasensitive) PSA test is an enzyme immunometric assay intended strictly (or solely) as an aid in the management of prostate cancer patients. The clinical usefulness of this assay as a diagnostic or screening test is unproven.[60,61]
Because larger prostates caused by increased amounts of transition-zone hyperplasia are known to be associated with higher serum PSA levels, reports have suggested indexing PSA to gland volume, using a measure known as PSA density. PSA density is defined as serum PSA divided by gland volume. Generally, ultrasound is used to measure gland volume. While early studies suggested that this measure may discriminate between patients with cancer and those with benign disease, subsequent evaluations have failed to confirm any clinically useful association.[63,64]
PSA density of the transition zone
PSA density of the transition zone (serum PSA divided by the volume of the transition zone) has been suggested to better adjust for benign sources of PSA. One study prospectively evaluated 559 men with PSA levels between 4.0 ng/mL and 10.0 ng/mL. A total of 217 of these men were ultimately found to have prostate cancer; of all PSA variants analyzed, percent-free PSA and PSA density of the transition zone were found to have the best predictive value (area under the receiver operator curve values of 0.78 and 0.83). Another study also found that PSA density of the transition zone had superior performance characteristics. In this study of 308 volunteers undergoing first-time screening, it was reported that the combination of percent-free PSA (<20%) and PSA density of the transition zone resulted in elimination of 54.2% of biopsies that ultimately proved to be benign.
Many series have noted that PSA levels increase with age, such that men without prostate cancer will have higher PSA values as they grow older. One study examined the impact of the use of age-adjusted PSA values during screening and estimated that it would reduce the false-positive screenings by 27% and overdiagnosis by more than 33% while retaining 95% of any survival advantage gained by early diagnosis. While age adjustment tends to improve sensitivity for younger men and specificity for older men, the trade-off in terms of more biopsies in younger men and potentially missed cancers in older men has prevented uniform acceptance of this approach.
A study using frozen serum from 18 patients concluded that an annual rise of PSA level of 0.8% ng/mL warranted a prostate biopsy. In a follow-up study that used serum collected serially from men without known prostate cancer (two groups with benign prostatic hyperplasia, one diagnosed by histology and the other clinically, both with PSA levels no higher than 10 ng/mL, and a third group with no more than one PSA exceeding 10 ng/mL), it was reported that averaging three PSA changes measured at 2-year intervals could be useful for cancer discrimination, while changes measured at 3-month or 6-month intervals were volatile and nonspecific, perhaps because of a biologic fluctuation of PSA that may be as high as 30%.[42,69] One study followed 1,249 men screened by PSA and concluded that patients with a 20% annual increase in their PSA level should undergo further evaluation.