Evidence of Benefit
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%.[41,63] 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.
A study specifically tested whether total PSA velocity (tPSAv) improves the accuracy of total PSA level (tPSA) to predict long-term risk of prostate cancer. In the 1974 to 1986 Swedish Malmo Preventive Medicine cardiovascular risk study, 5,722 men younger than 51 years gave two blood samples about 6 years apart. Four thousand nine hundred-seven of the archived plasma samples were analyzed for tPSA. Prostate cancer was subsequently diagnosed in 443 (9%) of the men via the Swedish National Cancer Registry through December 31, 2003. Cox proportional hazards regression was used to evaluate tPSA and tPSAv as predictors of prostate cancer. Predictive accuracy was assessed by the concordance index (similar to the area under the receiver operating characteristic).