[-2]Proenzyme Prostate Specific Antigen is More Accurate Than Total and Free Prostate Specific Antigen in Differentiating Prostate Cancer From Benign Disease in a Prospective Prostate Cancer Screening Study

Abstract

Purpose Due to the limited specificity of prostate-specific antigen (PSA) for prostate cancer (CaP) screening, there is an ongoing search for adjunctive biomarkers. Retrospective studies have suggested that an isoform of proenzyme PSA called [−2] proPSA (p2PSA) may enhance the specificity of PSA-based screening. The objective of our study was to examine the utility of p2PSA in a prospective CaP screening study. Materials and Methods From a population of 2034 men undergoing CaP screening, we examined the relationship between p2PSA and CaP detection. Specifically, we compared the utility of total PSA, the ratio of free PSA (fPSA) to total PSA (%fPSA), the ratio of p2PSA to fPSA (%p2PSA) and a formula combining PSA, fPSA and p2PSA (called Beckman Coulter prostate health index or phi®) to predict CaP among men from the study undergoing prostate biopsy with PSA levels of 2.5–10 ng/ml and non-suspicious digital rectal examination (DRE). Results Despite similar total PSA levels (p=0.88), both %fPSA (p=0.02) and %p2PSA (p=0.0006) distinguished between positive and negative biopsy results. On receiver operating characteristic (ROC) analysis, %p2PSA (AUC 0.76) outperformed both PSA (AUC 0.50) and %fPSA (AUC 0.68) for differentiating between CaP and benign disease. Setting the sensitivity at 88.5%, p2PSA led to a substantial improvement in specificity, positive and negative predictive values. The Beckman Coulter phi® (AUC 0.77) had the best overall performance characteristics. Conclusions This is the first prospective study to demonstrate that p2PSA provides improved discrimination between CaP and benign disease in screened men with PSA levels from 2.5 to 10 ng/ml and negative DRE.

The percentage of prostate‐specific antigen (PSA) isoform [–2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged ≤65 years

“…Based on p2PSA, the 'Prostate Health Index' (PHI) has been developed (a formula that includes p2PSA, f-PSA and t-PSA) and PHI was shown to improve the diagnostic accuracy for prostate cancer [14,15].…”

PSA, PSA derivatives, proPSA and prostate health index in the diagnosis of prostate cancer

“…[43,44] ProPSA, and Prostate Health Index (PHI) It is a mathematical equation demonstrating probability of prostate cancer This equation is formulated as p2PSA/fPSA)/ [14] Higher PHI values have been associated with increased probability of prostate cancer. Le et al [45] performed ROC analyses, and demonstrated the highest performance for phi among other tumor markers with an AUC of 0.77. With a specificity of 33%, phi reached nearly 2-fold specificity of fPSA/tPSA.…”

A pilot study evaluating serum pro-prostate-specific antigen in patients with rising PSA following radical prostatectomy

“…Sokoll et al have demonstrated that the ratio of 2pPSA to fPSA (%2pPSA) is capable of improving prostate cancer detection and is correlated with the risk of aggressive disease (13). Le et al have shown that the use of %2pPSA or the combination of 2pPSA, PSA and fPSA in the so-called 'prostate health index' (PHI) proved superior in discriminating between prostate cancer and benign disease in males with a total PSA of 2.5-10 ng/ml and negative digital rectal examination (14). These results have been confirmed in a recent multicenter study conducted in 892 subjects with PSA values between 2 and 10 ng/ml (15).…”