PHI combines PSA, free PSA (fPSA), and [-2]Pro-Prostate Specific Antigen in a mathematical formula; [-2]Pro-Prostate Specific Antigen/fPSA X PSA½. [-2]Pro-Prostate Specific Antigen is not yet commercially available in the United States.
The clinical study was a multicenter, double-blind, case-control trial to evaluate PHI in the 2.0 to 10.0 ng/ml PSA range. A final cohort of 892 men from 8 institutions was evaluated between 2003 and 2009. Inclusion criteria included no prior history of CaP, no nodules on DRE, PSA 1.5-11ng/ml, and a prostate biopsy with 6 or more cores with histological interpretation. Over 80% of men were prospectively enrolled. Approximately 80% had an initial prostate biopsy that permitted enrollment, and 18% had repeat biopsies. There were 48.2% of men enrolled with a diagnosis of cancer on their biopsy and 51.8% did not have CaP. The Access 2 Immunoassay Analyzer was used to measure p2PSA, fPSA and PSA. The p2PSA assay is a sandwich immunoassay that measures in pg/ml and samples were run in duplicate for this test. Statistical predictions suggested that at least 295 men without CaP would be needed to detect a 10% difference in specificity between PHI and percent fPSA and 350 men with CaP needed to accurately estimate sensitivity at 95%
They found that PHI and p2PSA were significantly higher in men with CaP than in controls, but fPSA and free to total PSA were lower. Total PSA and age were similar. Ninety-eight percent of men had a 10-core or greater biopsy. Most men were age 60-69. At 95% sensitivity, PHI specificity was 16.0%, compared to 8.4% for F/T PSA, 7.6% for p2PSA, 6.5% for PSA and 3.5% for fPSA. This data rejected the null hypothesis that PHI has no greater specificity that the F/T PSA ratio at 95% sensitivity. The area under the curve (AUC) of CaP detections was significantly greater for PHI (0.703) than for F/T PSA (0.648), fPSA (0.615), p2PSA (0.557), or PSA (0.525). This rejected the secondary null hypothesis that ROC AUC of PHI was equal to that of F/T PSA. Higher PHI values were associated with an increased risk of CaP detection; the relative risk of CaP detection on biopsy was 1.6, 3.0, and 4.7-fold higher at PHI 25.0-34.9, 35.0-54.9, and >55.0 compared with a PHI of <25.0, respectively. A PHI score of >55.0 was associated with a 52.1% probability of CaP. Higher PHI also correlated with higher CaP risk in each age group with up to 54.5% increased risk for ages 60 to 69 years for a PHI >55.0. PHI was able to discriminate Gleason score 7 or higher tumors from lower Gleason score tumors. PHI AUCs exceeded F/T PSA for all prostate volume tertiles.
The investigators conclude that use of PHI may decrease unnecessary prostate biopsies.
Catalona WJ, Partin AW, Sanda MG, Wei JT, Klee GG, Bangma CH, Slawin KM, Marks LS, Loeb S, Broyles DL, Shin SS, Cruz AB, Chan DW, Sokoll LJ, Roberts WL, van Schaik RH, Mizrahi IA
J Urol. 2011 May;185(5):1650-5
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