Pro2PSA and PHI
The use of total prostate specific antigen (tPSA) for the early detection of prostate cancer (PCa) is being discussed due to a relatively low specificity and may lead to the detection of a considerable number of low volume, non-aggressive cancers in screening programs. Early detection of prostate cancer (Pca) is a real challenge to reduce morbidity and mortality while avoiding over-diagnosis and over-treatment. The prostate specific antigen (PSA) is characterized by its imperfections justifying the evaluation of new serum or urinary specific markers allowing a better selection of patients at risk of developing aggressive Pca.A molecular isoform of free PSA (fPSA), [-2]proPSA, demonstrated a higher specificity for the detection of PCa as compared with tPSA or f/tPSA. Beckman Coulter recently developed a “prostate health index” (phi) which combines tPSA, fPSA and [-2]proPSA (phi=[-2]proPSA/fPSA)x√tPSA). The clinical performance of phi for the detection of PCa was evaluated in this study.
Methods and results
The patients were included in this study based on the PSA serum concentration between 2.6 ng/mL and 10 ng/mL from consented outpatients, according to the WHO international standard All biopsies were performed according to our internal standardized protocol consisting of 12 cores biopsies or more.
A total of 210 patients , mean age 67 (45-77) with tPSA values between 2.6 – 10 ng/mL (WHO-calibrated) during 2011 and 2012 , underwent ≥12 core biopsies . Serum samples were prepared from blood drawn prior to DRE. The serum concentrations of tPSA, fPSA, and [-2]proPSA were measured with Beckman Coulter immunoassays on Access2 or DxI800 instruments.
Combined evaluation of our cohorts using area under ROC curve (AUC) analysis showed that phi (AUC=0.74) provided significantly (p<0.001) better clinical performance relative to f/tPSA (AUC=0.62) or tPSA (AUC=0.55) in predicting PCa. Significantly higher median values of phi were observed for pts. with Gleason score ≥ 7 (phi=55.0) as compared with pts. with Gleason score < 7 (phi=45.4, p<0.001). The proportion of aggressive PCa (Gleason score ≥ 7) detected was increasing with the phi score. 63% of PCa detected in patients with a phi score > 70 had a Gleason score of ≥ 7. When considering a 90% sensitivity which corresponded to a phi score of 29.3, the majority (75%) of the 10% PCa that were not detected were less aggressive (Gleason score < 7).
The results of this study demonstrate that phi shows a superior clinical performance in detecting PCa in the tPSA range of 2.6 – 10 ng/mL (i.e. 2 – 10ng/mL in traditional calibration) as compared to tPSA or f/tPSA. phi tends to preferentially detect aggressive PCa. PCa missed are mainly Gleason < 7.