ProPSA and the Prostate Health Index as predictive markers for aggressiveness in low-risk prostate cancer—results from an international multicenter study

5074 Background: Although prostate-specific antigen (tPSA) screening reduced prostate cancer (PCa) mortality recent recommendations do not endorse PSA-screening due to overdiagnosis and overtreatment and the resulting harm afflicted to patients. Screening studies showed the maximum benefit in young men < 65 years of age. tPSA and percent free PSA (%fPSA) lack specifity in the diagnosis of PCa. [-2]proPSA and the prostate health index (phi) improved this diagnostic specifity. Markers to diagnose clinicaly relevant cancers in young men are needed. Methods: The clinical performance of [-2]proPSA and phi was evaluated in a multicenter study. A total of 1362 patients scheduled for initial or repeated prostate biopsy (668 with, 694 without PCa, each ≥ 10 core biopsies) were recruited in 4 different sites based on PSA level 1.6 – 8.0 ng/mL WHO-calibrated (2-10 ng/mL classically calibrated). Serum samples taken prior to digital rectal examination (DRE) were measured for the concentration of tPSA, fPSA and [-2]proPSA with Beckman Coulter immunoassays on Access 2 or DxI800 instruments. Phi was calculated as [-2]proPSA/fPSA*√tPSA. Results: In univariate analysis [-2]proPSA/fPSA (%[-2]proPSA) and phi were the best predictors of PCa detection in patients at initial biopsy (AUC: 0,72 and 0,73) and repeated biopsy (AUC: 0,74 and 0,74). Analysis of the data for men ≤ 65 years of age (n=593) showed that %[-2]proPSA and phi significantly improved PCa dectection (AUC: 0,72 and 0,73) as compared with tPSA (AUC: 0,54) or %fPSA (AUC: 0,62). In the detection of significant PCa (based on PRIAS criteria) %[-2]proPSA and phi demonstrated the best performance in the whole cohort and in young men (≤ 65) years as well (AUC 0,68 and 0,73). Conclusions: This multicenter study showed that [-2]proPSA and phi have a superior clinical performance in detecting PCa in the PSA range of 2-10 ng/mL compared with tPSA and %fPSA at initial and repeated biopsies. This superiority is maintained for the detection of PCa in young men (≤ 65 years of age).

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Multicenter Evaluation of [−2]Proprostate-Specific Antigen and the Prostate Health Index for Detecting Prostate Cancer

Clinical Chemistry ◽

10.1373/clinchem.2012.195784 ◽

2013 ◽

Vol 59 (1) ◽

pp. 306-314 ◽

Cited By ~ 75

Author(s):

Carsten Stephan ◽

Sébastien Vincendeau ◽

Alain Houlgatte ◽

Henning Cammann ◽

Klaus Jung ◽

...

Keyword(s):

Prostate Cancer ◽

Gleason Score ◽

Multicenter Study ◽

Clinical Performance ◽

Specific Antigen ◽

Digital Rectal Examination ◽

Health Index ◽

Free Psa ◽

Prostate Health Index ◽

Prostate Health

BACKGROUND Total prostate-specific antigen (tPSA) is flawed for prostate cancer (PCa) detection. [−2]proprostate-specific antigen (p2PSA), a molecular isoform of free PSA (fPSA), shows higher specificity compared with tPSA or percentage of free PSA (%fPSA). The prostate health index (Phi), a measure based on p2PSA and calculated as p2PSA/fPSA × √tPSA, was evaluated in a multicenter study for detecting PCa. METHODS A total of 1362 patients from 4 different study sites who had tPSA values of 1.6–8.0 μg/L (668 patients with PCa, 694 without PCa) underwent ≥10 core biopsies. Serum concentrations of tPSA, fPSA (both calibrated against a WHO reference material), and p2PSA were measured on Access2 or DxI800 analyzers (Beckman Coulter). RESULTS The percentage ratio of p2PSA to fPSA (%p2PSA) and Phi were significantly higher in all PCa subcohorts (positive initial or repeat biopsy result or negative digital rectal examination) (P < 0.0001) compared with patients without PCa. Phi had the largest area under the ROC curve (AUC) (AUC = 0.74) and provided significantly better clinical performance for predicting PCa compared with %p2PSA (AUC = 0.72, P = 0.018), p2PSA (AUC = 0.63, P < 0.0001), %fPSA (AUC = 0.61) or tPSA (AUC = 0.56). Significantly higher median values of Phi were observed for patients with a Gleason score ≥7 (Phi = 60) compared with a Gleason score <7 (Phi = 53; P = 0.0018). The proportion of aggressive PCa (Gleason score ≥7) increased with the Phi score. CONCLUSIONS The results of this multicenter study show that Phi, compared with tPSA or %fPSA, demonstrated superior clinical performance in detecting PCa at tPSA 1.6–8.0 μg/L (i.e., approximately 2–10 μg/L in traditional calibration) and is better able to detect aggressive PCa.

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