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BACKGROUND: The four-kallikrein panel and the Prostate Health Index (PHI) have been shown to improve prediction of prostate cancer (PCa) compared with prostate-specific antigen (PSA). No comparison of the four-kallikrein panel and PHI has been presented. OBJECTIVE: To compare the four-kallikrein panel and PHI for predicting PCa in an independent cohort. DESIGN, SETTING, AND PARTICIPANTS: Participants were from a population-based cohort of PSA-tested men in Stockholm County. We included 531 men with PSA levels between 3 and 15 ng/ml undergoing first-time prostate biopsy during 2010-2012. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Models were fitted to case status. We computed calibration curves, the area under the receiver-operating characteristics curve (AUC), decision curves, and percentage of saved biopsies. RESULTS AND LIMITATIONS: The four-kallikrein panel showed AUCs of 69.0 when predicting any-grade PCa and 71.8 when predicting high-grade cancer (Gleason score ≥7). Similar values were found for PHI: 70.4 and 71.1, respectively. Both models had higher AUCs than a base model with PSA value and age (p<0.0001 for both); differences between models were not significant. Sensitivity analyses including men with any PSA level or a previous biopsy did not materially affect our findings. Using 10% predicted risk of high-grade PCa by the four-kallikrein panel or PHI of 39 as cut-off for biopsy saved 29% of performed biopsies at a cost of delayed diagnosis for 10% of the men with high-grade cancers. Both models showed limited net benefit in decision analysis. The main study limitation was lack of digital rectal examination data and biopsy decision being based on PSA information. CONCLUSIONS: The four-kallikrein panel and PHI similarly improved discrimination when predicting PCa and high-grade PCa. Both are simple blood tests that can reduce the number of unnecessary biopsies compared with screening with total PSA, representing an important new option to reduce harm. PATIENT SUMMARY: Prostate-specific antigen screening is controversial due to limitations of the test. We found that two blood tests, the Prostate Health Index and the four-kallikrein panel, performed similarly and could both aid in decision making among Swedish men undergoing a prostate biopsy.

Original publication




Journal article


Eur Urol

Publication Date





139 - 146


Biomarkers, Kallikrein-related peptidases, Prostate-specific antigen, Prostatic neoplasms, Age Factors, Aged, Area Under Curve, Biomarkers, Tumor, Cohort Studies, Decision Support Techniques, Humans, Kallikreins, Logistic Models, Male, Middle Aged, Prospective Studies, Prostate-Specific Antigen, Prostatic Neoplasms, Protein Precursors, ROC Curve, Sensitivity and Specificity, Tissue Kallikreins