Comparison Between the Four-kallikrein Panel and Prostate Health Index for Predicting Prostate Cancer

Abstract

BACKGROUND The four-kallikrein panel and the Prostate Health Index (PHI) have been shown to improve prediction of prostate cancer compared to prostate-specific antigen (PSA). No comparison between the four-kallikrein panel and PHI has been presented. OBJECTIVE To compare the four-kallikrein panel to PHI for predicting prostate cancer in an independent cohort. DESIGN, SETTING AND PARTICIPANTS Participants were from a population-based cohort of PSA-tested men in Stockholm County. We included men (n=531) with PSA 3–15 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 percent saved biopsies. RESULTS AND LIMITATIONS The four-kallikrein panel showed AUCs of 69.0 when predicting any-grade prostate cancer and 71.8 when predicting high-grade cancer (≥Gleason 7). Similar values were found for PHI: 70.4 and 71.1, respectively. Both models had higher AUC than a base model with PSA and age (p<0.0001 for both); differences between models were not significant. Sensitivity analyses including men with any PSA or a previous biopsy did not materially affect our findings. Using 10% predicted risk of high-grade prostate cancer by the four- kallikrein panel or PHI=39 as cutoff for biopsy saves 29% of performed biopsies to the 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 prostate cancer and high-grade prostate cancer. Both are simple blood tests that can reduce the number of unnecessary biopsies compared to screening with total PSA, representing an important new option to reduce harm.

Emerging biomarkers in the detection and prognosis of prostate cancer

“…More recently, two new studies compared the four-kallikrein panel with PHI and PCA3 score in unscreened and previously screened cohorts, respectively. Nordström et al [79] evaluated the four-kallikrein panel and PHI in a series of 531 men with PSA levels between 3 and 15 μg/L. Both tests performed similarly in the detection of anygrade PCa and high-grade PCa (AUCs: 0.69 and 0.718 for the four-kallikrein panel and 0.704 and 0.711 for PHI).…”

Addressing the need for repeat prostate biopsy: new technology and approaches

“…Data from another study con firmed that these tests have similar diagnostic perfor mance, with use of 4KScore® or PHI resulting in AUCs of 0.69 versus 0.70 when predicting prostate cancer of any grade, respectively and 0.71 for both tests when predict ing highgrade prostate cancer (Gleason score ≥7). 23 The 4KScore® is a unique serumbased marker panel in that it has been used in attempts to address the issue of detecting aggressive prostate cancer.…”

What Can Be Expected from Prostate Cancer Biomarkers A Clinical Perspective

“…Although in comparison with PCA3, 4K test seems to possess a less encouraging predictive value, both of them may improve detection with the European Randomised Study of Screening for Prostate Cancer risk calculator in prescreened men [36]. In another recent study, 4K score was as accurate and specific in predicting PCa and GS ≥7 PCa as PHI [37]. Implementation of 4K test was recently proposed in men >50 years of age in top 10-25% of PSA values to detect metastatic disease as well as to provide biopsy decision support in uncertain cases with elevated PSA [38].…”