Elsevier

European Urology

Volume 68, Issue 1, July 2015, Pages 139-146
European Urology

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

https://doi.org/10.1016/j.eururo.2014.08.010Get rights and content

Abstract

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.

Introduction

Numerous studies have addressed the limited diagnostic accuracy of a patient's prostate-specific antigen (PSA) level and yet it remains the only widely adopted biomarker for prostate cancer (PCa) [1], [2], [3], [4].

Although sensitivity to detect increased risk of metastasis or death from PCa many years later may be unique [5], insufficient test specificity drives frequent prostate biopsies and a large proportion of benign biopsy specimens. Several additional biomarkers have been suggested, none of which have reached widespread clinical use. However, a few blood-based biomarkers have proved promising.

The Prostate Health Index (PHI) is an algorithm including the PSA isoform [−2]proPSA with total and free PSA. It has been demonstrated to increase predictive performance in several ethnically diverse cohorts for predicting PCa at biopsy or in radical prostatectomy specimens [6], [7], [8], [9], [10], [11].

Several other human kallikrein-related peptidases have been explored, and a four-kallikrein panel including kallikrein-related peptidase 2 (hK2), intact PSA, and free and total PSA has repeatedly been shown to predict prostate biopsy outcome in primarily European men with an elevated PSA level and to save a substantial number of biopsies [12], [13], [14], [15], [16].

The four-kallikrein (4K) panel and PHI represent improved tests for PCa that potentially can be of widespread clinical use. However, no study has compared the performance of these tests.

Section snippets

Study design

This observational study, using prospectively collected data, included men with blood samples drawn before a prostate biopsy resulting in cancer diagnosis (cases) or benign findings (controls). The study was designed to compare the diagnostic performance for predicting PCa using a base model containing total PSA value and age, PHI, and the 4K panel, respectively.

Study population

Men referred for PSA testing in laboratories in Stockholm County between 2010 and 2012 were invited to the population-based cohort

Results

Clinical characteristics of the study population are listed in Table 1 and Fig. 1. We identified 531 participants who had not undergone biopsy previously and whose PSA levels were between 3 and 15 ng/ml (271 cases and 260 controls). Of the cases, 134 (49%) were characterized as Gleason grade ≥7. Cases were older than controls (mean age: 66.0 yr vs 64.6 yr; p = 0.04). Concentrations of free PSA and [−2]proPSA differed significantly between groups (p < 0.001 and p = 0.038, respectively).

Discussion

We have compared the performance of two predictive models—PHI and a 4K panel—with each other and with a base model when applied to men who had not previously undergone a prostate biopsy with intermediately increased PSA level. We found that both PHI and the 4K panel increased predictive accuracy compared with the base model and that the PHI model and the 4K panel performed similarly for predicting both high-grade disease and all cancer.

Lilja and colleagues have repeatedly demonstrated that the

Conclusions

The 4K 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.

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