Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2018 Jun;199(6):1470-1474.
doi: 10.1016/j.juro.2018.01.070. Epub 2018 Jan 31.

Value of Intact Prostate Specific Antigen and Human Kallikrein 2 in the 4 Kallikrein Predictive Model: An Individual Patient Data Meta-Analysis

Andrew Vickers  1 , Emily A Vertosick  2 , Daniel D Sjoberg  2 , Freddie Hamdy  3 , David Neal  3 , Anders Bjartell  4 , Jonas Hugosson  5 , Jenny L Donovan  6 , Arnauld Villers  7 , Stephen Zappala  8 , Hans Lilja  2
Affiliations
Meta-Analysis

Value of Intact Prostate Specific Antigen and Human Kallikrein 2 in the 4 Kallikrein Predictive Model: An Individual Patient Data Meta-Analysis

Andrew Vickers et al. J Urol. 2018 Jun.

Abstract

Purpose: The 4 kallikrein panel, commercially available as the 4Kscore®, is a statistical model that has been shown to accurately predict Gleason Grade Group 2 or greater (high grade) cancer on biopsy and the long-term risk of distant prostate cancer metastases. The panel includes 2 novel markers, namely intact prostate specific antigen and hK2. It has been questioned whether these 2 additional markers add discrimination to the clinical predictors of patient age, digital rectal examination and prior biopsy, and the established molecular markers total and free prostate specific antigen.

Materials and methods: We performed an individual patient data meta-analysis of published studies in which the 4 kallikrein panel was measured in men undergoing prostate biopsy. We assess the improvement in discrimination associated with including intact prostate specific antigen and hK2 along with total and free prostate specific antigen in the statistical model.

Results: Included in analysis were 14,510 men from a total of 10 studies. The fixed effects meta-analytical estimate of the discrimination of the model without intact prostate specific antigen and hK2 was 0.742 (95% CI 0.727-0.756) compared to 0.813 (95% CI 0.801-0.825) for the full kallikrein model. The 95% CIs did not overlap and the difference in discrimination was highly statistically significant (0.069, 95% CI 0.057-0.080, p <0.0001). Intact prostate specific antigen (increase in discrimination 0.059, 95% CI 0.050-0.069) and hK2 (increase in discrimination 0.024, 95% CI 0.020-0.029, each p <0.0001) added independently to the model.

Conclusions: The clinical value of the panel could not be replicated using data readily available to urologists without measuring intact prostate specific antigen and hK2.

Keywords: digital rectal examination; early detection of cancer; kallikreins; prostate-specific antigen; prostatic neoplasms.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

HL hold patents on assays for free PSA, intact PSA, and HK2. AV and HL are named on a patent for a statistical method to detect prostate cancer. The method has been commercialized by OPKO Health. AV and HL receive royalties from sales of the test. HL has stock and AV has stock options in OPKO Health. MJR is a member of the advisory board of OPKO Health. SZ is a Consultant with stock options at OPKO Health.

Figures

Figure 1.
Figure 1.
Forest plot for the difference in AUC between models with and without hK2 and intact PSA
See this image and copyright information in PMC

Comment in

  • Editorial Comment.
    Klein EA. Klein EA. J Urol. 2018 Jun;199(6):1474. doi: 10.1016/j.juro.2018.01.088. Epub 2018 Mar 9. J Urol. 2018. PMID: 29526519 No abstract available.

References

    1. Lamy PJ, Allory Y, Gauchez AS et al.: Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic Review. Eur Urol Focus, 2017 - PubMed
    1. McDonald ML, Parsons JK: 4-Kallikrein Test and Kallikrein Markers in Prostate Cancer Screening. Urol Clin North Am, 43: 39, 2016 - PubMed
    1. Parekh DJ, Punnen S, Sjoberg DD et al.: A Multi-institutional Prospective Trial in the USA Confirms that the 4Kscore Accurately Identifies Men with High-grade Prostate Cancer. European Urology, 68: 464, 2015 - PubMed
    1. Vickers A, Vertosick EA, Sjoberg DD et al.: Properties of the 4-Kallikrein Panel Outside the Diagnostic Gray Zone: Meta-Analysis of Patients with Positive Digital Rectal Examination or Prostate Specific Antigen 10 ng/ml and Above. J Urol, 197: 607, 2017 - PMC - PubMed
    1. Punnen S, Freedland SJ, Polascik TJ et al.: A Multi-institutional Prospective Trial in the Veterans Affairs Health System confirms the 4Kscore maintains its Predictive value among African American Men. J Urol, 2017 - PubMed

Publication types