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
. 2019 Oct;37(10):672-677.
doi: 10.1016/j.urolonc.2019.07.010. Epub 2019 Aug 2.

Developing an effective strategy to improve the detection of significant prostate cancer by combining the 4Kscore and multiparametric MRI

Karim Marzouk  1 , Behfar Ehdaie  2 , Emily Vertosick  3 , Stephen Zappala  4 , Andrew Vickers  5
Affiliations

Developing an effective strategy to improve the detection of significant prostate cancer by combining the 4Kscore and multiparametric MRI

Karim Marzouk et al. Urol Oncol. 2019 Oct.

Abstract

Objectives: Recent years have seen the development of biomarkers and imaging technologies designed to improve the specificity of PSA. Widespread implementation of imaging technologies, such as mp-MRI raises considerable logistical challenges. Our objective was to evaluate a biopsy strategy that utilizes selective mp-MRI as a follow-up test to biomarkers to improve the detection of significant prostate cancer.

Methods and materials: We developed a conceptual approach based on the risk calculated from the 4Kscore using results from the US prospective validation study, multiplied by the likelihood ratio of mp-MRI from the PROMIS trial. The primary outcome was Gleason grade ≥ 7 (grade group ≥ 2) cancer on biopsy. Using decision curve analysis, the net benefit was determined for our model and compared with the use of the 4Kscore and mp-MRI independently at various thresholds for biopsy.

Results: For a cut-point of 7.5% risk of high-grade disease, patients with <5% risk from a blood marker would not have risk of significant prostate cancer sufficiently increased by a positive mp-MRI to warrant biopsy; comparably, patients with a risk >23% would not have risk sufficiently reduced by a negative imaging study to forgo biopsy. From the 4Kscore validation study, 46% of men considered for biopsy in the US have risks 5% to 23%. Net benefit was highest for the combined strategy, followed by 4Kscore alone.

Conclusions: Selective mp-MRI in men with intermediate scores on a secondary blood test results in a biopsy strategy that is more scalable than mp-MRI for all men with elevated PSA. Prospective validation is required to demonstrate if the predicted properties of combined blood and imaging testing are empirically confirmed.

Keywords: 4Kscore; Magnetic resonance imaging; Prostate biopsy; Prostate cancer.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures

Dr Andrew Vickers is a named co-inventor on US patent number: 9,672,329 for a statistical method for predicting the result of a prostate cancer biopsy. The patent is the algorithm used in the 4Kscore. He receives royalties for its commercialize use by Opko Diagnostics. Dr Vickers also serves on Opko’s advisory board and receives stock options from Opko. Dr Stephen Zappala has stock options in Opko.

The remaining authors have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Prostate biopsy decision pathway by estimated risk of clinically significant prostate cancer
See this image and copyright information in PMC

References

    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. 2015;68:464–470. - PubMed
    1. Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet (London, England). 2017. - PubMed
    1. Konety B, Zappala SM, Parekh DJ, et al. The 4Kscore® Test Reduces Prostate Biopsy Rates in Community and Academic Urology Practices. Rev Urol. 2015;17:231–240. - PMC - PubMed
    1. Vickers AJ, Elkin EB. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making. 2006;26:565–574. - PMC - PubMed
    1. Vargas HA, Akin O, Franiel T, et al. Diffusion-weighted endorectal MR imaging at 3 T for prostate cancer: tumor detection and assessment of aggressiveness. Radiology. 2011;259:775–784. - PMC - PubMed

Publication types

MeSH terms