Developing an Effective Strategy to Improve the Detection of Significant Prostate Cancer by Combining the 4Kscore and Multiparametric MRI

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.