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

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.

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.

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.

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.