Early prognostication of clinically significant prostate cancer from blood samples via the detection of ultrasound induced release of circulating-tumour cell-specific microRNA combined with clinical imaging

The overdiagnosis of clinically-significant prostate cancer is a widespread issue stemming from the lack of specificity of currently utilized metrics such as prostate specific antigen measurements. These markers can fluctuate due to a myriad of benign conditions, resulting in overdiagnosis and over-treatment which places an excessive burden on already strained healthcare systems. As such, we present a novel liquid biopsy assay for the detection of circulating-tumour-cells that demonstrates improved sensitivity and specificity for clinically-significant prostate cancer over existing metrics. As circulating-tumour-cells are often difficult to detect directly due to their sparsity, an indirect approach is utilized in which mononuclear cells isolated from a blood draw are exposed to ultrasound in the presence of microbubbles; this leads to the formation of transient microscopic pores on cell membranes allowing for the release of microRNA. The prediction model developed from these biomarker release metrics, in conjunction with clinical data and PSA measurements, resulted in an AUROC of 0.86, greatly over-performing PSA tests alone (AUROC of 0.78 in our study, 0.67 in literature). Additionally, incorporating mpMRI imaging data improved the AUROC to 0.92. The ex vivo and minimally invasive nature of our assay enables facile integration into existing clinical workflows and may provide a drastically improved triage criterion for follow-up diagnostics.