Blood-based liquid biopsies for prostate cancer: clinical opportunities and challenges

Abstract

Liquid biopsy has been established as a powerful, minimally invasive, tool to detect clinically actionable aberrations across numerous cancer types in real-time. With the development of new therapeutic agents in prostate cancer (PC) including DNA repair targeted therapies, this is especially attractive. However, there is unclarity on how best to screen for PC, improve risk stratification and ultimately how to treat advanced disease. Therefore, there is an urgent need to develop better biomarkers to help guide oncologists' decisions in these settings. Circulating tumour cells (CTCs), exosomes and cell-free DNA/RNA (cfDNA/cfRNA) analysis, including epigenetic features such as methylation, have all shown potential in prognostication, treatment response assessment and detection of emerging mechanisms of resistance. However, there are still challenges to overcome prior to implementing liquid biopsies in routine clinical practice such as preanalytical considerations including blood collection and storage, the cost of CTC isolation and enrichment, low-circulating tumour content as a limitation for genomic analysis and how to better interpret the sequencing data generated. In this review, we describe an overview of the up-to-date clinical opportunities in the management of PC through blood-based liquid biopsies and the next steps for its implementation in personalised treatment guidance.

Fig. 1. Liquid biopsy in prostate cancer: tumour features, clinical utility and challenges.

a Example of actively proliferating prostate cancer metastatic sites. b Potential differential tumour material release with the highest contribution from the liver metastasis followed by the bone and restricted release from the brain due to the blood/brain barrier. c Circulating tumour material features that can be isolated and analysed from blood. d Potential clinical utility of liquid biopsy analysis in prostate cancer management from diagnosis to death and listing the most suitable methods for analysis in each set to overcome the respective sensitivity requirements. ctDNA circulating tumour DNA, miRNA microRNA, CTCs circulating tumour cells, tNGS targeted next-generation sequencing, WGS whole-genome sequencing, ddPCR droplet digital PCR, PC prostate cancer, HSPC hormone-sensitive prostate cancer, CRPC castration-resistant prostate cancer.