Fundamentals of liquid biopsies in metastatic prostate cancer: from characterization to stratification

In this review, we provide an overview of the recent developments and prospects on the applications of blood-based liquid biopsies, including circulating tumor DNA and circulating tumor cells, in metastatic prostate cancer.

Guidelines and consensus statements have been formulated to standardize preanalytical conditions that affect liquid biopsy analysis. Currently, there are four FDA approved assays for the analysis of liquid biopsies and many quantitative and qualitative assays are being developed. Comprehensive analyses of cell-free tumor DNA (ctDNA) and circulating tumor cells (CTCs) demonstrate that they adequately reflect the genomic makeup of the tumor and may thus complement or even replace tumor biopsies. The assessment of genomic aberrations in ctDNA can potentially predict therapy response and detect mechanisms of resistance. CTC count is not only a strong prognosticator in metastatic prostate cancer but can also measure therapy response.

Liquid biopsies may provide a temporal snapshot of the biologic variables that affect tumor growth and progression in metastatic prostate cancer. Liquid biopsies could inform on prognostic, predictive, and response measures. However, prospective clinical trials need to be performed to provide definitive validation of the clinical value of the most advanced assays.