Circulating Tumor Cells in Genitourinary Malignancies: An Evolving Path to Precision Medicine

Abstract

Precision medicine with molecularly directed therapeutics is rapidly expanding in all subspecialties of oncology. Molecular analysis and treatment monitoring require tumor tissue, but resections or biopsies are not always feasible due to tumor location, patient safety, and cost. Circulating tumor cells (CTCs) offer a safe, low-cost, and repeatable tissue source as an alternative to invasive biopsies. "Liquid biopsies" can be collected from a peripheral blood draw and analyzed to isolate, enumerate, and molecularly characterize CTCs. While there is deserved excitement surrounding new CTC technologies, studies are ongoing to determine whether these cells can provide reliable and accurate information about molecular drivers of cancer progression and inform treatment decisions. This review focuses on the current status of CTCs in genitourinary (GU) cancer. We will review currently used methodologies to isolate and detect CTCs, their use as predictive biomarkers, and highlight emerging research and applications of CTC analysis in GU malignancies.

Keywords: bladder cancer; circulating tumor cells; liquid biopsy; molecular characterization; prostate cancer.

Figure 1

Circulating tumor cell (CTC) identification and isolation. CTC workflows: immunoaffinity generally utilizes antibody to epithelial cell adhesion molecule and is dependent on EPCAM+ CTCs. Size-based filters are reliant on typically larger size of CTCs. All techniques require some form of staining for cellular identification. Common stains include cytokeratin, 4′,6-diamidino-2-phenylindole (DAPI), leukocyte common antigen (CD45), and others. DEPArray™ enables isolation of individual, intact cells in dielectric cages. Apostream^® allows for antibody-independent capture of CTCs. Epic Sciences™ places unenriched sample on proprietary slide prior to CTC staining and high-resolution scanning. Downstream analysis opportunities are numerous and continue to be explored.