Liquid Biopsy Landscape in Patients with Primary Upper Tract Urothelial Carcinoma

Simple Summary The standard of care for patients diagnosed with upper tract urothelial carcinoma (UTUC) is surgery. However, the current standard tools for the diagnosis and preoperative risk stratification of primary UTUC leave much to be desired. Using a simple blood sample, we can detect rare events, such as circulating tumor cells (CTCs) and large extracellular vesicles (LEVs), which may reveal biomarkers indicative of disease and provide insight into progression. This study demonstrates a wide variety of CTCs and LEVs that are identifiable in the blood of patients with UTUC at higher counts compared to normal donors. The data presented indicate that a blood-based liquid biopsy can detect UTUC and help guide clinical decisions. Urothelial carcinomas (UCs) are a broad and heterogeneous group of malignancies, with the prevalence of upper tract urothelial carcinoma (UTUC) being rare, accounting for only 5-10% of total malignancies. There is a need for additional toolsets to assist the current clinical paradigm of care for patients with UTUC. As a non-invasive tool for the discovery of cancer-related biomarkers, the liquid biopsy has the potential to represent the complex process of tumorigenesis and metastasis. Herein, we show the efficacy of the liquid biopsy as a source of biomarkers for detecting UTUC. Using the third-generation high-definition single-cell assay (HDSCA3.0) workflow, we investigate liquid biopsy samples collected from patients with UTUC and normal donors (NDs) to provide critical information regarding the molecular and morphological characteristics of circulating rare events. We document several important findings from the liquid biopsy analysis of patients diagnosed with UTUC prior to surgery: (1) Large extracellular vesicles (LEVs) and circulating tumor cells (CTCs) are detectable in the peripheral blood. (2) The rare-event profile is highly heterogeneous. (3) Clinical data elements correlate with liquid biopsy analytes. Overall, this study provides evidence for the efficacy of the liquid biopsy in understanding the biology of UTUC with the future intent of informing clinical decision making, ultimately improving patient outcomes.

Automated summary

Liquid biopsy can detect circulating tumor cells and large extracellular vesicles in patients with upper tract urothelial carcinoma, providing important information for understanding the biology of the disease and potentially improving patient outcomes.