In this prospective cohort study, peripheral blood samples were collected from 28 primary UTUC patients before and after surgery with curative intent and analyzed to detect CTCs and oncosomes.5 The cohort included a combination of non-muscle-invasive and muscle-invasive UTUCs, with the majority being high grade. Eight categories of CTCs and four categories of oncosomes were assessed using third-generation comprehensive high-definition single-cell assay (HDSCA3.0) (Figure 1).
Figure 1: Workflow of sample collection, processing, and analysis.
Comparing preoperative samples and normal donors, significant differences in specific rare analytes were detected (Figure 2-A). In terms of pathologic staging, patients with pT3 compared to pT1 had significantly higher preoperative levels of total- and D|V cells. Within a median 6 months following surgery, total-, CK-, and CK|V oncosomes, as well as D-, D|V-, and D|V|CD cells were decreased significantly compared to preoperative levels (Figure 2-B). Lastly, patients with >1.95 preoperative CK|V oncosomes and those with >4.18 D|CK|V cells had a worse recurrence-free survival compared to other patients (Figure 2-C and D).
Figure 2: Liquid biopsy biomarkers in (A) UTUCs before surgery vs normal donors, and (B) UTUC before and after surgery; (C and D) recurrence-free survival analyses.
These findings provide promising evidence for the possible clinical utility of blood-based liquid biopsy biomarkers in the diagnosis and preoperative risk-stratification of patients with UTUC. When combined with current clinical practices, liquid biopsy can optimize decision-making, such as need for neoadjuvant chemotherapy and/or the eligibility for nephron-sparing procedures compared to radical surgery. In addition, liquid biopsy may serve as a non-invasive method in the surveillance of UTUC patients after surgery. This could be particularly important for individuals undergoing nephron-sparing procedures who require regular ureteroscopies. A larger sample size study with additional follow-up samples and a more comprehensive genomic analysis, including ctDNA, is necessary to validate the findings of our study.
Written by: Alireza Ghoreifi, MD, and Hooman Djaladat, MD, MS
Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
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