Session: PD46: Bladder Cancer: Upper Tract Transitional Cell Carcinoma II
PD46-01: Detection of individualized mutations and monitoring of postoperative recurrence using circulating tumor DNA in patients with upper tract urothelial carcinoma
Introduction: Upper tract urothelial carcinoma (UTUC) is an aggressive disease which have high recurrence after surgery. Current standard methods for the diagnosis and detection of recurrence are invasive or low sensitivity. Circulating tumor DNA (ctDNA) analysis using digital polymerase chain reaction (dPCR) has demonstrated promising results for monitoring as recurrence in several cancers. The aim of this study was to evaluate the validity of plasma and urinary ctDNA as a tumor biomarker for UTUC among a perioperative period. Methods: This study included 23 patients who underwent radical nephroureterectomy (RNU) diagnosed as UTUC from January 2019 to December 2020. In each patient, whole exome sequencing (WES) of tumor DNA and corresponding peripheral blood mononuclear cell (PBMC) DNA were performed by next generation sequencer (NGS). To investigate ctDNA by dPCR analysis, we selected tumor specific gene mutations included in our original primer-probe library. We also collected plasma and urine ctDNA from each patient. Longitudinal variant allele frequency (VAF) of ctDNA were plot on a pre- and post-operative period. Results: The median age was 71 years old (range 57-82). 13 cases were renal pelvis cancer, and 10 cases were ureteral cancer. Most frequently mutated genes revealed by tumor DNA analysis using NGS were TERT (43%), KMT2D (35%), TTN (30%), FGFR3 (26%), and TP53 (26%). 17 cases (74%) could be performed ctDNA monitoring by our primer-probe library. Tumor specific mutations were detected in preoperative samples in 15 cases. Tumor specific mutations were not detected in two cases who were ypT0 due to neoadjuvant chemotherapy. Six cases experienced recurrence after RNU, five of which showed increase of VAFs of ctDNA. Conclusions: ctDNA analysis using dPCR could detect tumor specific mutations in majority of patients with UTUC. Individualized ctDNA monitoring could be a useful biomarker for postoperative recurrence. SOURCE OF Funding: None
