IBCN 2022: Genome-Wide Circulating Tumor DNA for Monitoring Treatment Response and Metastatic Relapse in Bladder Cancer

(UroToday.com) Approximately 45% of patients with localized muscle-invasive bladder cancer treated with neoadjuvant chemotherapy followed by radical cystectomy will develop recurrence, thus making biomarkers for early detection of minimal residual disease a critical unmet need. Tumor informed detection of mutations in cell-free DNA (cfDNA) has shown promising results in that respect. In this study presented by Dr. Nordentoft, a whole-genome sequencing (WGS) approach to circulating tumor DNA (ctDNA) was applied for sensitive monitoring of Minimal Residual Disease (MRD).

67 MIBC patients undergoing NAC/RC were accrued. Longitudinal plasma samples during and after RC and following implementation of salvage therapy were procured and cfDNA was extracted. WGS of tumor/germline pairs and plasma cfDNA were performed to facilitate the detection of genome wide alterations and quantification of ctDNA. Tumor-informed WGS model were constructed by integrating genome-wide mutation and copy number variation data coupled with advanced signal processing. Patient-specific somatic variants were used for detection and measuring ctDNA levels by WGS. Post-RC ctDNA analysis identified tumor recurrence with 76% sensitivity and 96% specificity and provided a median lead time over radiographic imaging of 161 days. ctDNA clearance following RC was also prognostic associated with improved recurrence-free (p<0.0001) and overall survival (p<0.0001). Furthermore, ctDNA clearance during NAC was also associated with recurrence-free survival (p=0.0089).

Presented by: Iver Nordentoft, MSc, PhD, Department of Clinical Medicine, Department of Molecular Medicine,  Aarhus University

Written by: Roger Li, Urologic Oncologist, Moffitt Cancer Center, during the International Bladder Cancer Network Annual Meeting, September 28-October 1, 2022, Barcelona, Spain