Challenges in Standardizing ctDNA-guided MRD Testing in MIBC

In this segment, Dr. Thomas Powles opened the discussion on the challenges of standardizing ctDNA-guided MRD testing across cancer types, emphasizing that while panel-based assays are established in colorectal, lung, and breast cancers, urothelial cancer benefits more from personalized tumor-informed assays that track patient-specific mutations for superior specificity and fewer false positives. He highlighted the Signatera assay as the most validated approach in the perioperative setting, where accuracy is critical. Panelists expanded on key assay attributes—particularly sensitivity, which continues to improve through longitudinal sampling and new whole-genome designs tracking up to 64 variants. They explained that broader variant coverage increases detection confidence, using a “raindrop” analogy to describe capturing molecular signals across multiple genomic sites. Also, panelists noted current limitations, including poor ctDNA detection in CNS, peritoneal, and small lung lesions, while liver and bone metastases tend to shed ctDNA more reliably.