Christensen E, et al. - Researchers reported how ultra-deep sequencing of cell-free DNA impacts prognosis and predictions in 68 localized advanced bladder cancer patients before and after cystectomy and during chemotherapy. They procured plasma samples (n=656) at diagnosis, during chemotherapy, before cystectomy, and during surveillance; they performed expression profiling for tumor subtype and immune signature analyses. Findings suggest a high prognostic value of circulating tumor DNA (ctDNA) presence at diagnosis prior to chemotherapy. They correctly identified all patients with metastatic relapse during disease monitoring following cystectomy using ctDNA analysis (100% sensitivity, 98% specificity). In addition, they noted the correlation of the dynamics of ctDNA during chemotherapy with disease recurrence in high-risk patients (ctDNA positive before or during treatment), but not with pathologic downstaging. These findings support the feasibility of using ctDNA assessment for early risk stratification, therapy monitoring, and early relapse detection in bladder cancer.