The FDA approved Genentech’s Tecentriq (atezolizumab) and Tecentriq Hybreza as adjuvant therapy for muscle-invasive bladder cancer (MIBC) patients who are ctDNA-positive after cystectomy based on Natera’s Signatera CDx MRD assay. Regulators also authorized Signatera as a companion diagnostic to identify patients most likely to benefit and those who may be able to avoid adjuvant treatment. In the Phase 3 IMvigor011 trial, 250 ctDNA-positive MIBC patients without radiographic disease were randomized to Tecentriq versus placebo. Disease-free survival nearly doubled with Tecentriq (9.9 months vs 4.8 months). Median overall survival also improved (32.8 vs 21.1 months), and the 2-year survival rate favored Tecentriq (62.8% vs 46.9%). The agency framed the decision as the first approval for a ctDNA MRD-guided cancer therapy in the U.S., marking a regulatory milestone for circulating tumor DNA as a treatment-selection tool. For clinicians, the pairing of an immunotherapy with an MRD test shifts post-cystectomy decision-making away from imaging and staging alone toward molecular residual disease status.