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Radical cystectomy with perioperative systemic therapy, and radiation with concurrent chemotherapy, represent standards of care for MIBC. Immune checkpoint blockade (ICB) has now been integrated into the neoadjuvant and adjuvant settings. The clinical utility of circulating tumor DNA, as a measure of minimal residual disease, to inform the integration of adjuvant ICB is now being explored in several clinical trials. Antibody-drug conjugates in combination with ICB administered in the perioperative setting are poised to further improve outcomes. More effective systemic therapy regimens, yielding higher pathologic complete response rates relative to historical regimens, have raised the possibility of risk-adapted individualized bladder-sparing treatment strategies. 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