Muscle-Invasive Bladder Cancer: A Watershed Moment

The treatment of muscle-invasive bladder cancer (MIBC) has evolved substantially over the past several decades. Muscle-invasive bladder cancer is a disease of older individuals who often have comorbidities and age-associated changes in physiologic function. This has historically created a disconnect between the efficacy of treatment for MIBC as defined in the setting of clinical trials and the effectiveness of treatments when applied to the broader population of patients. 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. The next decade will witness an unprecedented convergence of powerful therapeutics, precise biomarkers, and risk-adapted strategies creating a watershed moment to redefine MIBC care.