A substantial proportion of patients with muscle invasive bladder cancer do not receive curative intent therapy, especially if unfit for or refuse radical cystectomy. Concurrent chemoradiation is an effective alternative to radical cystectomy, however systemic radio-sensitizing chemotherapy may have off target side effects. A Phase I study is accruing which will investigate the concurrent administration of a bladder cancer targeted antibody drug conjugate (Sacituzumab Govitecan) with radiotherapy. This trial in progress is a Phase I study of Adaptive RADiation therapy with concurrent Sacituzumab Govitecan (SG) for bladder preservation in patients with muscle invasive bladder cancer (MIBC). Eligible patients will have localized muscle invasive bladder cancer (MIBC) confined to the bladder. The initial cohort is expected to accrue 20 patients. The primary endpoint is to establish the safety, tolerability, and feasibility of bladder preservation therapy treatment with concurrent SG and adaptive image-guided radiation therapy for patients with localized MIBC. The secondary endpoints are to determine the bladder intact event-free survival (BI-EFS) with concurrent SG and radiation therapy for MIBC and compare to historical controls with other concurrent chemoradiation regimens. BI-EFS is defined as the time from treatment to the first documented occurrence of residual/recurrent MIBC, nodal or distant metastases on imaging, radical cystectomy, or death from any cause. Sacituzumab Govitecan targets TROP-2, a surface protein expressed in urothelial cancers of the bladder. SG will be delivered IV, 10 mg/kg, 21-day cycles for 1 loading cycle prior to radiation and two subsequent cycles with concurrent adaptive radiotherapy over a period of 6 weeks (64 Gy). Correlative objectives (Supported by NCI/NIH U54) and will involve 1) elucidation of the genetic and microenvironmental mechanisms that drive efficacy and resistance to combined ADC plus radiation therapy and 2) characterization of tumor clonal dynamics, immune repertoire editing, and imaging changes following treatment with SG plus radiation. To be determined. To be determined.