Consolidative Therapy After EV + Pembrolizumab in Muscle Invasive Bladder Cancer, REINFORCE Trial

OUTLINE: This is a single arm, phase I/II study of consolidative therapy after initial favorable response after enfortumab vedotin and pembrolizumab. For patients with a complete response (cCR) in the bladder, local consolidative therapy (radiation or cystectomy) as described below is encouraged but not required. They will participate in a discussion with the treating physician regarding the limitations of a cCR. For patients with residual tumor in the bladder (not achieving a cCR), local consolidative therapy, either in the form of radiation or cystectomy will be delivered, per shared decision-making with their treating physician. Concurrent radiosensitizing chemotherapy will be delivered with radiation therapy to the bladder, whenever feasible. Regardless of the disease status in the bladder, patients with residual disease outside the bladder receive metastasis-directed therapy (MDT), as described below. RADIATION TO THE BLADDER/PELVIS: Patients undergo radiation therapy to the bladder with intensive-modulated radiation therapy (IMRT)/volume modulated arc therapy (VMAT) daily for a total of 20 fractions over 4 weeks. Patients may undergo pelvic lymph node-directed radiation therapy with simultaneous integrated boost to the bladder daily for 20 fractions, if indicated. Patients also receive radiosensitizing chemotherapy, per physician discretion and according to standard of care, concurrently with radiation therapy. CYSTECTOMY: Patients undergo radical cystectomy with pelvic lymph node dissection on study. MDT: Patients undergo metastasis-directed radiation therapy with stereotactic body radiation therapy (SBRT) for 3-5 fractions, as determined by the treating physician. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET)/CT and collection of blood and urine samples throughout the trial, undergo re-transurethral resection of bladder tumor (re-TURBT) on study, and undergo cystoscopy during follow-up. After completion of study treatment, patients are followed up every 3 months for up to 12 months (1 year) on study.