The CISTO Bladder Cancer Study will enroll patients whose bladder cancer has returned despite standard treatments and who are choosing between having their bladders removed and receiving more medicine into the bladder. Deciding on which treatment to choose after bladder cancer has returned is a challenging problem for patients and clinicians and was rated as the most important research question by the Bladder Cancer Advocacy Network Patient Survey Network. The CISTO Study will compare the impact of the treatment options of bladder removal and additional medicine into the bladder on patients’ quality of life and on the clinical outcomes that patients have rated as being most important. In order to represent the results of all patients confronting this challenging clinical situation, the research question will be evaluated on a large scale in real world practice settings. The CISTO study will recruit 900 patients and 25 caregivers at 28 sites across the US.