Patients must be deemed unfit for radical cystectomy by the treating physician, or the patient must refuse radical cystectomy, which is considered standard of care for these patients; the reason for patients not to undergo cystectomy will be clearly documented Full recovery from cystectomy or nephroureterectomy within weeks following surgery Subjects with NMIBC must be suitable for and willing to undergo a radical cystectomy at the completion of study therapy Medically unfit to undergo cystectomy or electively choosing to forego cystectomy Patient is a candidate for radical cystectomy as a potentially curative option Patients with MIBC (predominantly urothelial carcinoma) with clinical stage T-Ta and N=< disease (solitary lymph node measuring < cm) and M and deemed eligible for radical cystectomy PRE-CHEMORADIATION SAMPLE COLLECTION: Patients with muscularis propria invasion clinical stages to (T-a, N or N+, M or T with N+), who are not candidates for radical cystectomy\r\n* Patients may have undergone partial cystectomy for removal of bladder tumor prior to chemoradiation; patients who have down-staged from M disease to M with prior platinum-based chemotherapy will be eligible\r\n* Staging is determined prior to chemoradiation STUDY TREATMENT: Patients with muscularis propria invasion clinical stages to (T-a, N or N+, M or T with N+), who are not candidates for radical cystectomy\r\n* Patients may have undergone partial cystectomy for removal of bladder tumor prior to chemoradiation; patients who have down-staged from M disease to M with prior platinum-based chemotherapy will be eligible\r\n* Staging is determined prior to chemoradiation Patients who desire and are candidates for radical cystectomy No prior cystectomy Prior cystectomy Be a medically appropriate candidate for radical cystectomy as determined by an attending urologist and be planning to receive cystectomy Ineligible for radical cystectomy or refusal of radical cystectomy Patients must have undergone cystectomy (total cystectomy, radical cystectomy +/- pelvic lymph node dissection) with no evidence of macroscopic residual disease Patients treated with simple cystectomy with macroscopically negative margins are eligible for this study Planned radical cystectomy with pelvic lymph node dissection Patient is ineligible, declines, or is considered ineligible to undergo radical cystectomy Prior cystectomy Indication for radical cystectomy for urothelial cancer Must have had radical surgical resection (e.g. radical cystectomy), performed within the last days Patients must be considered able to tolerate systemic chemotherapy combined with pelvic radiation therapy, and radical cystectomy Patients judged not to be candidates for radical cystectomy; patients with pN+ or Tb disease are considered to have unresectable disease Patients who are not currently candidates for radical cystectomy (e.g. patient refuses surgery, comorbidities preclude major surgery, etc.) Adjuvant platinum-based chemotherapy following radical cystectomy with recurrence > months from completion of therapy is permitted. Radical cystectomy has been declined by the patient in a signed special section of the informed consent, whereby there is a clear explanation by the investigator to the subject that a delay of cystectomy may increase his/her chance of disease progression, the results of which may lead to serious and life threatening consequences. The participating urologist judges that the standard next therapy, based on present urologic guidelines for this patient, is radical cystectomy Medically appropriate candidate for radical cystectomy, as per Memorial Sloan-Kettering (MSK) or participating site attending urologic oncologist Patients must be eligible for radical cystectomy and refuse this standard of care treatment or not be a surgical candidate for radical cystectomy based on other comorbidities Medically appropriate candidate for radical cystectomy, as per MSKCC or participating site attending urologic oncologist Patients must have a Zubrod performance status of , , or and in the registering physicians opinion be medically suitable to undergo cystectomy Participants must be a candidate for a trans-urethral resection of the bladder tumor (TURBT), cystectomy (partial or radical) or cystoscopy with biopsy at a participating organization Medically appropriate candidate for radical cystectomy as per MSKCC attending urologic oncologist PRE-REGISTRATION INCLUSION CRITERIA: Be a candidate for radical cystectomy Be a candidate for radical cystectomy Patients with recurrent T disease who do not wish to have cystectomy. Patient is either ineligible for or declines radical cystectomy; the investigator must explain that a delay in cystectomy may increase the patients chance of disease progression Patients whom, in the opinion of the treating urologic oncologist, should undergo cystectomy due to high-risk features Bladder cancer, undergoing radical cystectomy and ileal conduit diversion Undergoing elective open radical cystectomy Patients who undergo an open, elective radical cystectomy Anticipated radical cystectomy with ileal conduit or orthotopic neobladder Scheduled for elective radical cystectomy and urinary diversion for bladder cancer Patient unsuitable for or refusing radical cystectomy Patients who do not undergo radical cystectomy will be withdrawn from the study Planning to undergo radical cystectomy or chemotherapy-radiation for Urothelial Cell Carcinoma Patient is scheduled for radical cystectomy and lymph node dissection Patients who have had a cystectomy or prior diagnosis of muscle invasive disease (T\n or greater) Patients diagnosed with bladder cancer with planned cystectomy and urinary diversion, +/- neoadjuvant chemotherapy Deemed to not be a candidate for radical cystectomy by attending urologic oncologist or refuse radical cystectomy