Bladder cancer showdown: can radiation and chemotherapy match surgery?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Patients ≥ 18 years of age. 2. Pure or predominant urothelial carcinoma (including other histologic subtypes, with the exception of small cell carcinoma, as a minority component). 3. Performance status of 0 to 1, according to the Eastern Cooperative Oncology Group (ECOG) criteria. 4. Life expectancy of ≥ 3 months. 5. Histologically confirmed T2, T3, or T4a stage bladder cancer (pure or predominant urothelial carcinoma) cN0 or cN1 or cN2 (if lymph nodes within the surgical and radiation fields and size ≤ 2 cm). 6. Patients who are candidates for neoadjuvant cisplatin and have undergone TURBT (preferably maximal) prior to treatment. 7. Adequate bladder function (defined as the ability to store and void urine effectively, without symptoms of dysfunction or incontinence). 8. Neutrophil count ≥ 1500/mm³. 9. Platelet count ≥ 100,000/mm³. 10. Hemoglobin count \> 10 g/dL. 11. Glomerular filtration rate greater than 40 mL/min. 12. Serum bilirubin \< 1.5 times the upper limit of the normal reference range and SGOT and SGPT \< 1.5 times the upper limit of the normal reference range. 13. Absence of comorbidities that contraindicate treatment. 14. Capable of giving signed and dated informed consent prior to any mandatory study-specific procedures, sampling, and analyses, which includes compliance with the requirements and restrictions listed in the informed consent form and study protocol. 15. For inclusion in i) optional exploratory genetic research and ii) optional biomarker research, patients must meet the following criteria: * Provide informed consent for genetic research prior to sample collection. * Provide informed consent for biomarker research prior to sample collection. * If a patient declines to participate in optional biomarker research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study. Exclusion Criteria: 1. Presence of multiple primary tumors or multiple foci of carcinoma in situ (CIS) (including in the upper tract) that are not candidates for bladder preservation with radiochemotherapy (definition at the discretion of the investigator). 2. Age \> 80 years. 3. Pure adenocarcinoma or pure squamous carcinoma or pure small cell or large cell neuroendocrine carcinoma, micropapillary, sarcomatoid or nested. 4. Metastatic or unresectable disease. 5. Sensory neuropathy Grade ≥ 2. 6. Hearing impairment Grade ≥ 2. 7. Having a known additional malignancy that has progressed or required active treatment in the last 5 years, except superficial bladder cancer and/or carcinoma in situ, basal cell carcinoma of the skin or carcinoma in situ of the cervix. 8. Clinically significant cardiovascular disease - functional class III-IV according to the New York Heart Association (NYHA) Classification of heart failure. 9. Patients considered to be at high medical risk due to severe and uncontrolled disease, active or non-malignant systemic disease, and severe or potentially severe infection that may affect response to treatment or increase the risk of adverse events. 10. Immunocompromised patients. 11. Inflammatory bowel disease. 12. Patients with known active hepatitis (i.e., hepatitis B or C). 13. Patients receiving any prior systemic chemotherapy in the last 5 years for other tumors and at any time for muscle-invasive bladder cancer. 14. Patients who have received prior systemic immunotherapy at any time, either in the setting of non-muscle-invasive bladder cancer or in treatment for other types of cancer. 15. Prior pelvic radiotherapy. 16. Patients, male or female, who do not agree to use an effective method of contraception throughout treatment and until 6 months after discontinuation of treatment. 17. Women who are pregnant or currently breastfeeding. 18. The investigator's judgment that the patient should not participate in the study if the patient is unlikely to comply with the procedures, restrictions, and requirements. 19\. Prior Randomization to the present study.