Checkpoint Inhibition and Chemoradiotherapy as Bladder Sparing Treatment in UC

Inclusion Criteria: 1. Willing and able to provide informed consent 2. Age ≥ 18 years 3. Patients with cT2-4aN0-2M0 urothelial bladder cancer, who are amendable for chemoradiation and who are seeking an alternative to radical cystectomy and/or patients who are medically unfit for surgery. 4. Lymph nodes should be amenable for inclusion into the radiation field. 5. World Health Organization (WHO) performance Status 0 or 1. 6. Urothelial cancer is the dominant histology (\>70%). A small cell component is not allowed. 7. Formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks from diagnostic TUR available. 8. Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥1.0x109/L, Platelets ≥100 x109/L, Hemoglobin ≥5.5 mmol/L, GFR\>30 ml/min as per Cockcroft-Gault formula, AST ≤ 2.5 x ULN, ALT ≤2.5 x ULN, Bilirubin ≤1.5 X ULN 9. Negative pregnancy test (βHCG in urine or blood) for female patients of childbearing potential within 2 weeks prior to day 1 of start immunotherapy. 10. Highly effective contraception for both male and female subjects if the risk of conception exists. Female patients of childbearing potential must comply with contraception methods as requested by the study protocol. Exclusion Criteria: 1. Previous pelvic irradiation 2. Upper tract urothelial cancer 3. Extensive carcinoma in situ (CIS) of the bladder 4. Bilateral hydronephrosis 5. Previous intravenous chemotherapy for bladder cancer 6. Contra-indication to one of the study treatment components, or mpMRI 7. Subjects with active autoimmune disease in the past 2 years. Patients with diabetes mellitus, properly controlled hypothyroidism or hyperthyroidism, vitiligo, psoriasis or other mild skin disease can still be included. 8. Documented history of severe autoimmune disease (e.g. inflammatory bowel disease, myasthenia gravis). 9. Prior CTLA-4 or PD-(L)1 -targeting immunotherapy. 10. Known history of Human Immunodeficiency Virus, active tuberculosis, or other active infection requiring therapy at the time of inclusion. 11. Positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA) 12. Underlying medical conditions that, in the investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of adverse events 13. Medical condition requiring the use of immunosuppressive medications, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) will be allowed. 14. Use of other investigational drugs four weeks before study drug administration 15. Malignancy, other than urothelial cancer, in the previous 2 years, with a high chance of recurrence (estimated \>10%). Patients with low risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible. 16. Pregnant and lactating female patients. 17. Major pelvic surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis. 18. Severe infections within 2 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.