Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer

Inclusion Criteria: 1. Be willing and able to provide written informed consent for the trial. 2. Be 18 years of age on day of signing informed consent. 3. Have histologically-confirmed diagnosis of muscle-invasive T2-T4a, Nx or N0 urothelial cell carcinoma of the bladder. Subjects with tumors of mixed transitional/non-transitional cell histology are allowed, but transitional cell carcinoma must be the predominant histology (\>50%). Subjects with predominant or exclusively non-transitional cell histology are not allowed. 4. Must have undergone maximal transurethral resection of the bladder tumour, as is judged as safe as possible by the urologist performing the resection, within 42 days of treatment. Where patient has only had a biopsy/partial resection and is otherwise eligible for entry into the study, the case should be rediscussed with the referring urologist to see whether further resection would be feasible prior to embarking with the chemo-radiotherapy. 5. Have elected not to undergo radical cystectomy, or are unsuitable for radical cystectomy. 6. Planned for chemoradiotherapy as definitive treatment. 7. Have a performance status of 0 or 1 on the ECOG Performance Scale 8. Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of registering the patient on the trial. * Absolute neutrophil count (ANC): ≥1.5 X 10\^9/L * Platelets: ≥100 X 10\^9/L * Hemoglobin: ≥9 g/dL without transfusion or EPO dependency * Calculated creatinine clearance ≥50 mL/min * Serum total bilirubin: ≤ 1.5 X ULN OR * Direct bilirubin ≤ ULN for participants with total bilirubin levels: \> 1.5 ULN * AST and ALT: ≤ 2.5 X ULN * Albumin: \>25 g/dL * International Normalized Ration (INR) or Prothrombin Time (PT): ≤1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants) * Activated Partial Thromboplastin Time (aPTT): ≤1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants) 9. Female participant of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to registering the patient. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 10. Female participants of childbearing potential should be willing to use two methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. 11. Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 12. Willing to consent to the use of their collected tumour specimen, blood and urine as detailed in the protocol for future scientific research including but not limited to DNA, RNA and protein based biomarker detection. Exclusion Criteria: 1. Has concurrent extra-vesical (i.e. urethra, ureter or renal pelvis) urothelial cell carcinoma of the urothelium. Patients who have involvement of the prostatic urethra with urothelial cell cancer (TCC) that was visibly completely resected and no evidence of stromal invasion of the prostate remain eligible. 2. Evidence of tumour-related moderate/severe hydronephrosis unless stented or with nephrostomy to preserve renal function. 3. Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy. 4. Bulky T3/T4a tumours unsuitable for curative treatment (i.e. \>10 cms in any dimension); node positive disease 5. Evidence of distant metastatic disease on CT chest/abdomen/pelvis performed within 42 days prior to study entry. Patients with pelvic lymph nodes deemed to be 'positive' are not eligible for the study unless histological confirmation of the largest most suspicious node is negative for malignancy. Patients with known CNS metastatic disease are excluded from the study 6. Prior pelvic radiotherapy 7. Has had prior intravenous chemotherapy, targeted small molecule therapy, or radiation therapy for treatment of bladder cancer. Prior intravesical use of BCG and mitomycin is permissible. 8. Unsuitable for concurrent cisplatin based chemoradiotherapy based on: * CTCAE v.4.03, Grade \>2 audiometric hearing loss (25dB in two consecutive wave ranges) if previously performed. * CTCAE v.4.03, Grade \>2 peripheral neuropathy 9. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of treatment. 10. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to registering the patient. Patients with adrenal insufficiency receiving replacement dose steroids are allowed on the trial. 11. Has a known history of active TB (Bacillus Tuberculosis) 12. Hypersensitivity to pembrolizumab or any of its excipients. 13. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 14. Prior or concurrent known additional malignancy of any site unless disease free for 5 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, Stage T1a well differentiated prostatic carcinoma in men (Gleason = 3+3, PSA \<5) 15. Has any history of active autoimmune disease, Stevens-Johnson syndrome or Guillain-Barre. Exceptions to this are: * Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone. * Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen who are also be eligible for this study. 16. Has known history of, or any evidence of active, non-infectious pneumonitis. 17. Has an active infection requiring systemic therapy. 18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. 19. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 20. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. 21. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 22. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 23. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). 24. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.