Feasibility of Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma

Inclusion Criteria: * Written informed consent * Age \> 18 years * Histological and radiological defined UTUC: Histologically-confirmed diagnosis of predominantly urothelial carcinoma of the upper urinary tract Patients with UTUC cT2-pT4 cN0-N1 M0 (TNM classification) * Women with negative serum pregnancy test within 14 days of first dose of study treatment and agreement to use effective contraception * Patients without bladder cancer or with concomitant non muscle invasive bladder cancer * Adequate organ system function defined as follows: Hematologic: Absolute neutrophil count (ANC) 1.5 X 109/L; Haemoglobin 5.6 mmol/L (9.02g/dL); Platelets 100 X 109/L; Prothrombin time (PT) or international normalized ratio (INR)b 1.2 X ULN; Activated partial thromboplastin time (aPTT)1.2 X Upper limit of normal (ULN). Hepatic: Total bilirubin 1.5 X ULN; Alanine amino transferase (ALT) and Aspartate aminotransferase (AST) 2.5 X ULN. Renal: GRF \<or\> 55 ml/min: Electrolytes: potassium and calcium: within normal limits. * CT scan of the chest, abdomen and pelvis and Bone scan without evidence of distant metastasis Exclusion Criteria: * Histology of pure adenocarcinoma, pure squamous cell carcinoma, sarcomatoid or predominant small cell carcinoma. * History of cardiovascular conditions within the past 6 months. * Incidentally found asymptomatic pulmonary embolism (PE) or recent deep vein thrombosis (DVT) is not an exclusion criteria but requires anticoagulation treatment. * Any major contraindication to a surgical procedure. * Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures. * Active infection contraindicating chemotherapy * Other active neoplasms. Patients with in situ cervical carcinoma, non-melanoma skin cancer or prostate cancer T1 Gleason \<7, Prostate specific antigen (PSA) \<10. Patients with past medical history of cancer can be included if diagnosed at least 4 years ago. * Concomitant muscle invasive bladder cancer * Patients who have been or still are on methotrexate treatment.