A Phase III randomised trial of perioperative chemotherapy versus surveillance in upper tract urothelial cancer

INTERVENTION: Chemotherapy, Gemcitabine 1000mg/m2 day 1 and day 8 as 30 minute intravenous infusion in 500ml sodium chloride; and Cisplatin 70mg/m2 day 1 as a 4 hour intravenous infusion or (for participants with a creatinine clearance of 25‐49ml only) Carboplatin AUC 4.5 or AUC 5 (according to local practice) Carboplatin will be given to patients who are fit for chemotherapy and fulfil all trial entry criteria but have GFR 30‐49 ml/min. Surveillance, Patients allocated to surveillance will be seen at 4, 7, 10 and 13 weeks post randomisation ‐ equivalent to the end of cycle in patients receiving chemotherapy. Patients on surveillance will then be followed up for signs of recurrence at the same intervals as those who received chemotherapy.; Follow Up Length: 60 month(s) CONDITION: Topic: National Cancer Research Network; Subtopic: Bladder Cancer, Renal Cancer; Disease: Urothelium ; Cancer ; Malignant neoplasm of bladder PRIMARY OUTCOME: Disease free survival; Timepoint(s): The main time point of interest is three years after randomisation. SECONDARY OUTCOME: 1. Acute toxicity; Timepoint(s): Whilst patients are on treatment and up to 3 months post‐randomisation; 2. Contralateral second primary utTCC; Timepoint(s): The primary timepoint of interest is 3 years; 3. Invasive recurrence/second primary in the bladder; Timepoint(s): The primary timepoint of interest is 3 years after randomisation; 4. Late toxicity; Timepoint(s): 6 months, 2 years; 5. Metastasis free survival; Timepoint(s): The primary timepoint of interest is 3 years.; 6. Overall survival; Timepoint(s): The primary timepoint of interest is 3 years after randomisation; 7. Quality of life (QoL) as measured by the EORTC QLQ‐C30 and EQ5D modules.; Timepoint(s): We are collecting information on QoL up to 2 years post randomisation; 8. Treatment compliance (in the chemotherapy arm); Timepoint(s): Once chemotherapy has been completed; Trial feasibility; Timepoint(s): Defined by recruitment over the first two years INCLUSION CRITERIA: 1. Written informed consent 2. >or =18 years of age 3. Post radical nephro‐ureterectomy for upper tract tumour with predominant TCC component ‐ squamoid differentiation or mixed TCC/ small cell carcinoma (SCC) is permitted 4. Histologically confirmed TCC staged pT2‐pT4 pN0‐3 M0 or pTany N1‐3 M0 (providing all grossly abnormal nodes are resected). Patients with microscopically positive margins on pathology may be entered (providing all grossly abnormal disease was resected) 5. Satisfactory haematological profile (ANC> 1.5 x 109/L, platelet count 100 x 10/L) and liver function tests (bilirubin < 1.5 x ULN, AST and Alkaline phosphatase < 2.5 x ULN), Glomerular filtration rate = 30 mls/min 6. Fit and willing to receive adjuvant chemotherapy with first cycle to be commenced within 90 days of radical nephro‐ureterectomy if allocated 7. WHO performance status 0‐1. 8. Available for long‐term follow‐up; Target Gender: Male & Female ; Lower Age Limit 18 n