
    low enrolment
  
['clear-cell metastatic renal cell carcinoma']
['sunitinib or pazopanib']

        Inclusion Criteria:

          -  Written informed consent

          -  ECOG Performance Status 0-1

          -  Favorable or intermediate MSKCC or Heng risk score

          -  Biopsy (primary tumour or metastases) confirming the diagnosis of predominantly clear
             cell RCC

          -  Resectable asymptomatic in situ primary (asymptomatic primary is defined as the
             absence of symptoms which can be exclusively assigned to the primary tumor such as
             flank pain and/or gross hematuria necessitating blood transfusion.)

          -  Tumour suitable to nephrectomy in the opinion of the urologist. Patients with Inferior
             vena cava thrombosis can be included

          -  Documented metastatic disease (CT scan or MRI)

          -  Life expectancy > or = 24 weeks

          -  Up to three different metastatic sites

          -  ≥ 3 metastatic lesions

          -  Platelets > 100,000/ml

          -  Haemoglobin > 9.0 g/dl

          -  neutrophils >1,500/mm3

          -  Bilirubin < or = 2 mg/dl, except for patients affected by Gilbert's syndrome

          -  AST and ALT < or = 2.5 times the UNL

          -  Serum albumin > the LNL

          -  Patients of childbearing age should use contraceptive methods during the study

        Exclusion Criteria:

          -  Prior surgery or systemic treatment for mRCC

          -  Bilateral RCC

          -  Brain and liver metastases

          -  Non-clear-cell histology

          -  Poor prognosis as defined by MSKCC or Heng criteria

          -  Documented widespread disease (> or =4 metastatic organ sites)

          -  Oligometastatic disease suitable of metastasectomy (<3 lesions confined at one organ
             site)

          -  Symptomatic primary tumour at presentation

          -  High surgical risk in the opinion of the urologist

          -  Patients with > 3 of the following surgical risk factors are not eligible:

               -  Serum albumin CTCAE v 4.0 grade 2 or worse

               -  Serum LDH > 1.5 times upper limit of normal

               -  Symptoms at presentation due to metastases

               -  Clinical stage T4 disease

               -  History of malabsorption syndrome

          -  Pregnant or breastfeeding women

          -  Concomitant cardiac disorders: cardiac failure NYHA> 2; Acute coronary syndrome or
             myocardial infarction or severe or unstable angina within the last 6 months as well as
             uncontrolled hypertension (sistolic>160, diastolic>90), arrhytmia requiring treatment
             (except for beta blockers or digossin)

          -  Uncontrolled diabetes

          -  Deep phlebitis not treated with LMWH or arterial thrombosis within the last 6 months

          -  HIV infection

          -  Active infections (> Grade 2 NCI-CTC v.3.0)

          -  Other cancer within the previous 5 years (except for in situ skin carcinoma,
             superficial bladder Ta, Tis, T1 and carcinoma of the cervix or every cancer with
             curative treatment within 5 years)
      