EORTC-GU group expert opinion on metastatic renal cell cancer

There is no consensus on the detailed surveillance of renal cell cancer (RCC) patients after radical resection of the kidney. Where relapse is unlikely, one reasonable option would be to confine investigations to chest X-ray and abdominal ultrasound – carried out at 3-month intervals during the first year, but less frequently thereafter. These investigations could be supplemented by annual computerised tomography (CT) of the chest and abdomen. Where risk is intermediate or high, more frequent CT should be undertaken, taking into account the risks of repeated radiation exposure. Since the emergence of new and more effective treatments for metastatic disease, follow-up has tended to become more challenging not only with respect to disease assessment but also for evaluation of toxicity [Level 5].The diagnostic work-up in metastatic RCC should include a history, physical examination and comprehensive blood screen. In addition, patients to be treated with targeted agents should have a thyroid function test. In patients with a relevant clinical history or who are otherwise at risk, cardiac function should be assessed, and this is also advisable in asymptomatic patients [Level 2b].Nephrectomy is an important component of the multimodality treatment of mRCC. This procedure induces spontaneous regression of metastases in a small number of patients [Level 4]. More generally, it improves the survival of patients who subsequently receive immunotherapy [Level 1]. However, it is not yet known whether this benefit is also seen in patients treated with targeted agents [Level 2b].Certain patients with metastases (even at multiple sites) have lesions that are resectable. Surgery is potentially curative in these cases and can be undertaken prior to use of cytokines or targeted agents [Level 2b].Vaccine-based therapies may have potential, particularly when disease burden is low [Level 4]. The outcome of ongoing trials is awaited.Metastatic RCC responds, albeit at a low rate, to cytokines. These agents may be helpful for a subgroup of patients. However, for the great majority, and certainly for those with intermediate- or poor-risk disease, cytokines confer no benefit [Level 1b].Choice of initial medical management in patients with metastatic clear-cell RCC should be guided by the pivotal, randomised studies. On the evidence available, the first-line therapy in patients with good- or intermediate-risk mRCC should be either sunitinib [Level 1b] or bevacizumab plus interferon [Level 1a]. In patients ineligible for sunitinib or bevacizumab plus interferon, sorafenib is an option, as is high-dose interleukin 2 if performance status is sufficiently good [Level 2b]. In patients with poor prognosis (as defined in the pivotal trial), temsirolimus is recommended [Level 1b]. In this group, sunitinib could be an alternative [Level 2b]. The role of targeted agents in the treatment of patients with RCC of non-clear-cell histologies remains to be established. In cytokine refractory patients, sorafenib is recommended [Level 1b]. Everolimus is the agent of choice when patients have progressed on a tyrosine kinase inhibitor [Level 1b].