Novel agents for renal cell carcinoma require novel selection paradigms to optimise first-line therapy.

First-line therapies available for metastatic renal cell carcinoma (RCC) have increased rapidly with the recent introduction of three novel agents: sunitinib, temsirolimus and bevacizumab (in combination with interferon [IFN]). This expansion means that the selection of the optimal therapy for individual patients has become more difficult and increasingly important. A treatment algorithm based on tumour histology and patient risk status is currently used to guide clinical practice, but does not always allow specific treatment for individual patients to be identified. This is particularly true for the largest group of patients, who have favourable or intermediate risk clear cell RCC. Considerations guiding treatment selection for these patients include: potential for cure; and optimal progression-free survival (PFS) with good tolerability and quality of life. In patients who have a realistic opportunity for cure, bevacizumab combined with IFN might be the treatment of choice. However, sunitinib and bevacizumab combined with IFN produce similar PFS. Thus, if optimal PFS is the treatment goal, other factors must be considered. These include patient-related factors such as the needs, circumstances and comorbidities of individual patients and the associated side effects of bevacizumab combined with IFN and sunitinib. More data are currently available to support treatment decisions based on the latter and these are considered in detail, highlighting factors that may lead to selection of bevacizumab combined with IFN or sunitinib in individual patients.