Purpose of review IL-2 or IFN-alpha induce remissions and prolong life in patients carefully selected for a possibly toxic treatment. However, there is a need for better-tolerated and more effective therapies, especially in patients with co-morbidities and those resistant to systemic immunotherapy. Recent achievements in the treatment of advanced renal cell carcinoma highlight potentially significant improvements. Recent findings Cytoreductive surgery or radiation of metastases seems beneficial in well-selected patients, especially as immunotherapy is available. Immune cells within the tumour correlate with response and survival, indicating the importance of local immune modulation. Such modulation has allowed the introduction of well-tolerated treatments such as the inhalation of IL-2 to control lung metastases, which results in a significant survival benefit for high-risk patients, as suggested by a recent outcome study in 200 patients. Antibody-based tumour targeting against cG250, specifically expressed on renal cell carcinoma, seems to stabilize progressive metastatic disease and does not induce toxicity. Vaccination strategies are also well tolerated, but have not yet shown convincing results in advanced disease. Other approaches have not fulfilled expectations. Thalidomide has significant neurotoxicity and its efficacy was not confirmed in recent studies. Stem cell transplantation has significant toxicity, and cannot yet be recommended, but may have future potential. Summary Cytokine-based immunotherapy can now be considered standard in the treatment of metastatic renal cell carcinoma. There is good evidence that additional local procedures such as surgery, radiation or the inhalation of IL-2 improve response and survival in metastatic disease with moderate toxicity, resulting in a significant improvement for patients suitable for these approaches.
