The timing of immunotherapy and nephrectomy in multimodality treatment of metastatic renal cell carcinoma

Multimodality treatment of metastatic renal cell carcinoma with immunotherapy and cytoreductive surgery is controversial. Especially the benefit of removing asymptomatic primary tumors in synchronous metastatic renal cell cancer has been debated since several nonrandomized, retrospective studies revealed an improved response to immunotherapy and prolonged survival following initial nephrectomy. Two recent randomized prospective trials both demonstrated a prolonged survival in those who were randomly assigned to undergo nephrectomy of the primary tumor prior to treatment with interferon alfa-2b than in those who were assigned to undergo treatment with interferon alfa-2b alone. In these trials the survival benefit was limited and strongly influenced by overall performance score. The timing of immunotherapy, either as neoadjuvant (prior to nephrectomy) or adjuvant treatment (following nephrectomy) in the multimodality approach of synchronous metastatic renal cell carcinoma remains controversial. Selection of patients, the possible mechanisms underlying the survival advantage of the combination of nephrectomy and immunotherapy, and the timing of the treatment modalities are discussed herein.