Treatment strategies for advanced renal cell carcinoma: A new paradigm for surgical treatment

The induction of targeted drugs for the treatment of metastatic renal cell carcinoma has changed the treatment strategy for systemic therapy. Surgical treatment for metastatic renal cell carcinoma should also be reconsidered in the light of the effect of targeted drugs. The clinical benefit of cytoreductive nephrectomy for cases of metastatic renal cell carcinoma was proved in randomized trials in the cytokine era. However, at present, there has not been level 1 evidence for this in the targeted therapy era. Patients with better performance status and without poor risk factors tend to benefit from cytoreductive nephrectomy. Two ongoing large-scale randomized studies might shed light on this issue. One of the remarkable differences in the efficacy between cytokines and targeted drugs, particularly tyrosine kinase inhibitors, is the reduction in the size of the primary tumors by tyrosine kinase inhibitors, including sunitinib and axitinib. Initial experiences with targeted therapy suggest that the neoadjuvant setting of tyrosine kinase inhibitors could be a viable option when the primary tumor shows local invasion and/or is unresectable. The present study does not support the routine neoadjuvant use of sunitinib because of the possibility of disease progression during the neoadjuvant therapy, and modest response and benefit. Axitinib, in contrast, shows larger reduction in the size of the primary tumor and might be used in the near future. Another issue is the combination of targeted therapy with metastasectomy. There is a lack of evidence for improved prognosis resulting from the neoadjuvant setting of tyrosine kinase inhibitors followed by metastasectomy. Further studies are warranted to investigate this.