Multimodal approaches in the management of locally advanced and metastatic renal cell carcinoma: combining surgery and systemic therapies to improve patient outcome.

Patients with locally advanced renal cell carcinoma are at high risk of metastatic relapse following surgery. Patients with metastatic disease have a poor prognosis and few systemic therapy options. Radiation, chemotherapy, hormonal therapy, vaccines, and immunotherapy have all been tested as adjuvant therapy without benefit. Neoadjuvant therapy in the metastatic setting holds promise as a new treatment paradigm. It can serve as a litmus test to allow proper patient selection for aggressive surgical intervention and may provide limited downstaging of primary tumors in selected cases. It can also provide a histologic assessment of the effect of targeted therapy. Application of this paradigm may have merit in the locally advanced setting as well. Effective adjuvant therapy for renal cell carcinoma remains elusive. The benefit of new targeted therapies has yet to be tested in this setting. Neoadjuvant strategies that integrate aggressive surgical intervention with systemic therapy may hold promise as a treatment paradigm.