Renal cell carcinoma is a potentially devastating cancer, and when metastatic, remains incurable with currently available systemic therapy. Surgical nephrectomy remains the only proven modality which can offer curative options for patients with resectable disease. Further, cytoreductive nephrectomy continues to play a role in the metastatic disease setting. The use of targeted therapy as an adjunct to surgical resection is beginning to be explored in both of these clinical scenarios. Immediate questions regarding preoperative treatment with VEGF pathway targeted therapy include issues surrounding the safety of these agents in use in the perioperative time period, the expectations for response in the primary tumor, the optimal duration of therapy, and the clinical settings in which this therapy may be most beneficial. This review will discuss the current experience with neoadjuvant or preoperative therapy in locally advanced or metastatic renal cell carcinoma and will overview the challenges and opportunities which lie ahead for this form of multimodality therapy.
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