Unified approaches to surgery and systemic therapy for renal cell carcinoma

RCC remains the most lethal of genitourinary malignancies. It will be essential to rationally integrate surgery and systemic therapy to improve outcomes in RCC. Despite substantial efforts to date, there is no current role for adjuvant therapy following nephrectomy for clinically localized disease. There are several studies in progress that aim to identify effective agents in the adjuvant setting, including mTOR and tyrosine kinase inhibitors as well as a monoclonal antibody against CA IX. For locally advanced disease, it has been proposed that neoadjuvant therapy may make unresectable disease resectable, enable partial nephrectomy, or shrink venous tumor thrombus. These theoretical goals remain in need of further study. For patients with metastatic RCC, the correct paradigm remains to be elucidated for integrating cytoreductive surgery and systemic therapy. In particular, the proper criteria for selecting patients for surgery, the benefit of cytoreduction in the targeted therapy era, and the correct order of surgery and systemic therapy are all active areas of debate and research.