Multi-modal treatment for metastatic renal cancer: the role of surgery

Surgical intervention in the patients with metastatic renal cancer can occur in two settings: (1) to render a patient clinically free of all sites of primary disease and metastases, termed nephrectomy/metastasectomy, or (2) to resect the primary tumor in the face of unresectable metastatic disease prior to the initiation of systemic therapy, termed cytoreductive nephrectomy. Carefully selected patients with good performance status undergoing nephrectomy and subsequent metastasectomy may experience prolonged survival in the range of 30 months, which could be attributed to a combination of patient selection factors and the surgical resections. Randomized clinical trials from the United States and Europe have demonstrated a small but significant survival benefit to cytoreductive nephrectomy and cytokine therapy versus cytokine therapy alone which is measured in the range of 3-6 months and associated with overall survival of approximately 12 months. The precise mechanism by which cytoreductive nephrectomy improves survival is not known but may relate to reduction in the large primary immunosuppressive burden. Patient selection factors including performance status and serum factors (Hgb, corrected Ca++, LDH) stratify metastatic patients into risk groups, which are strongly associated with survival time in both medically and surgically treated patients with metastatic renal cancer. The development of multi-kinase and mTOR inhibitors has markedly improved survival in treatment naïve and previously treated patients with metastatic renal cancer , and these agents are currently under active clinical investigation in the neo-adjuvant and adjuvant setting.