Advanced renal cell carcinoma (RCC) is a disease that is highly resistant to systemic therapy and is difficult to treat. Nephrectomy should be seriously considered in patients who present with metastatic disease prior to systemic therapy, and surgery remains a reasonable option in patients who present with resectable metastases. Numerous studies with many different treatment modalities, including chemotherapy, immunotherapy, and radiation therapy, have failed to consistently benefit patients, with no single agent or combination therapy showing a reproducible response proportion of 20% or higher. Interleukin-2 (IL-2) and interferon-alfa (IFN alfa)-based therapies remain the most commonly used agents to treat patients with advanced disease, demonstrating low but reproducible response proportions in the 10% to 20% range, with durable responses of 5% or less. Recent randomized studies demonstrate a survival advantage for patients receiving systemic IFN-based therapy, but this advantage is marginal. Novel treatment strategies are being investigated, with some encouraging early results using vaccines and allogeneic bone marrow transplant. The identification of new agents with more effective antitumor activity is a high priority in the treatment of advanced RCC.
