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Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma: Is It Still Imperative in the Era of Targeted Therapy?

Authors' Affiliation: Departments of Urology and Medicine, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California

Requests for reprints: Allan J. Pantuck, Department of Urology, David Geffen School of Medicine at University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1738; E-mail: apantuck{at}mednet.ucla.edu, or Arie S. Belldegrun, Division of Urologic Oncology, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA 90095, or Robert A. Figlin, Departments of Medicine and Urology, David Geffen School of Medicine at University of California at Los Angeles, 2333 Peter Ueberroth Building, Los Angeles, CA 90095.

In the era before cytokine therapy, controversy existed about the need for cytoreductive nephrectomy in treating patients with metastatic renal cell carcinoma. In 1978, Dekernion showed that nephrectomy alone had no effect on survival. During this period, removal of the malignant kidney was confined to palliative therapy in some settings of metastatic RCC, such as pain related to the kidney mass, intractable hematuria, erythrocytosis, uncontrolled hypertension, or poorly controlled hypercalcemia. When interleukin-2 was approved by the Food and Drug Administration in 1992, the role of nephrectomy was reexamined. After a decade of controversy, two randomized controlled studies established that cytoreductive surgery has a role in properly selected patients and offers a survival advantage when done before cytokine therapy. Unfortunately, the mechanisms underlying this benefit remain poorly understood. Immunotherapy may work best when there is a small volume of cancer present, and removing a large primary tumor may prevent the seeding of additional metastases. Data have also suggested that primary tumors were capable of producing immunosuppressive compounds that might decrease the efficacy of immunotherapy. Another hypothesis suggested that removing the kidney altered the acid/base status of the patient to such an extent that the growth of the tumor was hindered. With the emergence in 2006 of two targeted agents for advanced renal cell carcinoma, the role of cytoreductive nephrectomy has reemerged as a source of controversy. Although evidence-based medical practice suggests a role for nephrectomy before the use of targeted agents, the arguments for and against this practice will be weighed.