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

Abstract

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.

Renal cell carcinoma metastatic to the stomach: single‐centre experience and literature review

“…sorafenib and sunitinib, for metastatic RCC, marking a new era in the management of the disease, has further complicated the situation. Thus, there currently appears to be no valid basis to assess the possible benefit of cytoreductive surgery, directed against metastatic tumour sites or even against the primary tumour itself, if patients with disseminated disease are treated with these new anticancer agents [29,30].…”

Potent Anticarcinoma Activity of the Humanized Anti-CD70 Antibody h1F6 Conjugated to the Tubulin Inhibitor Auristatin via an Uncleavable Linker

“…4B). Distant metastases are common in RCC and nearly one fourth of the patients display metastases at presentation whereas another 50% develop metastases during the follow-up (26,27). To assess the therapeutic effects of h1F6 antibody-drug conjugates on tumor dissemination, we developed a model of experimental RCC metastasis.…”

Complication and Outcomes Associated With Surgical Management of Renal Cell Carcinoma: Literature Review.

“…In the setting of metastatic RCC, level I evidence supports the benefits of cytoreductive nephrectomy prior to prepared immunotherapy (36,37) . Although the new era of targeted therapy has demonstrated responses in the primary tumor, cytoreductive nephrectomy typically remains an integral part of therapy (38,39) . Whereas cytoreductive surgery still has a major function in the treatment of metastatic RCC, for patients with sRCC, numerous question the survival benefit of cytoreductive surgical treatment (28,29) .…”