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Cytoreductive Nephrectomy in Metastatic Clear-Cell Renal Cell Carcinoma: Perspectives in the Tyrosine Kinase Inhibitor Era

^aDepartment of Oncology, Oncology Centre, Addenbrooke's Hospital, Cambridge, United Kingdom; ^bDepartment of Surgical Oncology and ^cDepartment of Oncology, University of Cambridge & Addenbrooke's Hospital, Cambridge, United Kingdom

Key Words. Cytoreductive surgery • Clear-cell renal cell cancer • Immunotherapy • Tyrosine kinase inhibitors

Correspondence: Correspondence: Tim Eisen, Ph.D., F.R.C.P., Department of Oncology, Box 193, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom. Telephone: +44(0)1223-769312; Fax: +44(0)1223-769313; e-mail: tim.eisen{at}medschl.cam.ac.uk

Received May 22, 2008; accepted for publication December 15, 2008.

Disclosure: Employment/leadership position: None; Intellectual property rights/inventor/patent holder: None; Consultant/advisory role: Tim Eisen, Bayer, Wyeth, Pfizer, Roche, Novartis; Honoraria: Tim Eisen, Bayer, Wyeth, Pfizer, Roche; Research funding/contracted research: Tim Eisen, Bayer, Pfizer; Ownership interest: Tim Eisen, Astra Zeneca; Expert testimony: None; Other: None. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers.

Cytoreductive nephrectomy in combination with adjuvant immunotherapy is an established treatment option for selected patients with metastatic clear-cell renal cell carcinoma (mCC-RCC). Multitargeted antiangiogenic and mammalian target of rapamycin tyrosine kinase inhibitors (TKIs) are now established treatment paradigms in patients with mCC-RCC. Given that all the recent seminal TKI trials in mCC-RCC provide no evidence base for the use of cytoreductive nephrectomy in the TKI era, it is not presently clear where such a surgical approach fits into the treatment paradigm.

This review summarizes the evidence for the management of mCC-RCC and outlines novel approaches to be tested within future trials if the initial proposed phase III trials in this setting, using sunitinib, are successful. Overall, two principal questions need addressing. First, is cytoreductive nephrectomy necessary in the TKI era? Second, if so, what is the most appropriate scheduling of TKI therapy with cytoreductive nephrectomy?