INVITED REVIEW The role of surgery for metastatic renal cell carcinoma in the era of targeted therapies Pierre Bigot • Souhil Lebdai • Alain Ravaud • Abdel Rahme `ne Azzouzi • Jean-Marie Ferrie `re • Jean-Jacques Patard • Jean-Christophe Bernhard Received: 14 November 2012 / Accepted: 15 March 2013 Ó Springer-Verlag Berlin Heidelberg 2013 Abstract Purpose With the emergence of targeted therapies, the indications of cytoreductive nephrectomy have to be rede- fined. This review article presents the evidence data guiding our current indications of surgery in the management of metastatic renal cell carcinoma (mRCC) in the era of tar- geted therapies. Methods A nonsystematic review of the electronic dat- abases PubMed and MEDLINE from 1980 to 2012 was performed and limited to English language. Results Two studies based on immunotherapy (EORTC 30947 and SWOG 8949) were at the origins of the recom- mendations on initial nephrectomy for patients with mRCC. Since the introduction of angiogenesis inhibitors, there is still no high-level evidence from prospective studies assessing the indication of surgery for mRCC. However, surgery still has its importance in the management of pri- mary tumors and metastasis with the objective of an optimal balance between morbidity, quality of life, and survival. The treatment sequence between surgery and targeted therapies is still to be established and two randomized prospective studies were then specifically designed and are currently recruiting. Conclusions Preliminary evidence data from retrospec- tive series seem to be in favor of a benefit of surgery for patients with good and intermediate prognosis. However, patients’ inclusions in current prospective studies are highly recommended to clearly precise nephrectomy’s indications. Keywords Metastatic renal cell carcinoma Á Targeted therapy Á Surgery Á Primary tumor response Á Neoadjuvant therapy Á Renal cell carcinoma Á Tyrosine kinase inhibitor Á Vascular endothelial growth factor Introduction The management of metastatic renal cancer (mRCC) has been based on immunotherapy for a while with a modest efficacy (10–15 % of objective responses) and a poor tol- erance [1]. From 2006, the first antiangiogenic drugs opened the era of targeted therapies for mRCC. According to Folkman’s theory, these treatments inhibit the neoan- giogenesis and significantly increase patients’ survival [2]. Targeted therapies are expected to interact with three dif- ferent molecular pathways: the direct inhibition of VEGF and its receptor, the inhibition of the Raf/MEK/ERK pathway in the endothelial cells, and the inhibition of the PI3K/AKT/mTOR pathway in the tumor cells. Currently, seven drugs have the indication in mRCC: sunitinib, bev- acizumab in association with interferon, sorafenib, pazop- anib, axitinib, temsirolimus, and everolimus. The emergence of these new therapies targeting tumor angiogenesis has improved mRCC patients’ prognosis. P. Bigot (&) Á S. Lebdai Á A. R. Azzouzi Department of Urology, Angers University Hospital, Angers, France e-mail: pibigot@chu-angers.fr A. Ravaud Department of Oncology, Bordeaux University Hospital, Bordeaux, France J.-M. Ferrie `re Á J.-C. Bernhard Department of Urology, Bordeaux University Hospital, Bordeaux, France J.-J. Patard Department of Urology, Bice ˆtre University Hospital, Kremlin-Bice ˆtre, France 123 World J Urol DOI 10.1007/s00345-013-1060-0