The evolving role of surgery for advanced renal cell carcinoma in the era of molecular targeted therapy.
OBJECTIVE
Thoughtful integration of surgical and medical approaches to metastatic renal cell carcinoma is paramount for maximizing disease control. Accomplishing this in the current era of targeted molecular therapies presents unique challenges and opportunities.


METHODS
A systematic review of the MEDLINE and PubMed databases, and relevant urological and oncological journals was performed pertaining to cytoreductive nephrectomy, metastasectomy, targeted molecular therapies for renal cell carcinoma, and neoadjuvant and adjuvant approaches to the management of advanced renal cell carcinoma.


RESULTS
Cytoreductive nephrectomy provides an overall survival advantage in select patients with metastatic renal cell carcinoma who receive subsequent interferon-alpha. However, cytokine therapies are now being supplanted by targeted molecular approaches that block the effects of vascular endothelial growth factor and other molecular events. Although cytoreductive nephrectomy remains a standard of care, limited insight into the biological effects of nephrectomy on mechanisms such as immunoregulation and angiogenesis precludes definitive statements about how to integrate surgery and targeted agents. Ongoing investigation involving basic science and translational research is required to optimize the integration of these approaches. Adjuvant and neoadjuvant vascular endothelial growth factor targeted approaches to renal cell carcinoma are now also being explored and the unique side effects of these agents, including potential effects on wound healing and vascular integrity, require careful consideration.


CONCLUSIONS
Integrated approaches involving surgery and vascular endothelial growth factor targeted therapies hold much promise for the management of advanced renal cell carcinoma. Prospective clinical testing with vigilant attention to the risk-benefit ratio and thoughtful evaluation of biological correlates are required to optimize these approaches.
Rini
Brian I
BI
Department of Solid Tumor Oncology and Urology, Cleveland Clinic Taussig Cancer Center and Section of Urological Oncology, Glickman Urological Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Campbell
Steven C
SC
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000473:pathology / Q000628:therapy*; D009392:Nephrectomy; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D007372:Interferons; D040262:Receptors, Vascular Endothelial Growth Factor