From the Genitourinary Program, University of Chicago, Chicago, IL
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Walter M. Stadler, MD, FACP, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL 60637; e-mail: wstadler{at}medicine.bsd.uchicago.edu
Overview: Therapeutic options for metastatic renal cancer have expanded dramatically. The vascular endothelial growth factor (VEGF) receptor/platelet-derived growth factor receptor tyrosine kinase inhibitors sorafenib and sunitinib improve progression-free survival for patients with clear cell histology compared with placebo and interferon-alpha, respectively. Likewise, progression-free survival is improved by addition of the VEGF binding agent bevacizumab to interferon-alpha for patients with clear cell carcinoma. Benefit with these VEGF–pathway-directed agents is greatest for patients with good and intermediate prognoses; benefit for poor prognosis and non-clear cell cancers is incompletely defined. Temsirolimus improves survival of patients with poor prognosis, with some suggestion that patients with non-clear cell carcinomas have the greatest benefit; however, the value of mammalian target of rapamycin (mTOR)–pathway-directed agents for patients with good and intermediate prognoses is unknown. The value of sequential therapy with these agents is incompletely defined. The only therapy that leads to long-term complete responses is high dose interleukin-2, but only for patients with clear cell histology, with some suggestion that favorable histologic features and high carbonic anhydrase IX expression are predictive markers. Predictive markers for VEGF pathway and mTOR inhibitors have not been verified, but a number of serum, histologic, and imaging biomarkers show promise.
