Factors associated with outcome in patients with advanced renal cell carcinoma in the era of Antiangiogenic agents

Known clinical factors associated with outcome in advanced renal cell carcinoma (RCC) include performance status, disease-free interval, number of metastatic sites, and several laboratory variables such as hemoglobin, calcium, and lactate dehydrogenase. These factors were pertinent to the era of immunotherapy. Recent analysis from trials with anti-VEGF agents shows these factors continue to be of major importance. Additionally, several serum and molecular markers, many of which relate to certain alterations of the von Hippel-Lindau (VHL) pathway, are currently being investigated. Responses to VEGF-targeted agents seem to be related to a greater modulation of serum VEGF and soluble VEGF receptors levels. The impact of VHL gene status on clinical objective response to VEGF-targeted therapy was tested in a large study but was not found to predict a higher response rate to these agents. However, subsets of VHL mutations that predict a truncation of the VHL protein seem to have the best responses to these agents. Future prognostic models will incorporate molecular markers with clinical variables to refine prognosis and prediction in patients with metastatic clear-cell RCC treated with novel antiangiogenic agents. These models, if externally and prospectively validated, will rationally select patients for specific VEGF-directed therapeutic agents.