Potential confounding factors may include, for example, differences in age, metastatic burden, RCC histology, performance status, response to first VEGF TKI, lab values (e.g., neutrophil count, platelet count, corrected calcium level) or composite risk scores (e.g., MSKCC or Heng et al. criteria). The gene discussed is VEGFA; the disease is renal cell carcinoma.