Prognostic factors and risk classifications for patients with metastatic renal cell carcinoma

The introduction of molecular-targeted therapy has made dramatical changes to treatment for metastatic renal cell carcinoma. Currently, there are four vascular endothelial growth factor receptor-tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors in Japan. For the appropriate clinical use of these molecular-targeted drugs, the identification of prognostic and/or predictive factors in patients who received these drugs is required. Although molecular biological and genetic factors that determine the prognosis of patients with metastatic renal cell carcinoma have been reported, most of these factors are problematic in that the number of patients analyzed was small. In contrast, clinicopathological prognostic factors, including the practice of cytoreductive nephrectomy, pathological findings, metastatic sites and metastasectomy, and abnormal inflammatory response, have been identified by analyzing a relatively large number of patients. Several prognostic classification models that were developed by combining these clinicopathological factors are widely used in not only clinical trials, but also routine clinical practice. However, the quality of these prognostic models is considered to be insufficient regarding prognostic prediction of metastatic renal cell carcinoma patients and, thus, requires further improvements. Recently, basic and clinical studies have been extensively carried out for the identification of promising informative markers and for understanding molecular mechanisms of resistance to molecular-targeted drugs in metastatic renal cell carcinoma patients. The present review considers ongoing translational research efforts on clinicopathological, molecular biological, and genetic prognostic and/or predictive factors for metastatic renal cell carcinoma patients in the era of molecular-targeted therapy, and discusses the clinical implications of these findings.