Over the past years, the therapy for patients with advanced/metastatic CCRCC has considerably evolved and new therapeutic options are now available for these patients, including targeted agents such as those targeting the VEGF pathway (mainly represented by VEGFR-directed tyrosine kinase inhibitors, TKIs) or targeting mTOR (such as everolimus) or immunotherapy based on immune checkpoint inhibitors and combination treatment strategies [183]. This evidence concerns the gene VEGFA and nonpapillary renal cell carcinoma.