Systemic Therapy for Metastatic Renal-Cell Carcinoma

Until recently, there was a dearth of effective systemic therapies for kidney cancer. The incidence of the disease steadily increased from 1975 through 2008 and leveled off after 2008.(1-3) Currently, it is among the 10 most frequently diagnosed cancers in men and women in the United States, with more than an estimated 62,000 new cases in 2016.(4) The prognosis has historically been poor, with current 5-year survival rates of 74% overall, decreasing to 53% among patients with locoregional (stage III) disease and 8% among patients with metastatic disease. 1,3 Kidney cancer is a disease of the middle-aged and elderly: 91% of patients receive a diagnosis at 45 years of age or older, and 48% receive a diagnosis at 65 years of age or older. (1) Renal-cell carcinoma, the most common form of kidney cancer, occurs in 90% of cases and is nearly twice as common in men as in women. (3) The 5-year survival rate among patients with kidney cancer increased from 57% in 1987-1989 to 74% in 2006-2012(1); this increase was attributable in part to a higher proportion of indolent and low-stage tumors identified using improved early-detection techniques. (5) Still, one third of patients with kidney cancer present with regional or distant metastases, (1) and of patients with localized renal-cell carcinoma treated with nephrectomy with curative intent, approximately one quarter have relapses in distant sites. (6-8) Distant metastases occur most often in the lungs, lymph nodes, liver, bone, and brain. (9) Although more than 14,000 patients die from kidney cancer each year,(4) we have seen considerable progress in the systemic treatment of metastatic renal-cell carcinoma in the past 20 years.(10) Researchers have achieved a better understanding of the pathogenesis of the most common type of renal-cell carcinoma, clear-cell renal-cell carcinoma. This understanding has led to new agents, expanded treatment options, and increased rates of survival.