RT Book, Section A1 Crona, Daniel J. A1 Cipriani, Amber B. A2 DiPiro, Joseph T. A2 Yee, Gary C. A2 Posey, L. Michael A2 Haines, Stuart T. A2 Nolin, Thomas D. A2 Ellingrod, Vicki SR Print(0) ID 1182477131 T1 Renal Cell Carcinoma T2 Pharmacotherapy: A Pathophysiologic Approach, 11e YR 2020 FD 2020 PB McGraw-Hill Education PP New York, NY SN 9781260116816 LK accesspharmacy.mhmedical.com/content.aspx?aid=1182477131 RD 2024/03/29 AB KEY CONCEPTSRenal cell carcinoma (RCC) predominantly occurs later in life, with about 70% of all cases diagnosed between the ages of 55 and 84 years.Established risk factors for RCC include smoking, obesity, hypertension, and inherited susceptibility.Inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) is the hallmark of the most common type of RCC, the clear cell histologic subtype.More than 50% of RCC cases are diagnosed by incidental findings on routine imaging for unrelated reasons.The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Criteria classifies patients into favorable-, intermediate-, and poor-risk groups based on five clinical factors, and can predict survival among both untreated patients and those treated with immunotherapy and/or targeted agents.Surgical excision of the primary tumor, either by radical or partial nephrectomy, is the preferred treatment modality for patients with stage I-III RCC, but some patients with stage IV disease may also benefit from surgery.Historically, immunotherapy (interleukin [IL]-2 and interferon [IFN]-α) were considered preferred first-line therapies for metastatic RCC (mRCC), but have largely been replaced by immune checkpoint inhibitors and targeted agents because of their improved efficacy and tolerability.First-line treatment options for mRCC are chosen based on patient-specific factors and include small molecule tyrosine kinase inhibitors (sunitinib, pazopanib, axitinib, cabozantinib), an mTOR inhibitor (temsirolimus) and immune checkpoint inhibitors (ipilimumab plus nivolumab and pembrolizumab plus axitinib).In patients who progress after first-line treatment, the multikinase inhibitors sorafenib, cabozantinib, axitinib, and lenvatinib (in combination with everolimus) are the preferred options. Immunotherapy with nivolumab has also demonstrated clinical efficacy in the second-line setting, and combination immunotherapy with a multikinase inhibitor (eg, pembrolizumab plus axitinib) is an option.