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  • The International Metastatic RCC Database Consortium (IMDC) and Memorial Sloan Kettering risk scores have become important tools to aid in the selection of first-line treatment of patients with metastatic clear cell renal cell carcinoma (RCC). The IMDC risk score includes the following risk factors: elevated serum corrected calcium level, anemia, Karnofsky performance score less than 80, systemic treatment for metastatic disease within 1 year, absolute neutrophil count greater than the upper limit of normal (ULN), and platelet count greater than the ULN.

  • As of 2020, contemporary first-line treatment options for metastatic RCC (mRCC) include nivolumab plus ipilimumab, pembrolizumab plus axitinib, avelumab plus axitinib, and cabozantinib. The only first-line treatments to demonstrate improved overall survival (OS) compared with sunitinib are nivolumab plus ipilimumab (CheckMate 214) and pembrolizumab plus axitinib (KEYNOTE-426).

  • Contemporary second-line or later treatment options for mRCC include cabozantinib, nivolumab, lenvatinib plus everolimus, and axitinib. There is limited prospective evidence for treatment sequencing after contemporary first-line therapies, which presents a challenge for clinicians.

  • Patients with metastatic non–clear cell RCC have inferior outcomes compared with patients with metastatic clear cell RCC, and treatment outcomes vary by histologic subgroup of non–clear cell RCC. In general, patients with metastatic non–clear cell RCC should be referred to a tertiary cancer center for enrollment in clinical trials.

  • Adjuvant treatment for locally advanced RCC is not currently standard of care. Adjuvant treatment with vascular endothelial growth factor (VEGF)–targeted therapy has not consistently improved OS. Adjuvant treatment with checkpoint inhibitors is currently being evaluated in prospective clinical trials.

  • The efficacy and timing of cytoreductive nephrectomy (CN) for patients with intermediate- or poor-risk mRCC receiving VEGF-targeted therapy were called into question by the CARMENA and SURTIME trials. At MD Anderson Cancer Center, CN is not recommended for patients with poor-risk disease, and in most patients with intermediate-risk disease, we begin with systemic therapy and reserve CN for patients with a response to treatment and good performance status.


According to the World Health Organization Global Cancer Observatory (GLOBOCAN) database, there were estimated to be 60,336 new cases of kidney cancer in the United States in 2018, and 15,333 patients were projected to die as a consequence of disease progression.1 Renal cell carcinoma (RCC) is the most common histology found in kidney tumors, with clear cell RCC (ccRCC) being the most common histologic subtype (Fig. 43–1). Non–clear cell RCC (nccRCC) subtypes include chromophobe, papillary, oncocytoma, collecting duct carcinoma, renal medullary carcinoma (RMC), translocation, and unclassified RCC.


Photomicrographs of clear cell (conventional) renal cell carcinoma (RCC) with low-grade (A) and high-grade (B) nuclear features. Photomicrographs of a type 1 papillary RCC (C) showing papillae lined by short cuboidal cells and a type 2 papillary RCC (D) showing papillae lined by tall columnar cells, with eosinophilic cytoplasm and high-grade nuclear features. (Used with permission from Pheroze Tamboli, MD.)

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