First-line therapy for metastatic renal cell carcinoma

Objectives: To evaluate current first-line treatment strategies in advanced or metastatic renal cell carcinoma (RCC), and to review other promising treatments under investigations. Materials and methods: We reviewed all relevant pivotal first-line systemic therapy trials, and studies investigating the role of cytoreductive nephrectomy, metastectomy, and ablative radiotherapy in advanced or metastatic RCC. Results: In total we identified 21 relevant studies, investigating both systemic and non-systemic therapies, including treatments under investigations. Conclusion: Metastatic RCC (mRCC) is a highly heterogeneous disease that is notoriously difficult to treat, however, the discovery of novel targeted therapies over the past decade have revolutionised its management. The International mRCC Database Consortium (IMDC) is a prognostic model that is commonly used in both clinical trials and routine clinical care to risk-stratify patients with mRCC, which has helped with therapy selection for mRCC patients over the past decade. However, with an improved understanding of tumour biology and genetics, this has prompted a shift from cytokine therapy to receptor tyrosine kinase inhibitors, and now to Immune Checkpoint Inhibitors (ICIs). Recent promising results from clinical studies with ICI combination treatments have transformed the treatment landscape for the management of intermediate- and poor- risk clear cell RCC, however, further research is still needed for favourable-risk, and non-clear cell patients.