Clear cell renal cell carcinoma

Kidney cancer subtype pages use these definitions; several rare entities are now diagnosed by molecular testing rather than appearance alone.

Patients whose kidney cancer has been removed but who are at high risk of recurrence (large or high-grade tumours, node involvement, or resected metastases) can now be offered a year of pembrolizumab, which increases the chance of being alive and cancer-free several years later. Roughly nine patients need treatment to prevent one recurrence at two years, and some will have permanent side effects, so shared decision-making matters. Why pembrolizumab succeeded where similar drugs failed is not fully understood.

Patients with newly diagnosed advanced clear-cell kidney cancer should receive an immunotherapy-based combination; lenvatinib plus pembrolizumab gives the highest response rate and longest PFS of the available options, at the cost of more side effects requiring dose adjustment. Sunitinib alone is no longer an appropriate standard. Choosing among the combinations depends on risk group, symptoms, comorbidity and the value placed on treatment-free survival, which favours nivolumab plus ipilimumab in intermediate and poor risk.

Immunotherapy plus a VEGF kinase inhibitor is a first-line standard for advanced clear cell kidney cancer in all risk groups; comparable regimens include nivolumab-cabozantinib and lenvatinib-pembrolizumab.

Nivolumab-ipilimumab is a first-line standard for intermediate- and poor-risk clear cell kidney cancer, notable for durable complete responses and treatment-free intervals.