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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Clear cell is the common kidney cancer, driven by loss of the VHL gene that leaves the tumour behaving as if starved of oxygen and flooding itself with blood vessels. That biology explains why anti-angiogenic drugs, immunotherapy and the HIF-2 alpha blocker belzutifan all work.
Clear cell renal cell carcinoma arises from the proximal tubule and in about nine in ten cases has lost the VHL gene on chromosome 3p, stabilising HIF-2 alpha and driving VEGF, so tumours are highly vascular; PBRM1, SETD2 and BAP1 mutations shape its behaviour. Small tumours are removed by partial nephrectomy or ablated, and some are watched. Adjuvant pembrolizumab after nephrectomy improves survival in higher-risk disease (KEYNOTE-564). Metastatic disease is treated first line with an immunotherapy doublet: pembrolizumab with axitinib or lenvatinib, nivolumab with cabozantinib, or nivolumab with ipilimumab for intermediate- and poor-risk patients; cabozantinib, axitinib, tivozanib and belzutifan follow. Belzutifan, the first HIF-2 alpha inhibitor, was approved for VHL disease in 2021 and for previously treated advanced disease in 2023. Cytoreductive nephrectomy is now reserved for selected patients after CARMENA.
| Setting | Approach | Guideline |
|---|---|---|
| Small renal mass | Partial nephrectomy, thermal ablation or active surveillance by size, growth and patient fitness. | not mapped |
| Localised, higher risk | Radical or partial nephrectomy followed by one year of adjuvant pembrolizumab (KEYNOTE-564, overall survival benefit). | not mapped |
| Metastatic, first line | Pembrolizumab plus axitinib (KEYNOTE-426) or lenvatinib, nivolumab plus cabozantinib, or nivolumab plus ipilimumab (CheckMate 214) for intermediate and poor risk; cytoreductive nephrectomy only in selected patients. | not mapped |
| Later lines | Cabozantinib, axitinib, belzutifan (LITESPARK-005), lenvatinib plus everolimus, tivozanib. | not mapped |
| VHL disease | Belzutifan for kidney, pancreatic and CNS tumours that would otherwise need surgery; surveillance of the kidneys with nephron-sparing surgery when tumours reach 3 cm. | not mapped |