EvidenceRenal cell carcinoma

There has been no clear standard for clear-cell kidney cancer that progresses after immunotherapy; this is the first phase 3 to show a HIF-2 alpha inhibitor combination beating a standard tyrosine kinase inhibitor on progression-free survival in that setting. Whether it changes practice depends on the final overall survival analysis and on regulators, since the interim survival difference did not reach significance and the combination brings the toxicity of two drugs.

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.

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.

Maintaining a healthy weight is now established cancer prevention for over a dozen cancer types. For clinicians and policymakers, obesity belongs alongside tobacco and alcohol in prevention strategy. Whether intentional weight loss in adulthood reverses risk is still being studied, including in trials of GLP-1 drugs.

A single biopsy is an incomplete picture of a patient's cancer. Truncal mutations shared by all cells (in kidney cancer, VHL) are the most reliable drug targets, whereas mutations in only some branches predict resistance. This is why liquid biopsy and multi-region sampling matter.

This is the study most often cited for the size of the obesity and cancer link, and it broadened the list of weight-related cancers well beyond the few known before. It underlies weight management advice in cancer prevention guidance and the current interest in whether GLP-1 drugs change cancer risk.