How Metastatic Sites Shape First-Line Urgency

Terence W. Friedlander, MD, of UCSF Helen Diller Family Comprehensive Cancer Center tells Elizabeth R. Plimack, MD, MS, of Fox Chase Cancer Center that simply counting metastatic sites is not a helpful way to assign first-line therapy in advanced renal cell carcinoma (RCC), unless a single site can be removed or irradiated. What matters to him is where the disease is and what it is doing. Bone metastases worry him because they cause pain in perhaps a third to half of patients and raise fracture risk in weight-bearing areas. Liver involvement adds urgency because liver dysfunction can complicate tyrosine kinase inhibitor (TKI) use, and he urges brain imaging whenever disease volume is high. He notes that the CLEAR study showed benefit with lenvatinib plus pembrolizumab across lung, bone, and liver subgroups. Higher-risk sites push him toward immunotherapy plus a TKI, while a handful of lung metastases may allow dual immunotherapy, always guided by the patient’s goals.