Imaging response assessment in metastatic renal cell carcinoma: a radiologist’s guide to contemporary therapeutic strategies

Renal cell carcinoma (RCC) is increasingly managed with a broad range of systemic and local therapies, creating new challenges for imaging-based response assessment in metastatic disease. While conventional size-based criteria such as RECIST v1.1 remain widely used, they incompletely capture the diverse morphologic and functional changes induced by modern treatment. Targeted therapies, including vascular endothelial growth factor receptor tyrosine kinase inhibitors and other pathway-directed agents, may produce necrosis, devascularisation, and prolonged disease stability without substantial tumour shrinkage. Immune checkpoint inhibitors introduce additional atypical response patterns, including pseudoprogression, mixed response, and rarely hyperprogression, which can complicate early interpretation of surveillance imaging. Combination regimens may demonstrate features of both targeted and immune-mediated response. In parallel, stereotactic body radiotherapy has emerged as an important treatment for oligometastatic and oligoprogressive RCC, with imaging appearances that may include lesion shrinkage, stability, or transient enlargement following treatment. This review summarises the current treatment landscape for metastatic RCC and the imaging manifestations of response across chemotherapy, targeted therapy, immunotherapy, combination systemic therapy, and stereotactic radiotherapy. It discusses the strengths and limitations of conventional and modified response criteria, including RECIST v1.1, iRECIST, attenuation-based CT criteria, and morphology-based approaches. The review also highlights the evolving role of functional and novel imaging techniques, including diffusion-weighted whole-body MRI, dual-energy and spectral CT, and PET/CT, as potential tools for improving response assessment beyond size alone. In addition, key imaging features of treatment-related toxicity are reviewed. Familiarity with these response patterns and complications is essential for radiologists involved in the care of patients with metastatic RCC, particularly as treatment strategies become increasingly multimodal and biologically complex.