BACKGROUND
A durable complete response, or sustained disappearance of measurable malignancy, can occur in selected patients with metastatic renal cell carcinoma after systemic therapy. Clear cell renal cell carcinoma is the most common renal cell carcinoma subtype. Lenvatinib is a multikinase inhibitor with antiangiogenic activity, and pembrolizumab is an anti-programmed death-1 immune checkpoint inhibitor. Although this combination can induce deep extracranial responses, central nervous system relapse after prolonged complete response remains incompletely characterized. This report describes a 73-year-old man with late isolated brain metastasis of clear cell renal cell carcinoma after durable complete response to lenvatinib-pembrolizumab and deferred cytoreductive nephrectomy.
CASE REPORT
A 73-year-old man presented with right flank pain. Computed tomography showed a right renal tumor, level II inferior vena cava tumor thrombus, and multiple pulmonary metastases. Baseline brain computed tomography showed no intracranial metastasis. He received lenvatinib plus pembrolizumab, resulting in marked regression of the primary tumor, inferior vena cava thrombus, and lung metastases. Deferred cytoreductive nephrectomy with thrombectomy was then performed, and pathology confirmed clear cell renal cell carcinoma with extensive treatment effect. Lenvatinib was discontinued because of renal dysfunction, and pembrolizumab monotherapy was continued. The patient maintained complete extracranial radiographic remission for more than 2 years. He later developed headache, and brain magnetic resonance imaging revealed a solitary left occipital metastasis without systemic recurrence. Stereotactic body radiotherapy achieved local control.
CONCLUSIONS
This case shows that late isolated central nervous system relapse can occur despite durable extracranial complete response after lenvatinib-pembrolizumab and deferred cytoreductive nephrectomy. New neurological symptoms in long-term responders should prompt brain magnetic resonance imaging, because intracranial progression may occur even when systemic imaging remains negative.

Keywords: Case Reports; Central Nervous System Neoplasms; Immune Checkpoint Inhibitors; Oncology; Renal Cell Carcinoma; Tyrosine Kinase Inhibitors