Very Late Recurrence of Clear Cell Renal Cell Carcinoma With Pancreatic and Hepatic Metastases Showing Durable Response to Dual Checkpoint Blockade

Very late recurrence of clear cell renal cell carcinoma with pancreatic involvement is uncommon, and treatment and toxicity management are not well defined. A patient developed liver and pancreatic lesions approximately 18 years after nephrectomy for clear cell renal cell carcinoma. Liver biopsy with immunohistochemistry confirmed metastatic renal origin; the pancreatic mass was diagnosed radiologically. Nivolumab plus ipilimumab (four induction cycles) followed by nivolumab maintenance induced a partial response. During maintenance, the patient experienced an immune-related endocrine adverse event with secondary adrenal insufficiency and central hypothyroidism, managed with hormone replacement without treatment interruption. Performance status remained excellent, and tumor response has been durable for more than 30 months. This case highlights that endocrine immune-related adverse events can be safely managed with appropriate hormone replacement, allowing uninterrupted immunotherapy and preserving long-term benefit. Dual immune checkpoint blockade can achieve durable disease control in very late recurrent clear cell renal cell carcinoma with pancreatic and hepatic metastases, and endocrine toxicity may be safely managed to maintain benefit.