Abstract
Clear cell renal cell carcinoma (ccRCC) most commonly metastasizes to the lungs, bones, liver, and brain, whereas peritoneal involvement is exceedingly rare and typically associated with aggressive disease and poor prognosis. Although the combination of immune checkpoint inhibitors and tyrosine kinase inhibitors has significantly improved outcomes in metastatic ccRCC, reports documenting substantial pathological responses following these regimens remain limited. We describe the case of a 31‐year‐old male initially diagnosed with localized ccRCC (pT3aN0M0) after presenting with spontaneous retroperitoneal hemorrhage and undergoing radical nephrectomy. Seven months later, he developed progressive ascites and was restaged with extensive multicompartment recurrence, including peritoneal metastases, hepatic lesions, retroperitoneal lymphadenopathy, and tumor thrombus in the infrahepatic inferior vena cava. The patient was classified as poor risk according to the International Metastatic RCC Database Consortium criteria. Systemic therapy with pembrolizumab and lenvatinib was initiated, resulting in greater than 50% radiologic tumor reduction and marked clinical improvement after 14 cycles. Following this favorable response, complete cytoreductive surgery targeting all affected compartments was performed. Histopathological examination revealed extensive tumor necrosis with less than 1% residual viable tumor, confined to a single hepatic segment. The patient remains asymptomatic under close surveillance. To our knowledge, this is the first reported case of ccRCC with multicompartment metastatic disease involving peritoneal carcinomatosis treated with pembrolizumab plus lenvatinib followed by complete cytoreductive surgery, achieving near‐complete pathological response, highlighting the potential of multimodal strategies in selected patients with advanced disease.