Renal cell carcinoma (RCC) remains a formidable urologic malignancy, particularly in cases presenting with vascular invasion or suspected metastatic disease. Traditionally, surgery has been the mainstay of treatment for localized and locally advanced RCC. However, recent advancements in systemic therapy, especially the combination of immunotherapy and targeted therapy, have demonstrated significant clinical benefits in advanced or metastatic RCC. The concept of neoadjuvant targeted therapy and immunotherapy is still under investigation, with complete pathological response (pCR) being rarely reported in real-world settings.

A 49-year-old male with a history of hypertension presented initially with upper abdominal discomfort for approximately one month, He sought medical attention at Zhongxiao Hospital, where abdominal computed tomography (CT) revealed a left renal mass with tumor thrombus extending into the inferior vena cava (IVC), and regional lymphadenopathy. For further evaluation and a second opinion, the patient visited our urology outpatient clinic and was subsequently admitted. An ultrasound-guided biopsy of the left renal mass was performed on September 5, 2024, and pathology revealed clear cell renal cell carcinoma with sarcomatoid differentiation. Whole-body bone scan conducted on September 6, 2024, showed no definite evidence of bone metastasis. Chest CT on the same day confirmed bilateral lung nodules up to 0.4 cm, for which metastasis could not be excluded. A comprehensive renal function study on September 12, 2024, revealed split renal function with left kidney: 31 ml/min; right kidney: 191 ml/min. In view of the locally advanced disease with suspected metastasis, the patient was initiated on neoadjuvant systemic therapy with Pembrolizumab 200 mg (C1) and Lenvatinib 14 mg daily, starting on September 11, 2024. He completed four cycles of Pembrolizumab, with continued Lenvatinib throughout the treatment period. Follow-up CT imaging demonstrated tumor regression. Subsequently, the patient underwent robot-assisted left radical nephrectomy with IVC thrombectomy on November 27, 2024. Final pathology showed complete tumor necrosis with no viable malignant cells identified in the kidney, ureter, lymph nodes, or IVC margin. The pathological staging was determined as ypT0N0, indicating a complete pathological response to the neoadjuvant targeted therapy and immunotherapy.

Renal cell carcinoma with IVC thrombus and sarcomatoid features is aggressive and challenging to treat. Although Pembrolizumab plus Lenvatinib has shown high response rates in advanced RCC, complete pathological remission after neoadjuvant therapy remains rare.

This case demonstrates a rare complete pathological response (ypT0N0) in a patient with locally advanced RCC and IVC thrombus following neoadjuvant targeted therapy and immunotherapy. It highlights the potential of systemic therapy to downstage aggressive tumors prior to surgery.