Renal cell carcinoma (RCC) remains a challenging urologic malignancy, particularly in cases with vascular invasion or suspected metastasis. Recent advancements in systemic therapies, including immune checkpoint inhibitors (ICI) combined with VEGFR tyrosine kinase inhibitors (TKIs), have shown promising clinical benefits in advanced or metastatic RCC. This report presents a case of advanced RCC with complete pathological response (pCR) following ICI-based therapy.

A 49-year-old male with a history of hypertension presented in August 2024 with upper abdominal discomfort, poor appetite, and significant weight loss of more than 10 kg over the past three months. A CT scan at a local hospital revealed a left renal mass with tumor thrombus extending into the inferior vena cava (IVC) and regional lymphadenopathy. He was referred to our center, where a biopsy confirmed clear cell RCC with sarcomatoid differentiation. A bone scan was negative, and bilateral tiny lung nodules (0.4 cm) were found on chest CT. Lab results indicated anemia, thrombocytosis, low albumin, and elevated LDH, placing the patient in the IMDC intermediate-risk category. Given the advanced disease, suspected metastasis, and systemic symptoms, we recommended systemic therapy as the first-line treatment, with the possibility of deferred cytoreductive nephrectomy. Starting in September 2024, the patient tolerated well with pembrolizumab(200mg) and Lenvatinib(14 mg). After completing four cycles of treatment, follow-up CT revealed significant tumor regression, and the patient's lab results and overall performance improved. As a result, the patient underwent robot-assisted left radical nephrectomy with IVC thrombectomy. Final pathology revealed complete tumor necrosis with no viable malignant cells, with negative margins for IVC involvement and all 21 resected lymph nodes. The pathological stage was determined as ypT0N0, indicating a complete pathological response. The patient remained disease-free through follow-up until March 2025.

While ICI combined with VEGFR-TKI is the current standard treatment for advanced RCC, its role in cytoreductive nephrectomy remains unclear. In this case, the patient's substantial improvement after systemic therapy made him an ideal candidate for cytoreductive nephrectomy, ultimately achieving an impressive treatment response. Notably, sarcomatoid features, typically associated with more aggressive disease, have shown a better response to ICI therapy across various trials. Literature suggests that the complete response rate with ICI-based therapy in metastatic RCC is around 10-15%, with pT0 status in the primary tumor being rare and difficult to predict.

This case highlights the potential of ICI-based therapy to induce a complete pathological response in advanced RCC, demonstrating its ability to downstage aggressive tumors and reverse the systemic cachexia caused by malignancy, ultimately making surgery feasible.