Long-term survival with immune checkpoint inhibitors combined with bevacizumab in advanced clear cell renal cell carcinoma

Rationale: Renal cell carcinoma is a highly heterogeneous urological malignancy, with clear cell renal cell carcinoma (ccRCC) as the most common pathological subtype. A considerable proportion of patients are diagnosed at advanced stages or experience postoperative recurrence and distant metastasis, leading to poor long-term prognosis. Although targeted therapy and immune checkpoint inhibitors (ICIs) have greatly improved the treatment landscape of advanced ccRCC, optimal sequential and combination treatment strategies for heavily pretreated metastatic patients remain to be further explored. Patient concerns: A 49-year-old male patient was diagnosed with stage IV ccRCC complicated with lung metastasis. After palliative nephrectomy and multiple lines of targeted and immunotherapeutic regimens, the patient still suffered from continuous tumor progression, with recurrent pulmonary metastatic lesions, newly occurring adrenal metastasis and brain metastasis, accompanied by clinical symptoms including cough, hemoptysis, and persistent dizziness. Diagnoses: The patient was definitively diagnosed with metastatic ccRCC (T1N1M1, Stage IV). Radiological examinations confirmed progressive pulmonary metastases, new right adrenal metastasis, and right frontal lobe brain metastasis after multiple lines of treatment. Interventions: The patient initially underwent palliative left nephrectomy and sequential sorafenib targeted therapy. After disease progression, intracranial intensity-modulated radiotherapy combined with sunitinib plus interleukin-2 immunotherapy was administered. Following subsequent disease progression, the patient received 4 cycles of camrelizumab combined with bevacizumab, followed by bevacizumab maintenance therapy. Since January 2024, the patient has been treated with tislelizumab plus bevacizumab combination regimen. Outcomes: After sequential multi-line individualized treatment, the patient achieved sustained stable disease. The overall survival of the patient has reached approximately 6 years up to the latest follow-up, with favorable long-term survival benefit and well-tolerated treatment safety. Lessons: For heavily pretreated metastatic ccRCC patients with prior targeted therapy but no previous ICI exposure, ICI combined with bevacizumab is a feasible and effective salvage treatment regimen, which can achieve durable survival benefits. Further prospective clinical studies and long-term follow-up are required to verify the clinical promotion value of this combination strategy.