关键词: 肾透明细胞癌, 免疫治疗, 靶向治疗

Abstract:

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma. Patients classified as intermediate- or poor-risk according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), particularly those with multiple organ metastases, generally have an unfavorable prognosis. Here, we report a case of advanced ccRCC in an IMDC poor-risk patient who achieved an unexpectedly prolonged survival with combination therapy followed by maintenance immunotherapy. A 65-year-old male developed multiple metastases involving the lungs, liver, and bone shortly after undergoing radical nephrectomy for right-sided renal cancer. Laboratory findings revealed anemia, neutrophilia, and thrombocytosis, and the IMDC score was 5, indicating poor-risk disease. The patient received first-line treatment with the programmed death-ligand 1 (PD-L1) inhibitor benmelstobart in combination with the multi-target tyrosine kinase inhibitors (TKIs) anlotinib. After 6 weeks of therapy, radiological evaluation demonstrated a partial response (PR), with an overall tumor reduction of approximately 48%. Subsequent imaging assessments confirmed a durable PR, accompanied by significant improvement in clinical symptoms and performance status. During treatment, the patient developed progressive proteinuria, with a maximum 24-hour urinary protein level of 5.18 g. Despite stepwise dose reduction of anlotinib, proteinuria recurred, necessitating discontinuation of the TKIs. Following cessation of anlotinib, the patient continued benmelstobart monotherapy as maintenance therapy and maintained sustained deep remission. After approximately 3 years of treatment, serum creatinine levels gradually increased, reaching a peak of 228 μmol/L. Considering the possibility of treatment-related renal toxicity and the durable disease control achieved, immunotherapy was subsequently discontinued. No further antitumor treatment was administered. The patient eventually experienced disease progression and died in September 2024, with an overall survival of 44 months. This case suggests that the combination of benmelstobart and anlotinib can induce rapid and durable antitumor responses in patients with IMDC poor-risk advanced ccRCC. Notably, in patients who respond well to combination therapy, discontinuation of TKIs due to intolerable adverse events followed by maintenance immunotherapy may still provide long-term disease control. This sustained benefit may be associated with tumor microenvironment remodeling and the establishment of immunological memory induced by anti-angiogenic therapy. Furthermore, this case highlights the importance of vigilant monitoring of renal toxicity and individualized treatment adjustment during combined targeted therapy and immunotherapy.

Key words: Clear cell renal cell carcinoma, Immunotherapy, Targeted therapy