In October 2019, a 67-year-old man was admitted to our hospital due to left flank pain. He was initially diagnosed with a left renal tumor based on ultrasound examination. The patient had a history of controlled hypertension for approximately 10 years, but no personal or family history of other systemic disorders. Contrast-enhanced computed tomography (CT) revealed the presence of a malignant mass (5.2 cm x 4.3 cm) ( Figures 1A, B ). Chest CT revealed multiple nodules in the right lower lung, indicating metastasis ( Figure 1C ). Whole-body bone scanning by emission CT suggested vertebral (T12) metastasis ( Figure 1D ). The Eastern Cooperative Oncology Group score of the patient was 1. Routine blood and blood biochemistry tests did not yield abnormal findings. Based on these findings, the patient was diagnosed with advanced left renal carcinoma graded cT2NxM1.
According to the criteria established by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), the prognostic risk associated with one risk factor was intermediate. Thus, cytoreductive nephrectomy was recommended, and pathological examination confirmed CDC ( Figure 2A ). Immunohistochemistry was used to examine the presence of several key markers: paired box 8-negative (PAX8; positive), p63 (negative), CD10 (negative), and vinculin (positive) ( Figures 2B-E ). Immunohistochemistry was positive for programmed cell death 1 ligand 1 (PD-L1) ( Figure 2F ). Next, we performed genetic profiling using a customized panel consisting of 618 genes to investigate potential actionable somatic and pathogenic germline variants ( Supplemental Table 1 ). Sequencing analysis did not identify pathogenic or likely pathogenic germline variants in this sample. However, four somatic alterations with uncertain clinical significance were detected: ERBB receptor feedback inhibitor 1 (ERRFI1) S138fs; speckle type BTB/POZ protein (SPOP) S55fs; E1A binding protein p300 (EP300) S457I; and TEK receptor tyrosine kinase (TEK) R673H. However, none of these findings supported the potential response to any of the therapies approved by the Food and Drug Administration. We recommended a treatment strategy involving the combination of a targeted agent and ICI, which has shown excellent therapeutic results in the treatment of ccRCC. The patient was fully informed and aware of the off-label use of the drugs. Pazopanib (400 mg, per os, once daily) and the PD-1 monoclonal antibody camrelizumab (200 mg, intravenous gtt, once every 3 weeks) were administered. Following one cycle of therapy, the patient experienced a reduction in appetite and developed severe drug-induced hepatic injury. However, chest CT showed remarkable shrinkage of the metastases, indicating a partial response ( Figures 3A, B ). Subsequently, glucocorticosteroid therapy was administered. Liver function recovered three weeks later. Immunotherapy was discontinued, and monotherapy with pazopanib was initiated.
Five months later, the patient presented with cough, dyspnea, and lumbar pain. Chest CT showed malignant pleural effusion and pleural metastasis ( Figure 3C ); this was confirmed by the cytological examination of pleural effusion. Considering the response of the patient to the previous combination strategy, axitinib (5 mg, per os, twice daily) and the PD-1 monoclonal antibody sintilimab (200 mg, intravenous gtt, once every 3 weeks) were duly administered. The symptoms of the patient were gradually alleviated and completely disappeared after five cycles of treatment. Except for hypertension, there was no occurrence of obvious adverse reactions. Chest CT revealed a marked reduction of pleural effusion ( Figure 3D ). In April 2021, after 11 months of treatment, examinations confirmed the complete disappearance of the metastatic lesion in the lung. The last follow-up examination was performed in July 2021. Chest and abdomen CT did not reveal the presence of abnormal lesions ( Figure 3E ) and demonstrated improvement in the osteogenic structure at the site of vertebral metastasis ( Figure 3E ). The patient had an excellent physical status that was similar to that of a healthy person. Thereafter, the patient remained tumor-free for >14 months after receiving the combination therapy ( Figure 4 ).
Radiological examination at initial visit. (C) Chest CT scan showing metastatic nodules in the right lower lung.