Combined Immunotherapy and Tyrosine Kinase Inhibitor Treatment for Metastatic Renal Cell Carcinoma With Unknown Primary Origin: A Report of Two Cases and Literature Review

Abstract

Background/aim: Renal cell carcinoma (RCC) of unknown primary origin is rarely identified and accounts for only 5% of cancers of unknown primary origin (CUP). The disease prognosis is typically poor because of no standard and effective therapy. Our review indicated that 23 cases have been reported and treated with conventional chemotherapy or tyrosine-kinase inhibitors alone; accordingly, most patients showed partial response or progression diseases with short survival time.

Case report: Herein, we present two cases of metastatic RCC of unknown primary origin. One case was papillary type and the other was clear cell type. According to the recent clinical trials in patients with metastatic RCC, a combination of immunotherapy and tyrosine-kinase inhibitors exhibited better response than conventional therapy or tyrosine-kinase inhibitors alone. Both present cases accepted a combination treatment with immunotherapy and tyrosine-kinase inhibitor and showed stable diseases. The radiological progression-free time for the case with metastatic papillary RCC was 5 months, and that with clear cell RCC was 6 months until now.

Conclusion: The combination of immunotherapy and tyrosine-kinase inhibitors is at least as effective as a tyrosine-kinase inhibitor alone, and superior to conventional chemotherapy for treating metastatic RCC of unknown primary origin.

Keywords: Case report; immunotherapy; renal cell carcinoma; unknown primary origin.

Figure 1. Histology of the biopsy. (A) Case 1: Hematoxylin and eosin (HE) stain of the lymph node biopsy exhibited large epithelioid tumor cells with ovoid nuclei, occasional prominent nucleoli, eosinophilic cytoplasm, and arranged in a mixed acinar, papillary, and infiltrating pattern. (B) Case 2: HE stain of the biopsy of bone lesions revealed epithelioid tumor cells with clear cytoplasm and oval nuclei in a delicate vascular stroma.

Figure 2. Case 1. (A-D) a series of computed tomography (CT) scans depicting the retroperitoneal lymphadenopathy of patient 1 throughout the treatment course. (A) the initial state, (B) at 3-month follow-up, (C) at 6-month follow-up, and (D) at 9-month follow-up after the initial diagnosis. The retroperitoneal lymph node size (arrowhead) remained stable after the initiation of cabozantinib+nivolumab, while the size of the inferior vena cava thrombus slightly decreased following combination therapy (asterisk). (E) Displays the absence of ascites at initial diagnosis. (F) The presence of ascites (arrow) and omental cake (triangle) 5 months after initial diagnosis, which prompted us to add ipilimumab under the impression of disease progression.

Figure 3. Case 2. A series of computed tomography (CT) scans showing the spine metastasis over the course of treatment. (A) at the initial state, (B) at the 3-month follow-up, (C) at the 7-month follow-up, and (D) at the 1-year follow-up after the initial diagnosis. The bone metastasis of lumbar 4 (arrow) remained stable during the treatment period.