Prediction of early progression of metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitor

Jun Teishima; Daiki Murata; Shogo Inoue; Tetsutaro Hayashi; Koji Mita; Yasuhisa Hasegawa; Masao Kato; Mitsuru Kajiwara; Masanobu Shigeta; Satoshi Maruyama; Hiroyuki Moriyama; Seiji Fujiwara; Akio Matsubara

doi:10.1097/CU9.0000000000000042

Prediction of early progression of metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitor

Curr Urol. 2021 Dec;15(4):187-192. doi: 10.1097/CU9.0000000000000042. Epub 2021 Sep 24.

Authors

Affiliations

¹ Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
² Department of Urology, Hiroshima-City Asa Citizens Hospital, Hiroshima, Japan.
³ Department of Urology, Fukuyama Medical Center, Fukuyama, Japan.
⁴ Department of Urology, Hiroshima General Hospital, Hatsukaichi, Japan.
⁵ Department of Urology, Hiroshima Prefectural Hospital, Hiroshima, Japan.
⁶ Department of Urology, Kure Medical Center and Chugoku Cancer Center, Kure, Japan.
⁷ Department of Urology, Miyoshi Central Hospital, Miyoshi, Japan.
⁸ Department of Urology, Onomichi General Hospital, Onomichi, Japan.
⁹ Department of Urology, Higashi-Hiroshima Medical Center, Higashi-Hiroshima, Japan.

Abstract

Background: There are various alternative first-line therapeutic options besides tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). To inform therapeutic decision-making for such patients, this study aimed to identify predictive factors for resistance to TKI.

Materials and methods: A total of 239 cases of mRCC patients who received first-line TKI therapy were retrospectively studied. Patients with a radiologic diagnosis of progressive disease within 3 months after initiating therapy were classified as primary refractory cases; the others were classified as non-primary refractory cases. The association between primary refractory cases and age, gender, pathology findings, serum c-reactive protein (CRP) level, metastatic organ status, and 6 parameters defined by the International Metastatic Renal Cell Carcinoma Database Consortium were analyzed.

Results: Of 239 cases, 32 (13.3%) received a radiologic diagnosis of progressive disease within 3 months after initiating therapy. The rates of sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, presence of liver metastasis, anemia, and time from diagnosis to treatment interval of less than a year were significantly higher in the primary refractory group. Multivariate analysis showed that sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, and liver metastasis were independently associated with primary refractory disease. A risk-stratified model based upon the number of patients with these factors indicated rates of primary refractory disease of 4.0%, 10.1%, and 45.0% for patients with 0, 1, and 2 or more factors, respectively.

Conclusions: Sarcomatoid differentiation, hypercalcemia, an elevated serum CRP level, and presence of liver metastasis were associated with primary refractory disease in mRCC patients receiving first-line TKI therapy. These results provide clinicians with useful information when selecting a first-line therapeutic option for mRCC patients.

Keywords: Metastatic renal cell carcinoma; Overall survival; Predictive factor; Tyrosine kinase inhibitor.