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.
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.
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.
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.
Current urology. 2021 Sep 24 [Epub]
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
Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan., Department of Urology, Hiroshima-City Asa Citizens Hospital, Hiroshima, Japan., Department of Urology, Fukuyama Medical Center, Fukuyama, Japan., Department of Urology, Hiroshima General Hospital, Hatsukaichi, Japan., Department of Urology, Hiroshima Prefectural Hospital, Hiroshima, Japan., Department of Urology, Kure Medical Center and Chugoku Cancer Center, Kure, Japan., Department of Urology, Miyoshi Central Hospital, Miyoshi, Japan., Department of Urology, Onomichi General Hospital, Onomichi, Japan., Department of Urology, Higashi-Hiroshima Medical Center, Higashi-Hiroshima, Japan.