Impact of bone and liver metastases on patients with renal cell carcinoma treated with targeted therapy.

The skeleton and liver are frequently involved sites of metastasis in patients with metastatic renal cell carcinoma (RCC). To analyze outcomes based on the presence of bone metastases (BMs) and/or liver metastases (LMs) in patients with RCC treated with targeted therapy. We conducted a review from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) of 2027 patients with metastatic RCC. We analyzed the impact of the site of metastasis on overall survival (OS) and time-to-treatment failure. Statistical analyses were performed using multivariable Cox regression. The presence of BMs was 34% overall, and when stratified by IMDC risk groups was 27%, 33%, and 43% in the favorable-, intermediate-, and poor-risk groups, respectively (p<0.001). The presence of LMs was 19% overall and higher in the poor-risk patients (23%) compared with the favorable- or intermediate-risk groups (17%) (p=0.003). When patients were classified into four groups based on the presence of BMs and/or LMs, the hazard ratio, adjusted for IMDC risk factors, was 1.4 (95% confidence interval [CI], 1.22-1.62) for BMs, 1.42 (95% CI, 1.17-1.73) for LMs, and 1.82 (95% CI, 1.47-2.26) for both BMs and LMs compared with other metastatic sites (p<0.0001). The prediction model performance for OS was significantly improved when BMs and LMs were added to the IMDC prognostic model (likelihood ratio test p<0.0001). Data in this analysis were collected retrospectively. The presence of BMs and LMs in patients treated with targeted agents has a negative impact on survival. Patients with BMs and/or LMs may benefit from earlier inclusion on clinical trials of novel agents or combination-based therapies.