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

Background: The skeleton and liver are frequently involved sites of metastasis in patients with metastatic renal cell carcinoma (RCC).

Objective: To analyze outcomes based on the presence of bone metastases (BMs) and/or liver metastases (LMs) in patients with RCC treated with targeted therapy.

Design, Setting, And Participants: We conducted a review from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) of 2027 patients with metastatic RCC.

Outcome Measurements And Statistical Analysis: 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.

Results And Limitations: 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.

Conclusions: 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.