Impact of Bone and Liver Metastases on Patients with Renal Cell Carcinoma Treated with Targeted Therapy

Abstract

Background The skeleton and liver are frequently involved sites of metastasis in patients with metastatic renal cell carcinoma (RCC). Objective The purpose of this study was to analyze outcomes based on the presence of bone metastases (BM) and/or liver metastases (LM) in patients with RCC treated with targeted therapy. Design, Setting and Participants We conducted a review from the International Metastatic RCC Database Consortium (IMDC) of 2,027 patients with metastatic RCC. Outcome Measurements and Statistical Analysis We analyzed the impact of site of metastasis on overall survival (OS) and time-to-treatment failure (TTF). Statistical analyses were performed using multivariable Cox regression. Results and Limitations Presence of BM was 34% overall and when stratified by IMDC risk groups was 27%, 33%, and 43% in favorable, intermediate, and poor-risk groups, respectively (pitalic>0.001). Presence of LM was 19% overall and higher in the poor-risk patients (23%) compared to the favorable or intermediate-risk groups (17%) (p=0.003). When patients were classified into four groups based on the presence of BM and/or LM the hazard ratio (HR), adjusted for IMDC risk factors, was 1.4 (95% Confidence Interval (CI) 1.22–1.62) for BM, 1.42 (95% CI 1.17–1.73) for LM, and 1.82 (95% CI 1.47–2.26) for both BM and LM compared to other metastatic sites (pbold>0.0001). The prediction model performance for OS was significantly improved when BM and LM were added to the IMDC prognostic model (likelihood ratio test p<0.0001). Data in this analysis was collected retrospectively. Conclusions The presence of BM and LM in patients treated with targeted agents has a negative impact on survival. Patients with BM and/or LM may benefit from earlier inclusion on clinical trials of novel agents or combination-based therapies.

RANK/OPG ratio of expression in primary clear-cell renal cell carcinoma is associated with bone metastasis and prognosis in patients treated with anti-VEGFR-TKIs

“…RR on sunitinib was 35% and 55%, respectively (Beuselinck et al, 2011). The impact of the presence of BM on RR and/or mOS was confirmed in subsequent publications (Patil et al, 2011;Motzer et al, 2013;McKay et al, 2014).…”

Cabozantinib for the treatment of renal cell carcinoma

“…OS and PFS were increased with cabozantinib compared to everolimus (HR < 1) for all subgroups analyzed including those defined by MSKCC risk groups, the number of prior VEGFR TKIs, duration of prior VEGFR-TKI treatment, prior sunitinib or pazopanib therapy, prior treatment with checkpoint inhibitors targeting PD-1, and MET expression level. Prolongation of OS and PFS with cabozantinib was also observed irrespective of tumor burden or metastatic site, including in patients with bone metastases, which are associated with a poor prognosis [33].…”

“…Improvement in PFS and OS with cabozantinib was maintained in all reported subgroups, including in patients with bone metastases, suggesting that cabozantinib is a broadly applicable treatment option. Bone metastases are prognostic for poor outcomes in patients with advanced RCC, and treatment for these patients is an unmet medical need [33].…”

Impact of neutrophil-to-lymphocyte ratio on effects of targeted therapy for metastatic renal cell carcinoma patients with extrapulmonary metastasis

“…20 In a review from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), bone and liver metastases have been reported as predictive factors for poor prognosis. 21 Brain metastasis in mRCC was associated with poor prognosis, but improved compared with that in the era of cytokine therapy. 22 This evidence indicates the importance of considering the metastatic status in predicting the therapeutic effect in mRCC cases.…”