Abstract
Brain (BM) and pancreatic metastases (PM) from renal cell carcinoma (RCC) represent two faces of the same coin in terms of disease course: BM are associated with shorter overall survival (OS) compared with PM. The reasons for this difference have never been investigated. This is the objective of the BRAVE project. From a few French centers, only RCC patients (pts) who underwent surgical resection or biopsy for BM or PM and with available histological tissue samples (TS) were enrolled. Medical records were retrospectively reviewed to determine patients' characteristics, prognostic factors and outcome. To identify factors which could differentiate BM and PM, we will perform: i) correlation between clinico-pathological characteristics and metastasis location (BM vs PM) ii) histopathological features description by TS review and iii) immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analyses in BM, PM and nephrectomy (Nx) TS. Out of 113 pts enrolled so far, most pts were male (67%), had clear-cell histology (98%) and underwent radical Nx (93%). Forty-seven pts (41%) underwent at least one metastasectomy (Mx) before BM or PM surgery. Sixty-two pts (55%) had BM and 51 (45%) had PM. Between BM and PM, there was no significant differences in baseline characteristics (sex, age at diagnosis of RCC, Nx, primary RCC (left vs right), histology, Fuhrmann, Mx) except for T stage: T3-T4 vs T1-T2 increased the risk of BM compared to PM (odds ratio: 4.17, 95%CI = [1.52-11.39], p < 0.01). Interestingly, time interval between initial diagnosis (Dx) and BM was shorter than that between Dx and PM (median: 4.1 vs 8.3 years, p < 0.009). The total number of deaths was 52 (46%). Pts with BM had a shorter OS than pts with PM (median: 2.7 vs 9.5 years, p < .0001). In multivariable analysis, BM and synchronous metastases were significantly associated with poor OS, whereas primary RCC in the right kidney was marginally associated with poor OS (p = 0.05). Analyses of TS are ongoing. BM and PM from RCC have a different natural history. Heterogeneity between biological markers expression inside PM and BM might explain these divergent outcomes.
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