Effect of glandular metastases on overall survival of patients with metastatic clear cell renal cell carcinoma in the antiangiogenic therapy era

Abstract

Background: Glandular metastases (GMs) (pancreas, breast, parotid, thyroid, or contralateral adrenal) are rare in metastatic clear cell renal cell carcinoma (mccRCC). In a multicenter study we have assessed outcome from mccRCC with or without GMs.

Patients and methods: Patients with mccRCC and GM or non-GM (NGM) at first presentation of mccRCC, treated at 9 European centers (5 French, 3 UK, and 1 Belgian centers) between January 2004 and October 2013, were retrospectively analyzed. Association between overall survival (OS) and site of metastases was assessed using the log-rank test for univariate analysis and the chi-square test for multivariable Cox regression.

Results: In all, 138 patients with GM mccRCC and 420 with NGM mccRCC were included; 37.2% patients with GM had Memorial Sloan-Kettering Cancer Center (MSKCC)-favorable risk vs. 18% NGM patients; 10.7% patients with GM had MSKCC-poor risk vs. 27% NGM patients (P<0.0001). Median interval from metastases to treatment was 4.2 months (range: 0-221.3mo). Median OS was 61.5 months (51.4-81.6mo) for GM and 37.4 months (31.3-42mo) for NGM (hazard ratio [HR] = 1.7; 95% CI = 1.3-2.2, P<0.001). In univariate OS analysis, age, delay between initial diagnosis and metastases, MSKCC, bone/lung metastases, and GM or NGM group were significant parameters (P<0.001). In multivariate analysis, adjusted according to MSKCC risk group, NGM vs. GM was a strong prognostic factor (HR = 1.4; 95% CI = 1.0-1.8, P=0.026); bone or liver metastases were also significant (HR = 1.3; 95% CI = 1.1-1.7, P<0.02; HR = 1.4; 95% CI = 1.1-1.7, P<0.02, respectively). Even in patients without bone or liver metastases, GM status was significant (HR = 1.8; 95% CI = 1.2-2.7, P<0.004).

Conclusions: This large retrospective study shows that the presence of at least 1 GM site in development of mccRCC was associated with a significantly longer OS. The presence of GMs vs. NGM disease was an independent prognostic factor for survival irrespective of the presence or absence of bone or liver metastases. This finding could affect daily practice in which patients with mccRCC and GMs should receive more aggressive treatment with a potential for long-term survival. The causal mechanisms for this improved prognosis in GM mccRCC would be evaluated in translational studies.

Keywords: Antiangiogenic therapy; Clear cell renal carcinoma; Glandular metastases; Kidney cancer; Prognosis factors; Survival outcome; Targeted therapies.