Hyponatremia associates with poor outcome in metastatic renal cell carcinoma patients treated with everolimus: prognostic impact

Background: The prognostication of metastatic renal cell carcinoma (mRCC) is based on Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classifications. Research has shown that hyponatremia is associated with worse prognosis in cancer. We analyzed the association of hyponatremia and outcome in everolimus-treated mRCC patients.

Patients and methods: Baseline and on-treatment (≤12 weeks) sodium in 233 mRCC patients was analyzed using Kaplan–Meier, Cox regression and logistic regression. Baseline sodium was correlated with baseline thrombocyte and neutrophil values.

Results: 65 (28%) and 41 (18%) patients had sodium < lower limit of normal (LLN) at baseline and on-treatment, respectively. Baseline sodium < LLN was associated with shorter overall survival (OS) (6.1 vs. 10.3 months; p < .001) and progression-free survival (PFS) (2.8 vs. 3.5 months; p = .04). On-treatment sodium < LLN was associated with shorter OS (5.4 vs. 9.9 months; p < .001) and PFS (2.8 vs. 4.0 months; p < .001). In multivariate analyses adjusted for IMDC factors, baseline and on-treatment sodium < LLN were significantly associated with shorter OS (adjusted HR 1.46 (95% CI 1.04–2.05); p = .02; adjusted HR 1.80 (95% CI 1.23–2.61); p = .002; respectively). On-treatment sodium < LLN was significantly associated with progressive disease (OR 0.23 (95% CI 0.10–0.56); p = .001). A landmark analysis demonstrated that on-treatment hyponatremia was significantly associated with shorter OS and PFS (p = .01 and p = .03, respectively). On-treatment normalization of hyponatremia was associated with improved OS (unadjusted HR 0.61 (95% CI 0.35–0.98); p = .04), as compared to patients with sustained hyponatremia throughout follow-up.

Conclusions: Hyponatremia associates with poor outcome in mRCC patients treated with everolimus. On-treatment normalization of hyponatremia to normal sodium values associates with favorable outcome.