Preoperative Serum Sodium Level as a Prognostic and Predictive Biomarker for Adjuvant Therapy in Esophageal Cancer

BACKGROUND: Low serum sodium has been associated with unfavorable outcome in several cancers. The prognostic value of serum sodium in esophageal carcinoma (EC) remains unclear. This study aimed to investigate preoperative serum sodium in association with outcome and survival benefit of adjuvant therapy for patients with EC. METHODS: Preoperative serum sodium and clinicopathological indexes were retrospectively analyzed in 2155 patients who underwent esophagectomy at Sichuan cancer hospital. Overall survival (OS) and disease-free survival (DFS) were analyzed by using Kaplan-Meier method and Cox regression. Benefit of adjuvant therapy was estimated by using Propensity Score Matching. RESULTS: The incidence of hyponatremia and hypernatremia were 2% (43/2155) and 3.5% (76/2155) in treatment-naive patients. Both sodium disorders indicated unfavorable OS (hyponatremia, adjusted HR[95% CI] = 1.78[1.2–2.62]; hypernatremia, adjusted HR = 1.52[1.1–2.11]) and DFS (hyponatremia, adjusted HR[95% CI] = 1.52[1.03–2.23]; hypernatremia, adjusted HR = 1.45[1.06–1.99]). Decreased sodium concentrations within the normal range were associated with poor OS and DFS. Postoperative adjuvant therapy was associated with improved three-year OS (56.6 vs. 40%; adjusted HR = 0.55 [95% CI, 0.41–0.73]) and DFS (51.9 vs. 36.2%; adjusted HR = 0.63 [95% CI, 0.48–0.83]) versus surgery alone in patients with low serum sodium (Na < 139.6 mmol/liter), but not in other sodium subgroups. Meanwhile, serum sodium was inversely correlated with cell counts of leukocytes, neutrophils, monocytes and C-reactive protein levels. CONCLUSIONS: These results suggested that low preoperative serum sodium is associated with poor outcome in EC patients, and may predict survival benefit of adjuvant therapy.