Hyponatremia predicts immunotherapy resistance in biliary tract cancer

Hyponatremia, a common electrolyte imbalance in cancer patients, has frequently been disregarded in terms of its prognostic implications for immunotherapy. This study examined the prognostic implications of pre-treatment hyponatremia in patients with biliary tract cancers (BTC) undergoing immunotherapy. We retrospectively included 112 BTC patients who received immune checkpoint inhibitors (ICIs) treatment from August 2016 to December 2024, with an average follow-up period of 11.25 months. In accordance with the diagnosis of hyponatremia before the first ICIs treatment, patients were divided into two distinct groups. There were no significant differences in age (OR = 0.6, 95% CI, 0.2-1.8) or gender distribution (OR = 0.8, 95% CI, 0.3-2.4). Kaplan-Meier curves and the Mantel-Haenszel log-rank test were utilized to compare progression-free survival (PFS) and overall survival (OS) among groups. Cox and logistic regressions were employed to analyze the relationship between serum sodium levels and prognosis in 112 BTC patients, considering baseline characteristics. Patients with hyponatremia demonstrated reduced PFS (6 vs. 9 months, p < .001) and OS (7.5 vs. 11.3 months, p < .001*). Serum sodium was identified as an independent prognostic indicator for both PFS (HR = 4.5, 95% CI, 1.5-14.0) and OS (HR = 3.1, 95% CI, 1.2-8.3). Subgroup analysis indicated that BTC patients with hyponatremia experienced no advantage from immunotherapy regarding PFS and OS. Hyponatremia indicates unfavorable prognostic outcomes in BTC patients undergoing ICI treatment and may function as a significant prognostic biomarker.