Prevalence and Prognostic Significance of Hyponatremia in Lung Cancer Patients: Systematic Review and Meta-Analysis

Abstract Background The prevalence of hyponatremia is highly variable among lung cancer patients. It is also an important predictive factor, according to numerous studies. However, its prevalence and prognostic significance in subgroups of lung cancer patients, e.g. in small cell and non-small cell lung cancers (SCLC and NSCLC, respectively), have not yet been evaluated in a meta-analysis.Methods We report this systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2009) Statement. We have registered our meta-analysis and review’s protocol to the PROSPERO International Prospective Register of Systematic Reviews, with the following registration number: CRD42020167013. A systematic search was done in the following sources: MEDLINE, Embase, CENTRAL, Web of Science, ClinicalTrials.gov, a WHO Global Health Library. We extracted the effect measure for each outcome as the relative risk (RR) with the related 95% confidence interval (CI). Results We identified a total of 8127 potentially eligible studies and we included 25 studies in our evaluation. The prevalence of hyponatremia in lung cancer patients varied between 3% and 56.1% with an average of 23% without any significant differences between the following subgroups: cancer type (p=0.780), gender (p=0.223), age (p=0.773), ECOG state (p=0.317) and the extent of disease (p=0.999). Hyponatremia was more consistently an independent prognostic factor in NSCLC than in SCLC. The overall survival (OS) was significantly lower in hyponatremic compared to normonatremic patients at 10 months (RR: 0.59, 95% CI, 0.47 to 0.74, p<0.001) and at 20 months (RR: 0.44, 95% CI, 0.33 to 0.59, p<0.001), with worse survival rates in NSCLC than in SCLC (27% vs 42%) (p<0.001). If hyponatremia was corrected, OS at 10 months was 1.83 times higher than in the uncorrected hyponatremia group (95% CI, 1.37 to 2.44, p<0.001), but at 20 months no statistically significant difference could be found between these subgroups (p=0.067).Conclusions Low serum sodium levels have a negative impact on mortality at 10 and 20 months, which is more pronounced among NSCLC patients. The correction of hyponatremia has a positive effect on OS rates at 10 months, but this advantage disappears by 20 months.