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

Abstract

Background: The prevalence of hyponatremia is highly variable among patients with lung cancer. However, its prevalence and prognostic significance in subgroups of patients with lung cancer have not yet been evaluated in a meta-analysis.Methods: We have registered our meta-analysis and review 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.Results: We identified a total of 8,962 potentially eligible studies, and we included 31 articles in our evaluation. The prevalence of hyponatremia in patients with lung cancer varied between 3 and 94.8% with an average of 25% without any significant differences between the following subgroups: histotype, gender, age, Eastern Cooperative Oncology Group (ECOG) state, and the extent of disease. The overall survival (OS) was significantly lower in hyponatremic compared to normonatremic patients at 10 months [RR.59 (95% CI.47–0.74), p < 0.001] and at 20 months [RR.44 (95% CI.33–0.59), p < 0.001], with worse survival rates in non-small cell lung cancer (NSCLC) [RR.27 (95% CI.12–0.44), p < 0.001] than in small cell lung cancer (SCLC) [RR.42 (95% CI.27–0.57), p < 0.001]. If hyponatremia was corrected, OS at 10 months was significantly higher than in the uncorrected hyponatremia group [RR 1.83 (95% CI 1.37–2.44), p < 0.001], but, at 20 months, no statistically significant difference could be found between these subgroups [RR 2.65 (95% CI.94–7.50), p = 0.067].Conclusions: Patients with lung cancer diagnosed with hyponatremia, especially patients with NSCLC, seem to have significantly lower survival rates than normonatremic patients. If hyponatremia remains uncorrected, the mortality rates might be even higher.

Hyponatraemia and the syndrome of inappropriate antidiuresis (SIAD) in cancer

“…There is a considerable accumulation of evidence to show that in hospitalised patients with cancer, all-cause hyponatraemia is associated with increased mortality, prolonged duration of in-patient stay and amplification of health care costs ( Hansen et al 2010 , Jeppesen et al 2010 , Petereit et al 2011 , Doshi et al 2012 , Abu Zeinah et al 2014 , Schutz et al 2014 , Berardi et al 2015 a , b ). Hyponatraemia has been associated with lower performance status using the Eastern Cooperative Group Performance Status (ECOG-PS) in patients with non-small cell lung cancer ( Chan et al 2020 ) and has been associated in two meta-analyses, with shorter overall survival in non-small cell lung cancer ( Sandfeld-Paulsen et al 2021 ) and all-cause lung cancer ( Bartalis et al 2021 ). It is important to emphasise that these are associations with hyponatraemia.…”

“…As long-term survivorship from cancer continues to improve, the deleterious effects of untreated chronic hyponatraemia on bone mineral density should also be considered ( Upala & Sanguankeo 2016 ). Treatment of SIAD to improve hyponatraemia in lung cancer has also been shown to improve overall survival at 10 but not 20 months, in a meta-analysis, though it should be acknowledged that longer follow-up will document diminishing returns on survival with a malignant process ( Bartalis et al 2021 ). The reason for the positive effect of active treatment of SIAD is not known.…”

“…The evidence is compelling that hyponatraemia is common in malignancy and has negative effects on performance, survival and duration of hospital stay. There are little data from randomised, prospective trials that treatment of hyponatraemia improves outcomes, but there is enough evidence from the data available to strongly suggest symptomatic ( Petereit et al 2013 , Bilgetekin et al 2021 , Ren & Yang 2021 ) and survival benefit ( Tiseo et al 2014 , Yang et al 2017 , Wu et al 2020 , Bartalis et al 2021 , Sandfeld-Paulsen et al 2021 ). Unpublished data from our own hospital (Murphy B., unpublished audit) suggest that other than renal medicine, where hyponatraemia is actively within-house, the lowest rate of endocrine referral is from patients who develop hyponatraemia on oncology/haematology services.…”

“…Since then, hyponatraemia has been described in a wide variety of malignant processes. The association has been documented most often and most comprehensively in bronchogenic carcinoma ( Alamoudi 2010 , Hansen et al 2010 , Castillo et al 2012 , Sengupta et al 2013 , Tiseo et al 2014 , Fiordoliva et al 2017 , Chan et al 2020 , Bartalis et al 2021 , Sandfeld-Paulsen et al 2021 ). A meta-analysis published in 2021, of 31 articles, showed the mean prevalence of hyponatraemia in lung cancer was 25%; however, the findings were highly discordant, ranging from 3 to 95% due to heterogeneity in patient characteristics, evaluation of hyponatraemia and the cut-off points used ( Bartalis et al 2021 ).…”

“…The association has been documented most often and most comprehensively in bronchogenic carcinoma ( Alamoudi 2010 , Hansen et al 2010 , Castillo et al 2012 , Sengupta et al 2013 , Tiseo et al 2014 , Fiordoliva et al 2017 , Chan et al 2020 , Bartalis et al 2021 , Sandfeld-Paulsen et al 2021 ). A meta-analysis published in 2021, of 31 articles, showed the mean prevalence of hyponatraemia in lung cancer was 25%; however, the findings were highly discordant, ranging from 3 to 95% due to heterogeneity in patient characteristics, evaluation of hyponatraemia and the cut-off points used ( Bartalis et al 2021 ). Although no study has compared the incidence of SIAD in lung cancer by histological type, it is widely accepted that SIAD due to ectopic production of vasopressin is significantly more common in small cell lung cancer than non-small cell ( Cuesta & Thompson 2016 ).…”