Rising mortality from malignant pleural Effusion in the United States, 1999-2020: Population-level trends and disparities

Malignant pleural effusion (MPE) indicates extensive tumor involvement of the pleural space and often reflects aggressive disease characteristics and advanced cancer progression. Despite its clinical and prognostic importance across multiple solid tumors, national mortality patterns attributable to MPE remain poorly characterized. We performed a population-based analysis to define demographic and temporal trends in MPE-related deaths in the United States.Methods: Using CDC WONDER Multiple Cause-of-Death data (1999-2020), we identified U.S. deaths listing MPE (ICD-10 C78.2) as a contributing cause. Age-adjusted mortality rates (AAMR; per 100,000; 2000 U.S. standard population) were calculated overall and by sex, race, ethnicity, age, region, and urbanization level. Temporal trends were assessed with Joinpoint regression using log-linear modeling and Weighted BIC for model selection. Annual percent change (APC) estimates and 95% confidence intervals were reported for each segment.Results: A total of 68,700 MPE-related deaths occurred from 1999-2020. The national AAMR increased from 0.68 to 1.40 per 100,000. The optimal model identified two joinpoints (2001, 2007). A modest early increase (APC 1999-2001: +6.7%, 95% CI -2.9 to 15.4) was followed by a transient decline (2001-2007: -4.1%, -9.8 to 8.9). From 2007-2020, mortality rose significantly with an APC of +6.4% (95% CI 5.2-7.8; p<0.01). Females accounted for 58% of deaths; female AAMR rose from 0.68 to 1.44 per 100,000 with three trend segments (APC 1999-2001: +9.6%; 2001-2007: -4.2%; 2007-2020: +6.3%, p<0.01). Male AAMR increased from 0.66 to 1.33 per 100,000, with a single joinpoint at 2007 (APC 1999-2007: −3.1%; 2007-2020: +6.3%, both p<0.01). Most decedents were ≥65 years (70%). Across the study period, racial distribution included White (83%), Black (12%), and Asian/Pacific Islander (4%); 6% were Hispanic. Mortality rates were highest in medium and small metropolitan regions. 50% of all deaths occurred in hospitals, 28% at home, and 8% in hospice facilities. Conclusions: MPE-associated mortality in the U.S. has increased markedly over two decades, with a sustained rise after 2007. Persistent disparities by age, race, and urbanization highlight vulnerable populations and ongoing inequities in early cancer detection, access to systemic therapy, and palliative resources. These findings illustrate a growing burden of advanced malignant disease and support the need for earlier oncologic intervention, improved metastatic surveillance, and therapies that address both tumor control and pleural fluid accumulation. The escalation of MPE mortality further supports the development of disease-modifying interventions beyond conventional drainage-centered management.