Lymphedema, characterized by disruptions to the flow of lymphatic fluid, commonly occurs in cancer survivors and has been linked to increased depression, anxiety, pain, and low health-related quality of life.1 Although there is no curative treatment, patients with lymphedema may receive outpatient care to help mitigate symptoms and reduce disease progression.2 Without proper management, lymphedema can progress to recurrent cellulitis and hospitalization. The objective of this cohort study was to identify factors associated with high costs during lymphedema-related hospitalizations.
We used the Healthcare Cost and Utilization Project National Inpatient Sample to identify lymphedema-related hospitalizations.3 All hospitalizations for lymphedema and lymphedema-associated cellulitis were included by identifying adult patients (≥18 years old) who were admitted between January 1, 2012, and December 31, 2017, with (1) a primary diagnosis of lymphedema or (2) a primary diagnosis of cellulitis with a secondary diagnosis of lymphedema. Hospitalizations were classified by disease site (upper vs lower extremity). Among patients admitted for cellulitis, codes specified the disease site; in patients admitted for lymphedema, codes specified the disease site as postmastectomy (upper extremity) or other (lower extremity). International Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes were used for site specification. Cost to charge ratios were used to estimate reimbursed hospitalization costs. This study was considered exempt by the University of North Carolina institutional review board because the database conforms to the definition of a limited data set and no informed consent is necessary for publicly available data sets. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
The statistical analysis was performed between January 4 and June 30, 2020. Multivariable logistic regression analysis was used to estimate the association between patient, disease, and hospital characteristics and extreme costs. Extreme costs were defined as those in the top 20th percentile of costs. Multivariable generalized gamma regression analysis was used to estimate the mean change in costs. Models were adjusted for disease site, age, sex, race/ethnicity, expected primary payer, median zip code income, Charlson Comorbidity Index score, hospital size, hospital location (urban, rural, or suburban) and teaching status, hospital region (Northeast, South, Midwest, or West), and year of admission. Analyses were conducted using SAS, version 9.4 software (SAS Institute Inc). Appropriate measures (sampling weights and survey-weighted regression) were used to account for the complex sample design and were weighted to obtain national estimates.4
An estimated 165 075 lymphedema-related hospitalizations occurred in the United States between January 1, 2012, and December 31, 2017. The mean (SD) patient age was 62.5 (15.0) years. Of the total hospitalizations, women represented 90 890 (59.3%) and men 62 225 (40.6%). In terms of racial demographic characteristics, 121 700 (79.4%) were non-Hispanic White patients, 18 230 (11.9%) were Black patients, 8575 (5.6%) were Hispanic patients, and 4610 (3.0%) were of non-Hispanic other races. Total reimbursed costs were $1 349 047 780, and the median reimbursed cost of hospitalization was $6180 (interquartile range [IQR], $4089-$9646). Extreme costs were hospitalization costs of $10 893 or higher.
Among 32 590 hospitalizations with extreme costs, 30 240 (92.8%) involved lower extremities, and 2350 (7.2%) occurred in patients with 3 or more comorbid conditions. After adjustment, lower extremity disease (odds ratio [OR], 1.75; 95% CI, 1.56-1.97), people of color (Black: OR, 1.16; 95% CI, 1.06-1.28; non-Hispanic other: OR, 1.44; 95% CI 1.23-1.68), younger age (eg, for patients aged 18-49 years: OR, 1.48; 95% CI, 1.32-1.67), and having at least 1 comorbid condition (eg, for patients with a Charlson Comorbidity Index score ≥3: OR, 2.25; 95% CI, 2.07-2.45) were associated with extreme costs (Figure 1). The expected primary payer, median zip code income, and hospital bed size had no impact. Costs among patients admitted with lower extremity disease were 27% higher compared with those with upper extremity disease (median [IQR] cost in thousands, $6429 [$4271-$9912] vs $4587 [$3054-$7350]; relative difference, 1.27; 95% CI, 1.22-1.32) (Figure 2). Patients with 3 or more comorbid conditions had 39% higher costs than patients with none (median [IQR] cost in thousands, $7184 [$4797-$11 2292] vs $5362 [$3550-$8410]; relative difference, 1.39; 95% CI, 1.35-1.43).
The findings of this analysis suggest factors that may be associated with greater median hospitalization costs and describe the characteristics of lymphedema hospitalizations that may involve extreme costs. We found that lymphedema-related hospitalizations between January 1, 2012, and December 31, 2017, resulted in more than $1 billion of reimbursed costs in the US health care system. This finding was in concordance with hospitalization costs from previous studies of lymphedema of the upper extremities after breast cancer treatment.5 However, compared with estimates from other high-income countries, the US costs were far higher.6
This study has several limitations. First, the Healthcare Cost and Utilization Project National Inpatient Sample uses discharge records, and hospitalizations for cellulitis when lymphedema was not recorded would have been excluded. We also assumed that admissions for “other” lymphedema were for lower extremity disease and that lymphedema occurring in patients with head and neck cancers or after lumpectomy would be miscategorized. However, a primary diagnosis of other lymphedema occurred in only 7% of hospitalizations, and we expect that misclassification and bias toward the null hypothesis were relatively minimal.
Outpatient lymphedema management programs, including physical therapy and surgical procedures for patients with multiple comorbid conditions, may improve lymphedema care and patient outcomes considerably and have the potential to result in substantial savings to the health care system.
Accepted for Publication: November 18, 2020.
Published Online: February 18, 2021. doi:10.1001/jamaoncol.2020.7891
Corresponding Author: Adeyemi A. Ogunleye, MD, Department of Surgery, UNC School of Medicine at Chapel Hill, Burnett-Womack Building, CB# 7195, Chapel Hill, NC 27599-7050 (email@example.com).
Author Contributions: Ms Roberson and Dr Strassle had full access to the data in the study and take full responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Strassle, Fasehun, Ogunleye.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Roberson, Strassle, Fasehun, Ogunleye.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Roberson, Strassle.
Administrative, technical, or material support: Strassle, Fasehun, Erim, Ogunleye.
Supervision: Strassle, Erim, Ogunleye.
Conflict of Interest Disclosures: None reported.
Meeting Presentation: This work was presented at the American College of Surgeons Clinical Congress 2020; October 4, 2020; Chicago, Illinois.