Associations of obesity and visceral adiposity with overall survival and immune-related adverse events in patients with endometrial cancer treated with immunotherapy: a retrospective analysis
Abstract
BackgroundEndometrial cancer is a common gynecological malignancy with a rising global burden and a close association with obesity and metabolic dysfunction. Immune checkpoint inhibitors (ICIs) are now used in advanced or recurrent endometrial cancer, but the relationship between obesity, body composition, survival, and immune-related adverse events (irAEs) remains uncertain. This study evaluated the associations of BMI category and CT-derived adiposity measures with overall survival and irAEs in women with endometrial cancer treated with immunotherapy. Direct efficacy endpoints, including objective response rate and progression-free survival, were not assessed.MethodsWe performed a single-center retrospective cohort study of 338 patients with histologically confirmed endometrial cancer who received at least one dose of ICI therapy between January 2020 and March 2025. Primary BMI classification used the WHO Expert Consultation Asian public-health action points: normal 18.5-22.9 kg/m², overweight 23.0-27.4 kg/m², and obesity-risk ≥27.5 kg/m². These were analytic risk categories rather than diagnostic obesity classes. Conventional WHO categories were used only for descriptive reclassification. A directed acyclic graph (DAG) identified the conceptual confounder set before model fitting. BMI, VAT, and SAT were evaluated in separate DAG-guided total-effect models. Prespecified sensitivity analyses assessed selected survival and safety models by treatment-record documentation completeness and ICI treatment line; expanded interaction analyses evaluated record-completeness modification across adiposity-outcome models. Treatment-record completeness was used only to assess potential bias from incomplete capture of treatment exposure; it was not interpreted as ICI treatment completion.ResultsAsian-specific BMI classification yielded 58 normal-BMI, 119 overweight, and 161 obesity-risk patients. Complete treatment-record documentation was available for 214 (63.3%) patients. In record-completeness survival analyses, the VAT-mortality association was HR 1.12 per 10 cm² (95% CI 1.03-1.22; p=0.008) in the complete-record subset and was directionally similar but less precise in the incomplete-record subset (HR 1.08, 95% CI 0.96-1.22; p=0.20). Forty-six patients in the obesity-risk category received first-line ICI therapy. Adjusted BMI-by-treatment-line survival analyses showed no statistically significant interaction (p for interaction=0.68), although subgroup confidence intervals were wide. In separate DAG-guided models, VAT was associated with mortality (HR 1.11 per 10 cm², 95% CI 1.03-1.20; p=0.006), whereas BMI category and SAT were not independently associated with overall survival. Any irAE occurred in 18/58 (31.0%), 60/119 (50.4%), and 86/161 (53.4%) patients across normal, overweight, and obesity-risk categories, respectively (p=0.012). VAT, but not SAT, was associated with time to first documented irAE.ConclusionIn this retrospective ICI-treated endometrial cancer cohort, CT-derived VAT, but not BMI category or SAT, was independently associated with overall survival and earlier first documented irAE in DAG-guided models. Record-completeness and treatment-line sensitivity analyses improved assessment of potential exposure-related bias but did not establish ICI treatment completion or eliminate residual confounding. Findings remain hypothesis-generating because of treatment heterogeneity, imprecise subgroup estimates, and incomplete real-world exposure data.
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BibTeX
@article{wei2026associations,
title = {{Associations of obesity and visceral adiposity with overall survival and immune-related adverse events in patients with endometrial cancer treated with immunotherapy: a retrospective analysis}},
author = {Xing Wei and Xianping Yuan and Qing Zeng and Shichun Shen and Zhen Wang},
journal = {Frontiers in Oncology},
year = {2026},
month = nov,
doi = {10.3389/fonc.2026.1866263},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1866263},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Associations of obesity and visceral adiposity with overall survival and immune-related adverse events in patients with endometrial cancer treated with immunotherapy: a retrospective analysis
AU - Xing Wei
AU - Xianping Yuan
AU - Qing Zeng
AU - Shichun Shen
AU - Zhen Wang
PY - 2026
DA - 2026/11/09
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1866263
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1866263
AB - BackgroundEndometrial cancer is a common gynecological malignancy with a rising global burden and a close association with obesity and metabolic dysfunction. Immune checkpoint inhibitors (ICIs) are now used in advanced or recurrent endometrial cancer, but the relationship between obesity, body composition, survival, and immune-related adverse events (irAEs) remains uncertain. This study evaluated the associations of BMI category and CT-derived adiposity measures with overall survival and irAEs in women with endometrial cancer treated with immunotherapy. Direct efficacy endpoints, including objective response rate and progression-free survival, were not assessed.MethodsWe performed a single-center retrospective cohort study of 338 patients with histologically confirmed endometrial cancer who received at least one dose of ICI therapy between January 2020 and March 2025. Primary BMI classification used the WHO Expert Consultation Asian public-health action points: normal 18.5-22.9 kg/m², overweight 23.0-27.4 kg/m², and obesity-risk ≥27.5 kg/m². These were analytic risk categories rather than diagnostic obesity classes. Conventional WHO categories were used only for descriptive reclassification. A directed acyclic graph (DAG) identified the conceptual confounder set before model fitting. BMI, VAT, and SAT were evaluated in separate DAG-guided total-effect models. Prespecified sensitivity analyses assessed selected survival and safety models by treatment-record documentation completeness and ICI treatment line; expanded interaction analyses evaluated record-completeness modification across adiposity-outcome models. Treatment-record completeness was used only to assess potential bias from incomplete capture of treatment exposure; it was not interpreted as ICI treatment completion.ResultsAsian-specific BMI classification yielded 58 normal-BMI, 119 overweight, and 161 obesity-risk patients. Complete treatment-record documentation was available for 214 (63.3%) patients. In record-completeness survival analyses, the VAT-mortality association was HR 1.12 per 10 cm² (95% CI 1.03-1.22; p=0.008) in the complete-record subset and was directionally similar but less precise in the incomplete-record subset (HR 1.08, 95% CI 0.96-1.22; p=0.20). Forty-six patients in the obesity-risk category received first-line ICI therapy. Adjusted BMI-by-treatment-line survival analyses showed no statistically significant interaction (p for interaction=0.68), although subgroup confidence intervals were wide. In separate DAG-guided models, VAT was associated with mortality (HR 1.11 per 10 cm², 95% CI 1.03-1.20; p=0.006), whereas BMI category and SAT were not independently associated with overall survival. Any irAE occurred in 18/58 (31.0%), 60/119 (50.4%), and 86/161 (53.4%) patients across normal, overweight, and obesity-risk categories, respectively (p=0.012). VAT, but not SAT, was associated with time to first documented irAE.ConclusionIn this retrospective ICI-treated endometrial cancer cohort, CT-derived VAT, but not BMI category or SAT, was independently associated with overall survival and earlier first documented irAE in DAG-guided models. Record-completeness and treatment-line sensitivity analyses improved assessment of potential exposure-related bias but did not establish ICI treatment completion or eliminate residual confounding. Findings remain hypothesis-generating because of treatment heterogeneity, imprecise subgroup estimates, and incomplete real-world exposure data.
SN - 2234-943X
ER -