Predicting cancer-related lymphedema following axillary surgery: a decade of outcomes from a tertiary cancer center

Background: No clinically applicable method currently exists to predict which patients will develop cancer-related lymphedema following axillary surgery or when it will occur. This study aimed to identify predictive factors for lymphedema and develop a clinically applicable algorithm to estimate both individualized risk and time to onset. Methods: We conducted a retrospective cohort study of 15 666 female patients who underwent axillary surgery at a tertiary cancer center between 2013 and 2024. Demographic, clinical, and laboratory data were collected, and patients were followed for the development of lymphedema. Two multivariable models were constructed: a logistic regression model to predict lymphedema risk and a linear regression model to estimate time to first diagnosis. Results: In the clinical prediction model, significant predictors included chemotherapy (OR = 2.445, 95% CI: 2.189–2.734, P < 0.0001), radiation (OR = 1.960, 95% CI: 1.777–2.162, P < 0.0001), Black race (OR = 1.443, 95% CI: 1.248–1.666, P < 0.0001), BMI > 30 (OR = 1.385, 95% CI: 1.255–1.528, P < 0.0001), and diabetes (OR = 1.168, 95% CI: 1.040–1.312, P = 0.0085). Predictors of rapid onset included radiation (β = –4.496, 95% CI: –6.376 to –2.617, P < 0.0001), Black race (β = –4.159, 95% CI: –6.876 to –1.442, P = 0.0027), and Asian race (β = –6.796, 95% CI: –12.76 to –0.830, P = 0.0256). Diabetes was associated with delayed lymphedema onset (β = 2.813, 95% CI: 0.619–5.008, P = 0.0120). Hemoglobin A1c at the time of axillary surgery was independently associated with increased risk (OR = 1.114, 95% CI: 1.001–1.237, P = 0.0447) and later onset (β = 3.708, 95% CI: 1.244–6.171, P = 0.0035). Conclusion: This is the largest study to develop clinically applicable prediction models for both individualized risk and timing of lymphedema following axillary surgery. Our findings confirm known risk factors and demonstrate that not only diabetes but also the severity of glycemic control influences lymphedema risk and onset. HbA1c emerges as a novel and modifiable marker, underscoring the role of metabolic dysregulation in disease presentation.