Factors Associated with Clinically Meaningful Pain Reduction Following Phase-I Complex Decongestive Therapy in Breast...

Background: Upper-limb lymphedema after breast cancer treatment is associated with pain, functional limitations, and impaired quality of life. Although complex decongestive therapy (CDT) is standard conservative care, prospective evidence regarding factors associated with clinically meaningful response remains limited. We evaluated the short-term outcomes following Phase-I CDT and identified factors associated with clinically meaningful pain reduction. Methods: A prospective observational study was conducted in 94 women with breast cancer-related lymphedema undergoing a standardized 14-day Phase-I CDT program. Outcomes included limb circumference, pain intensity measured using the Visual Analogue Scale (VAS), and quality of life assessed with LYMQOL-Arm. Clinically meaningful improvement was defined a priori as a reduction of at least 2 points on the VAS (ΔVAS ≥ 2). Analyses included paired t-tests, Cohen's d, multivariable logistic regression, analysis of covariance (ANCOVA), and receiver operating characteristic (ROC) analysis. Results: Significant reductions in limb circumference were observed across all measurement levels (3.08-5.83%; all p < 0.001). Pain intensity decreased from 5.53 ± 2.15 to 2.82 ± 1.41, with a mean reduction of 2.71 points (95% CI 2.32-3.11; p < 0.001) and a very large effect size (Cohen's d = 1.40). All LYMQOL domains improved significantly. Higher baseline pain intensity was associated with a greater likelihood of achieving the predefined criterion for clinically meaningful improvement (OR 3.03; 95% CI 1.91-4.80), while older age was associated with reduced odds of response (OR 0.90; 95% CI 0.85-0.96). Baseline pain intensity demonstrated good discriminative performance (AUC 0.85). Circumference changes were not correlated with subjective improvement. Conclusions: Following the 14-day Phase-I CDT program, statistically significant reductions in total limb circumference, clinically meaningful pain reduction, and significant improvements in quality of life were observed. Exploratory analyses demonstrated an association between baseline pain intensity and the predefined responder outcome; however, this association is structurally influenced by the mathematical relationship between baseline VAS and the responder definition, baseline-dependent opportunity for improvement, and regression to the mean. Therefore, it should not be interpreted as evidence of an independent predictive effect and requires external validation before being considered for patient stratification or clinical decision-making. Because of the observational pre-post design without a control group, the observed changes cannot be attributed specifically to Phase-I CDT.