Abstract
BACKGROUND: Breast cancer-related lymphoedema (BCRL) affects one in six breast cancer survivors and causes significant morbidity. Compression therapy is a cornerstone of BCRL treatment, yet response varies considerably and predictors of efficacy are not well-characterised, often conflicting across studies. Accordingly, this study aimed to identify and synthesise predictive factors for compression treatment response in BCRL. METHODS: In this systematic review and meta-analysis, Medline ALL, Embase, Scopus, Web of Science, and Cochrane controlled trials and systematic review databases were systematically searched from inception to Dec 9, 2025. Eligible studies included all study designs, across any setting or timepoint, that evaluated compression treatment response predictors for BCRL. Studies comparing treatment modalities without evaluation of predictive factors on response were excluded. For each study, two independent reviewers conducted screening, data extraction, and bias/uncertainty assessments (QUIPS, GRADE). The primary outcome was percentage reduction in excess volume (PREV). Findings were integrated using narrative synthesis and random-effects meta-analysis, with subgroup analyses based on study characteristics. This review was registered with PROSPERO, CRD42025633750. FINDINGS: Across 3247 studies, 67 met eligibility criteria (N = 6401). Mean PREV across 39 studies and 4529 patients was 45·13% (SD: 59·27; 95% CI: 43·41-46·86). Study quality was moderate, with 78·95% (45/57) articles having low bias in ≥3/6 QUIPS domains. Moderate-certainty evidence supported high baseline excess volume (n = 12 studies), severe lymphoedema (n = 9), prior arm infection (n = 4), or prior lymphoedema therapy (n = 3) as predictors of lower PREV, and increased treatment compliance (n = 6) or lymphoscintigraphic uptake (n = 4) for higher PREV. Meta-analysis of nine studies revealed significant associations between lower PREV and older age (r = -0·135; 95% CI: -0·239, -0·028; p = 0·013; moderate certainty; I(2) = 30·78), higher baseline excess volume (r = -0·276; 95% CI: -0·453, -0·079; p = 0·0067; moderate certainty; I(2) = 86·87), and longer lymphoedema duration (r = -0·229; 95% CI: -0·361, -0·087; p = 0·0018; high certainty; I(2) = 10·38). Heterogeneity was low except for baseline volume, with minimal publication bias. Qualitative synthesis identified heterogeneity in age and lymphoedema duration categorisation, BCRL criteria, treatment protocols, and outcome measures. INTERPRETATION: This synthesis of 71 distinct factors identified multiple predictors of compression response with moderate supportive evidence. Our findings support early intervention and adherence strategies in BCRL and provide an evidence base to enhance treatment decisions, patient counselling, and predictive model development. However, variability in study characteristics and analysis methodologies constrained comparability across predictors, limiting precision and consistency in low-certainty factors, like body-mass index or postoperative duration before lymphoedema onset, that may require further evidence before clinical application. FUNDING: None.