Comparative effectiveness of non-surgical interventions and their combinations for the prevention of breast cancer-related lymphedema: a systematic review and Bayesian network meta-analysis

Objective The aims of this study were to compare the relative effectiveness of non-surgical preventive interventions and their combinations on breast cancer-related lymphedema (BCRL) incidence and shoulder abduction range of motion (ROM) using Bayesian network meta-analysis (NMA) and to assess the certainty of evidence using the Confidence in Network Meta-Analysis (CINeMA) framework. Methods Eight databases (PubMed, Embase, Web of Science, Cochrane Library, CNKI, WanFang, VIP, and SinoMed) were searched through January 2026. Randomized controlled trials (RCTs) of non-surgical interventions for BCRL prevention in post-surgical breast cancer patients were included. The primary outcome was BCRL incidence, which was analyzed using a Bayesian random-effects NMA with arm-level binomial likelihood and log link (risk ratio). The primary analysis was restricted to studies with a follow-up of at least 6 months, based on evidence that the risk of BCRL in axillary lymph node dissection populations peaks at 6–12 months postoperatively. A meta-regression with follow-up duration as a covariate was conducted on the full 45-study network to validate this restriction. Shoulder abduction ROM was analyzed as a secondary outcome after data cleaning to ensure measurement homogeneity. Results A total of 100 RCTs were included in the qualitative synthesis. The primary BCRL analysis comprised 27 studies (57 arms, 4,660 participants, 11 nodes). Seven interventions showed credible intervals excluding 1: compression therapy combined with resistance training (COMP+RT) [risk ratio (RR) = 0.146, 95% credible interval (95%CrI) = 0.057–0.366, surface under the cumulative ranking curve (SUCRA) = 85.1%], RT with supervised exercise (RT+SUP-EX) (RR = 0.147, 95%CrI = 0.019–0.665, SUCRA = 80.8%), COMP with manual lymphatic drainage (COMP+MLD) (RR = 0.121, 95%CrI = 0.004–0.915, SUCRA = 80.6%), intermittent pneumatic compression with MLD (IPC+MLD) (RR = 0.255, 95%CrI = 0.153–0.397, SUCRA = 69.3%), microwave therapy (MW) (RR = 0.313, 95%CrI = 0.090–0.926, SUCRA = 57.8%), IPC (RR = 0.396, 95%CrI = 0.197–0.765, SUCRA = 47.8%), and MLD (RR = 0.467, 95%CrI = 0.320–0.650, SUCRA = 39.2%). COMP+RT ranked first in three of six analytical approaches. However, it was excluded as a sparse node under stricter diagnostic definitions. The meta-regression coefficient for follow-up duration was statistically significant ( β = 0.077/month, 95%CrI = 0.026–0.128), confirming that the treatment effects attenuated with longer follow-up. The cleaned ROM analysis (12 studies, 1,079 participants, 11 nodes) identified eight interventions with credible intervals excluding zero, led by acupoint massage with isokinetic strength training (AM+ISO) [mean difference (MD) = 22.83°, 95%CrI = 11.06–34.89, SUCRA = 85.2%]. Two interventions ranked in the top four for both outcomes: COMP+RT (BCRL rank 1 and ROM rank 4) and IPC+MLD (BCRL rank 4 and ROM rank 3). Conclusion COMP+RT demonstrated the most robust evidence profile among all evaluated interventions, ranking first for BCRL incidence in three of six analytical approaches and in the top four for shoulder ROM. However, its evidence base was concentrated among studies using author-defined diagnostic criteria; under stricter diagnostic definitions, COMP+RT was excluded as a sparse node. These findings should be interpreted in the context of a predominantly low certainty evidence. Confirmatory trials with standardized diagnostic criteria and follow-up of at least 12 months are needed. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261279759.