| Summary: | Abstract Background Mistletoe extracts are used as an adjunct therapy for cancer patients, but there is dissent as to whether this therapy has a positive impact on quality of life (QoL). Methods We conducted a systematic review searching in several databases (Medline, Embase, CENTRAL, CINAHL, PsycInfo, Science Citation Index, clinicaltrials.gov, opengrey.org ) by combining terms that cover the fields of “neoplasm”, “quality of life” and “mistletoe”. We included prospective controlled trials that compared mistletoe extracts with a control in cancer patients and reported QoL or related dimensions. The quality of the studies was assessed with the Cochrane Risk of Bias tool version 2. We conducted a quantitative meta-analysis. Results We included 26 publications with 30 data sets. The studies were heterogeneous. The pooled standardized mean difference (random effects model) for global QoL after treatment with mistletoe extracts vs. control was d = 0.61 (95% CI 0.41–0.81, p < 0,00001). The effect was stronger for younger patients, with longer treatment, in studies with lower risk of bias, in randomized and blinded studies. Sensitivity analyses support the validity of the finding. 50% of the QoL subdomains (e.g. pain, nausea) show a significant improvement after mistletoe treatment. Most studies have a high risk of bias or at least raise some concern. Conclusion Mistletoe extracts produce a significant, medium-sized effect on QoL in cancer. Risk of bias in the analyzed studies is likely due to the specific type of treatment, which is difficult to blind; yet this risk is unlikely to affect the outcome. PROSPERO registration CRD42019137704 .
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