BACKGROUND: Conduct a systematic review of previous systematic reviews with meta-analysis to determine the effects of exercise (aerobic, strength or both) on cancer-related-fatigue (CRF) in adults with any type of cancer. METHODS: Systematic reviews with meta-analyses of previous randomized controlled trials published through July of 2016 were included by searching six electronic databases and cross-referencing. Dual-selection and data abstraction were conducted. Methodological quality was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) instrument. Standardized mean differences (SMD) that were pooled using random-effects models were included as the effect size. In addition, 95% prediction intervals (PI), number needed-to-treat (NNT) and percentile improvements were calculated. RESULTS: Sixteen studies representing 2 to 48 SMD effect sizes per analysis (mean +/- SD 7 +/- 8, median 5) and 37 to 3,254 participants (mean +/- SD 633 +/- 690, median 400) were included. Length of training lasted from 3 to 52 weeks (mean +/- SD 14.6 +/- 3.1, median 14), frequency from 1 to 10 times per week (mean +/- SD 3.4 +/- 0.8, median 3), and duration from 10 to 120 min per session (mean +/- SD 44.3 +/- 5.5, median 45). Adjusted AMSTAR scores ranged from 44.4% to 80.0% (mean +/- SD 68.8% +/- 12.0%, median 72.5%). Overall, mean SMD improvements in CRF ranged from -1.05 to -0.01, with 22 of 55 meta-analytic results (52.7%) statistically significant (non-overlapping 95% CI). When PI were calculated for results with non-overlapping 95% CI, only 3 of 25 (12%) yielded non-overlapping 95% PI favoring reductions in CRF. Number needed-to-treat and percentile improvements ranged from 3 to 16 and 4.4 to 26.4, respectively. CONCLUSIONS: A lack of certainty exists regarding the benefits of exercise on CRF in adults. However, exercise does not appear to increase CRF in adults. TRIAL REGISTRATION: PROSPERO registration number CRD42016045405.

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