AbstractBackgroundPrevalence and risk of poor psychological outcomes following rhabdomyosarcoma (RMS) are not well‐established.MethodsParticipants in this cross‐sectional, case‐control study (n = 713 survivors, 42.5% female; mean [SD] age, 30.5 [6.6] years; n = 706 siblings, 57.2% female; mean age, 32.8,[7.9] years) completed measures of neurocognition, emotional distress, and health‐related quality of life (HRQOL). Multivariable logistic regression models identified treatments, health behaviors, and chronic conditions associated with impairment.ResultsRelative to siblings, more survivors reported neurocognitive impairment (task efficiency: 21.1% vs. 13.7%, emotional regulation: 16.7% vs. 11.0%, memory: 19.3% vs. 15.1%), elevated emotional distress (somatic distress: 12.9% vs. 4.7%, anxiety: 11.7% vs. 5.9%, depression: 22.8% vs. 16.9%) and poorer HRQOL (physical functioning: 11.1% vs. 2.8%, role functioning due to physical problems: 16.8% vs. 8.2%, pain: 17.5% vs. 10.0%, vitality: 22.3% vs. 13.8%, social functioning: 14.4% vs. 6.8%, emotional functioning: 17.1% vs. 10.6%). Cranial radiation increased risk for impaired task efficiency (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.14–4.63), whereas chest and pelvic radiation predicted increased risk of physical functioning (OR, 2.68; 95% CI, 1.16–6.21 and OR, 3.44; 95% CI, 1.70–6.95, respectively). Smoking was associated with impaired task efficiency (OR, 2.06; 95% CI, 1.14–3.70), memory (OR, 2.23; 95% CI, 1.26–3.95), anxiety (OR, 2.71; 95% CI, 1.36–5.41) and depression (OR, 1.77; 95% CI, 1.01–3.11). Neurologic conditions increased risk of anxiety (OR, 2.30; 95% CI, 1.04–5.10), and hearing conditions increased risk of depression (OR, 1.79; 95% CI, 1.05–3.03). Neurologic and hearing conditions, respectively, were associated with impaired memory (OR, 2.44; 95% CI, 1.20–4.95 and OR, 1.87; 95% CI, 1.05–3.35) and poor health perception (OR, 2.62; 95% CI, 1.62–1.28 and OR, 2.33; 95% CI, 1.34–4.06).ConclusionsRMS survivors are at significant risk for poor psychological outcomes. Advancing therapies for local control, smoking cessation, and managing chronic medical conditions may mitigate poor outcomes following RMS.