AbstractBackgroundSymptom burden in adolescents and young adults (AYA) with cancer is poorly characterized but impacts quality of life.MethodsAll Ontario, Canada AYA aged 15–29 years at diagnosis between 2010 and 2018 were linked to population‐based healthcare databases, including to Edmonton Symptom Assessment System‐revised (ESAS) scores, an 11‐point scale routinely obtained at the time of cancer‐related outpatient visits and collected provincially. Multistate models estimated mean duration of symptom severity states [none (0) vs. mild (1 vs. 2 vs. 3) vs. moderate (4–6) vs. severe (7–10)], trajectories, and subsequent mortality risk. Variables associated with severe symptoms were also determined.ResultsIn total, 4296 AYA with ≥1 ESAS score within a year of diagnosis were included (median age 25 years). Prevalent moderate/severe symptoms included fatigue (59% of AYA) and anxiety (44%). Across symptom type, AYA reporting moderate symptoms were likelier to subsequently experience improvement versus worsening. Risk of death within 6 months increased with increasing symptom burden and was highest in AYA with severe dyspnea (9.0%), pain (8.0%), or drowsiness (7.5%). AYA in the poorest urban neighborhoods were more likely to experience severe symptoms than in the wealthiest areas, with twice the odds of reporting severe depression [adjusted odds ratio (OR) 1.95, 95th confidence interval (95% CI) 1.37–2.78], pain (OR: 1.94, 95% CI: 1.39–2.70), and dyspnea (OR: 1.96, 95% CI: 1.27–3.02).ConclusionsAYA with cancer experience substantial symptom burden. Risk of death increased with symptom severity. Interventions targeting cancer fatigue and anxiety, and targeting AYA in lower‐income neighborhoods, are likely to improve quality of life in this population.