Prevalence and risk of psychological distress, anxiety and depression in adolescent and young adult (AYA) cancer survivors: A systematic review and meta‐analysis

Abstract Background Adolescent and young adult (AYA) cancer survivors (CS) face unique psychosocial challenges, which may affect their mental health. However, there are inconsistencies in AYA definitions and varying prevalence data on psychological distress, anxiety, and depression. We aimed to synthesize published literature on prevalence, risk, longitudinal changes, and predictors for these outcomes and estimate pooled prevalences. Methods We searched for observational studies published in English before June 1 2022, in PubMed, PsycINFO, Scopus, and Web of Science. Two researchers extracted independently information on study characteristics, prevalence, and risk. The pooled prevalence (PP) of psychological distress, anxiety, and depression was estimated using random‐effects models. Geographical region, treatment status, and assessment instruments were considered in stratified meta‐analyses. Results Sixty‐eight studies were included in the systematic review and 57 in the meta‐analyses. We estimated an overall prevalence of 32% (n = 30; 4226/15,213 AYAs; 95% CI, 23%–42%; I 2 = 99%) for psychological distress, 29% for anxiety (n = 24; 2828/8751 AYAs; 95% CI, 23%–36%; I 2 = 98%), and 24% (n = 35; 3428/16,638 AYAs; 95% CI, 18%–31%; I 2 = 98%) for depression. The range of PP of psychological distress varied across geographical regions, treatment status, and assessment instruments. The PP of anxiety varied significantly across continents, while no variations were seen for depression. Studies found higher risks for psychological distress, anxiety, and depression in AYAs compared to older cancer survivors or cancer‐free peers. Conclusions Our research found that one in three AYA‐CS experience psychological distress or anxiety and one in four are affected by depression, highlighting the need for specialized psychological services for AYA‐CS in oncology settings and AYA‐focused interventions.

eTable 5. Main findings on prevalence of psychological distress, anxiety and depression in AYA cancer survivors, comparison with reference groups and predictors eTable 6. Main findings on risk of developing psychological distress, anxiety and depression in AYA cancer survivors (n=16) eTable 7. Main findings on trajectories of psychological distress, anxiety and depression among AYA cancer survivors (n=10) eFigure 1. Modified Newcastle-Ottawa scale for assessing the quality of longitudinal studies Note: A study was considered representative if participants were recruited through random sampling strategies, cancer registries and databases or from multiple clinics or hospitals. Regarding exposure assessment, studies were assigned two stars if the participants were identified through cancer registries, medical records and databases and one star if they self-reported their diagnosis. Studies were assigned one star if they used validated tools (e.g. screeners) to assess psychological distress, anxiety and depression and two stars if the AYAs were clinically diagnosed with any of the outcomes of interest based on the DSM criteria for mental disorders. If no non-exposed cohort was selected, it was identified as no comparability between cohorts in terms of the variables involved and the study got no stars. eFigure 2. Modified Newcastle-Ottawa scale for assessing the quality of crosssectional studies.
Note: A study was considered representative if participants were recruited through random sampling strategies, cancer registries and databases or from multiple clinics or hospitals. Regarding exposure assessment, studies were assigned two stars if the participants were identified through cancer registries, medical records and databases and one star if they self-reported their diagnosis. A response rate of 70% or more was considered as satisfactory. A study was assigned a star if additionally, reported data regarding differences between respondents and non-respondents. Studies were assigned one star if they used validated tools (e.g. screeners) to assess psychological distress, anxiety and depression and two stars if the AYAs were clinically diagnosed with any of the outcomes of interest based on the DSM criteria for mental disorders.  [K10_diff includes studies using the K10 instrument with different cut-offs; in the "Other" group, studies using infrequently used instruments were grouped together] BSI-18, Brief Symptom Inventory -18; DT, Distress Thermometer; HADS, The Hospital Anxiety and Depression Scale; K10, The Kessler Psychological Distress Scale -10; K6, The Kessler Psychological Distress Scale -6. eFigure 6. Meta-analysis results on prevalence of anxiety among AYA cancer survivors by geographical region (24 studies; 8751 participants). eFigure 7. Meta-analysis results on prevalence of anxiety among AYA cancer survivors by treatment status (24 studies; 8751 participants). eFigure 8. Meta-analysis results on prevalence of anxiety among AYA cancer survivors by assessment instrument and cut-off (24 studies; 8751 participants).
[Self-reported includes studies where participants self-reported a professionally diagnosed anxiety disorder; in the "Other" group, studies using infrequently used instruments were grouped together] SD, standard deviation; STAI, State-Trait Anxiety Inventory; HADS, The Hospital Anxiety and Depression Scale; GAD-7, Generalized Anxiety Disorder Scale -7; PSSCAN-R, The Psychosocial Screen for Cancer. eFigure 9. Meta-analysis results on prevalence of depression among AYA cancer survivors by geographical region (35 studies; 16638 participants). eFigure 12. Odds ratios (OR) and corresponding 95% confidence intervals (95%CI) investigating psychological distress among AYAs in comparison to older cancer survivors (1 study) and cancer-free peers (3 studies).
[Older cancer survivors were those diagnosed with cancer after 39 years of age] eFigure 13. Risk ratios (OR) and corresponding 95% confidence intervals (95%CI) investigating psychological distress among AYAs in comparison to older cancer survivors and cancer-free peers (1 study).
[The same study compared AYA with older cancer survivors and cancer-free peers; Older cancer survivors were those diagnosed with cancer after 39 years of age] eFigure 14. Odds ratios (OR) and corresponding 95% confidence intervals (95%CI) investigating anxiety disorders among AYAs in comparison to older cancer survivors (4 studies) and cancer-free peers or siblings (2 studies).
[Older cancer survivors were those diagnosed with cancer after 39 years of age] eFigure 15. Risk ratios (OR) and corresponding 95% confidence intervals (95%CI) investigating anxiety disorders among AYAs in comparison to cancerfree peers (1 study) and siblings (1 study).

eFigure 16. Odds ratios (OR) and corresponding 95% confidence intervals (95%CI) investigating depression and mood disorders among AYAs in comparison to younger cancer survivors (1 study) older cancer survivors (3 studies) and cancer-free peers or siblings (3 studies).
[Older cancer survivors were those diagnosed with cancer after 39 years of age; younger cancer survivors were those diagnosed with cancer during childhood] eFigure 17. Risk ratios (RR) and corresponding 95% confidence intervals (95%CI) investigating depression and mood disorders among AYAs in comparison to cancer-free peers (3 studies) and siblings (2 studies).  Both self-reports and clinical diagnosis (based on ICD-10 reporting, DSM-4 and 5) of the outcomes before, during and after treatment for cancer • Any anxiety disorder such as: generalized anxiety disorder (GAD), phobias, panic attacks or simply referred to as anxiety involving measuring of clinically significant symptoms such as "excessive anxiety, worry, fear, apprehension, and/or dread"* • Depression referred to as mood disorder, major depressive disorder or depressive symptoms such as "affect, sleep disturbance, and thought patterns"* • Psychological or emotional distress referring to a "multifactorial unpleasant experience of a psychological (i.e., cognitive, behavioral, emotional), social, spiritual, and/or physical nature that may interfere with one's ability to cope effectively with cancer"*, also identified as a summary measure of anxiety or depression