Psychological Outcomes in Adolescent and Young Adult Cancer Survivors

Abstract

The diagnosis of cancer during adolescence and young adulthood (AYA) may alter the development and psychological trajectory of survivors across their lifespan. The current review focuses broadly on emotional health, social functioning, health behaviors, and cancer-related cognitive impairment among AYA survivors. Overall, AYA survivors appear to be at elevated risk of emotional distress symptoms, mood and anxiety disorders, suicide, and mental health care service utilization compared to individuals without a cancer history. Difficulties with social relationships and reduced achievement of expected social outcomes including educational attainment and employment have been reported. Despite risk for health-related morbidities, including subsequent neoplasms, many AYA survivors do not engage in health behaviors at the recommended levels for physical activity, diet, or tobacco and alcohol use. While cancer-related cognitive impairment (CRCI) has not been comprehensively characterized in this population, subgroups of AYA survivors appear to be at-risk for experiencing CRCI including survivors of central nervous system tumors, Hodgkin lymphoma, testicular, and breast cancer. Across each considered domain of psychological functioning, intervention efforts have largely focused on acceptability and feasibility with an increasing focus on e/mHealth approaches. Future research should include multi-phase studies, including randomized controlled trials designed to evaluate intervention efficacy and effectiveness. It is imperative that psychological interventions consider the unique needs of AYA survivors by developmental stage and across multiple levels of influence (patient, support system, institution, health care system).

Introduction

Many cancer survivors experience adverse psychological outcomes secondary to their primary disease, treatment, and/or development of medical late effects. For individuals diagnosed with cancer as adolescents or young adults (AYAs), psychological functioning must be considered in the context of patient- (e.g., unique cancer diagnosis and treatment factors, developmental stage, social transitions and milestones), support system- (e.g., social support structure), institutional- (e.g., institutional resources [likely to vary by site of care]), and healthcare- (e.g., insurance policies) level factors characteristic of this population (Figure 1). While psychological functioning is comprised of multiple domains, these contextual factors pose unique challenges for AYAs related to emotional health, social functioning, health behaviors, and cognition. For example, acute adjustment difficulties secondary to diagnosis and treatment may be exacerbated by lack of AYA-specific treatment protocols and clinical trials at an institution as well as whether treatment occurs in a pediatric or adult setting.¹ Unique development factors characteristic of adolescence and young adulthood including goals of establishing autonomy, pursuing higher education, starting a career and becoming financially independent, forming romantic relationships, and having children may contribute to or lead to unique psychological challenges. Challenges in psychological functioning may persist beyond treatment completion well into survivorship and providing optimal care for AYAs requires an understanding of their unique psychological needs and developmentally specific factors that should be considered to best promote optimal outcomes. The primary objectives of this paper are to (1) review research related to psychological outcomes for survivors of AYA onset cancers with a focus on emotional health, social functioning, health behaviors, and cancer-related cognitive impairment, and (2) highlight potential intervention targets, considerations, and emerging intervention approaches within this population.

Figure 1.

Conceptual framework of multilevel factors influencing key psychological outcomes in AYA survivors.

Emotional Health

Most studies on mental health outcomes in AYA survivors have focused on symptoms of emotional or mental distress. An early review of the literature reported that rates of clinical distress among AYAs with cancer ranged from 5% to 57%.² A more recent estimate suggests that up to one-third of AYA survivors experience moderate-to-severe symptoms of anxiety and depression, and up to half experience clinically significant symptoms of posttraumatic stress within 6 to 24 months of diagnosis.³ However, while some studies report that AYA survivors experience greater distress symptoms than the general population or normative expectations,⁴ others report no differences.⁵ Nonetheless, female sex is consistently associated with report of greater distress symptoms among AYA survivors.³

Few studies have considered psychiatric disorders beyond acute mental health symptoms as an outcome. A meta-analysis of psychiatric disorders in AYA cancer survivors found only three eligible studies and reported increased risk of anxiety and mood disorders compared to cancer-free controls, with female sex and older age at diagnosis emerging as risk factors.⁶ A population-based cohort study of >12,000 AYA survivors estimated the incidence of any psychiatric disorder to be 61%, with anxiety disorders (49%), mood disorders (42%), and trauma and stressor-related disorders (19%) being the most common.⁷ In a study of >2,200 AYA survivors (age 15–21 years), higher rates of outpatient mental health visits, severe psychiatric episodes, and psychotic disorder-associated severe events (i.e., mental health related emergency department visit or hospitalization or completed suicide) were observed compared to matched controls.⁸ Notably, survivors treated at adult centers experienced higher outpatient mental health visit rates compared to survivors treated at pediatric settings.⁸

Suicide is a serious potential consequence of poor emotional health or distress. Risk of suicidal ideation⁹ and death by suicide appear to be higher among AYA survivors compared to the general population.¹⁰ AYAs who identify as White, are not currently married, and with metastatic disease have higher rates of suicide than other AYA survivors.^10,11 AYAs diagnosed with cancers of the head and neck and testicular cancer are also at an increased risk of suicide than AYAs with cancers of other disease sites.¹¹ Other aspects of emotional health that are particularly salient for AYA survivors include fear of cancer recurrence, intolerance of uncertainty, body image concerns, sexual dysfunction, and fear of social rejection or stigmatization.

Intervention studies to improve emotional health outcomes specific to AYA survivors have primarily focused on acceptability, feasibility, and safety with an increasing emphasis on e/mHealth approaches. A recent systematic review and meta-analysis examined online interventions to improve the mental health of pediatric and AYA survivors.¹² Only thirteen studies met inclusion criteria; six of which focused on physical activity enhancement. Overall, the thirteen online interventions reviewed were efficacious at improving sleep and general well-being, but not at reducing symptoms of depression, anxiety, and pain. A similar review and meta-analysis of technology-assisted psychosocial interventions for pediatric and AYA survivors found favorable intervention outcomes for childhood cancer survivors, but limited support for AYA survivors.¹³ Recruitment challenges also have been noted for group or peer-based interventions designed for the AYA population. Table 1 provides examples of emerging interventions to improve emotional health outcomes for AYA survivors.

Table 1.

Emerging interventions for AYA survivors across domains of psychological health

Emotional Health
Author, year	Study Design	Sample Characteristics	Skills Targeted	Intervention	Key findings
Salsman et al., 202368	Single-arm pilot feasibility	n = 44 Mean age = 30.8 years (range: 18–39)	Positives emotions (gratitude; mindfulness; positive reappraisal; goal setting; acts of kindness)	5-week eHealth positive emotion skills training (EMPOWER)	77% of invited survivors declined participation 79% adherence at 8 weeks 61% retention at 12 weeks 8 weeks: increased global mental health, meaning and purpose, and social function; decreased anxiety and anger 12 weeks: increased global mental health, meaning and purpose, positive affect, life satisfaction, self- efficacy, social function; decreased anger, sleep disturbance, fatigue
Zhang et al., 202269	Pilot randomized controlled feasibility study	n = 17 Mean age = 20.2 years (range: 15–26)	Depression; anxiety	Eight-week coach-assisted online cognitive behavioral therapy (MYTH) vs. active control (Beating the Blues)	80% completed 6/8 MYTH sessions MYTH group had significantly greater post-treatment depression scores (between group effect size = 1.12)
Rosenberg et al., 201870; 202171	Phase 2 randomized controlled trial	n = 92 73% were 12 to 17 years (range: 12–25)	Stress management; goal setting; cognitive reframing; meaning making	Four, 30-to-50- minute, one-on-one sessions delivered every other week, skill-based intervention (PRISM) vs. usual care	90% completed 4 PRISM sessions 6 months: PRISM group reported higher resilience and cancer- specific quality of life; reduced psychological distress Survivors who responded to PRISM in first 6 months sustained improvements at 24 months
Social Functioning
Author, year	Study Design	Sample Characteristics	Skills Targeted	Intervention	Key findings
Sleeman et al, 202223	Development and initial evaluation of a social support app	n = 141 AYAs Mean age = 28.8 years (eligible range 18–39) n = 37 loved ones Mean age = 39.9	Social support	Co-creation and initial usage of AYA Match app	Reasons for downloading app: AYA: 23.4% staying in contact; 21.5% share needs and wants with others Loved ones 68.6% stay in contact with AYA; 68.6% know the needs and wishes; 60% know how to help AYA
Health Behaviors
Author, year	Study Design	Sample Characteristics	Skills Targeted	Intervention	Key findings
Schwartz et al., 201939	Feasibility pilot randomized controlled trial	n = 61 Mean age = 16.8 years (intervention group) (range: 12–21) 17.7 years (control group) (range: 13–24)	Health Behaviors (smoking, physical activity, sunscreen use, diet, sleep)	16-week intervention including daily text messages (THRIVE) vs. AYA survivor handbook	78% enrollment 89% retention 70% reported they received “just the right amount of texts” 100% would recommend to a friend THRIVE group increased fruit/vegetable consumption
Cognitive Impairment
Author, year	Study Design	Sample Characteristics	Skills Targeted	Intervention	Key findings
Muthumuni et al., 202372	Single-arm pilot feasibility	n = 12 Mean age = 33 years (range: 24–40)	Memory skills, task management, psychological well- being	8-week 90-minute virtual group sessions on psychoeducation on CRCI (Coping with Brain Fog)	Adherence: 92% (not missing >2 consecutive sessions) Qualitative interviews indicated acceptance and utility of intervention 6–8 weeks post-intervention: clinically meaningful increase in self-perceived cognitive function; significant decrease in distress related to cognitive problems
Gooch et al., 202273	Two-arm pilot feasibility	Intervention arm n=7 Non-intervention arm n=7 Mean age = 15 years (range: 12–25)	Memory; attention	16-week daily computerized prevention cognitive rehabilitation (Lumosity) vs. no intervention	Adherence: 71% (completion of at least 80% of sessions) A greater proportion of patients in the non-intervention group impaired on processing speed, visual attention, and working memory at end of study

Social Functioning

At its core, social functioning describes how an individual interacts with their environment, including fulfillment of their roles across relationships, activities, and obligations. For AYA survivors, social functioning is a central component of health-related quality of life (HRQoL) and includes engagement in social roles as well as acquisition of social support. AYAs with cancer may experience disruptions in many aspects of social functioning as a result of their cancer treatment,¹⁴ though the extent of the impact is likely to vary due to patient-level factors such as specific diagnosis, intensity of treatment required, and developmental stage at which the diagnosis is rendered.

Much of the research on social functioning among AYAs consists of either large samples using broadband measures of HRQoL (e.g., Pediatric Quality of Life Inventory [PedsQL], Functional Assessment of Cancer Therapy [FACT], Medical Outcomes Study Short Form 36 Health Survey [SF-36]),^15,16 or small sample qualitative reports. Most studies are single informant (patient only), with very few seeking input from proxies (e.g., friends, parents, partners, etc.). Because adolescence and young adulthood is a period of significant developmental transitions in which AYAs are becoming increasingly independent, spending more time with their friends and less time with their family of origin, and relying more heavily on peers for social support, the social needs of AYAs are likely to vary considerably by their developmental stage. As the AYA period encompasses adolescents (15–18), emerging adults (18–25) and young adults (25–39), understanding an individual’s social roles, family of origin involvement, treating hospital environment, family roles (parenting, partnerships), and educational/vocational status is critical to understanding how to assess and intervene to improve social functioning in this population.

Social functioning research to date has primarily focused on younger AYAs in the adolescent or emerging adult group, with significantly less research focused specifically on young adults.17 A qualitative study of young adults (25 to 39 years) indicated numerous unique practical and social issues – including balancing treatment with other life responsibilities (work, childcare), wanting to retain a sense of normalcy and focus on personal identity that didn’t involve being a cancer patient, social isolation, and uncertainty.¹⁷ In the social sphere, these AYAs discussed distancing from current friends, as well as uncertainty and hesitancy for making new ones, especially with regards to disclosure of their diagnosis. They also described difficulties engaging with other cancer patients due to dissimilarities in age (i.e. being much younger than most other adult patients in their clinic). As a result, key differences in the social experiences across AYA groups mean that strategies to support social functioning developed for younger age groups are unlikely to generalize to older AYAs.

Although limited, longitudinal observational studies suggest that AYAs endorse poor social functioning at baseline that improves over time, but remains reduced as compared to population-based normative data.^15,16 Interestingly, a study of 215 AYAs noted that nearly one-third of survivors endorsed consistently low social functioning from the time of diagnosis through a 24 month follow-up.¹⁵ The 32% of AYAs reporting consistently low social functioning were less likely than AYAs with improving, consistently high, or worsening social functioning to report being employed and/or in school, either at baseline or at follow-up, indicating that involvement in age-appropriate social roles may be particularly essential for promoting social functioning during survivorship.

With regards to engagement in age-appropriate social roles, there has been significant work describing the impact of an AYA cancer diagnosis on work, education, and financial outcomes.^18–21 A recent systematic review indicated that, compared to the general population, AYA survivors are more likely to be unemployed, earn less, and use government benefits.¹⁸ Female sex, diagnosis of a brain tumor or lymphoma, advanced disease, and/or report of cognitive impairment predicted poorer vocational and financial outcomes. An additional notable predictor was quitting work or school directly after diagnosis,¹⁹ highlighting the importance of remaining involved in age-appropriate activities during treatment to optimize social attainment.

From an intervention standpoint, there has been limited literature focused on improving AYA social functioning after a cancer diagnosis. The primary focus of interventions to-date has been on increasing social support, sometimes in combination with another intervention target (e.g., mindfulness).^22,23 While the feasibility of these approaches has been demonstrated; larger randomized trials to evaluate efficacy have not yet been conducted (Table 1).

Health Behaviors

Engaging in healthy lifestyle behaviors has the potential to mitigate the increased risks of subsequent cancers, chronic medical conditions, and excess mortality faced by AYA survivors.²⁴ As a result, multiple professional organizations recommend that AYAs participate in regular physical activity, follow healthy eating patterns, avoid substance use (i.e., tobacco/vaping, alcohol, illicit drugs), and practice sun protection.^25,26

Physical Activity

Engaging in regular aerobic exercise and strength training improves functional outcomes (i.e., aerobic capacity and endurance, muscle strength, muscle endurance)²⁷ and AYAs who achieve physical activity guidelines (150 minutes of moderate physical activity, 75 minutes of vigorous physical activity, or a combination of these each week) report better mental health, lower stress, and fewer depressive symptoms than those who are more sedentary.²⁸ Unfortunately, physical activity decreases following cancer diagnosis for many AYAs²⁹ and over one-third of AYA survivors do not meet physical activity guidelines.^29–32 While data regarding predictors of physical activity are mixed,³³ higher income,³¹ postsecondary education,³¹ and gym access³⁰ have been associated with higher levels of physical activity, suggesting that resources and access may play a key role in this behavior. Available physical activity interventions for AYA survivors demonstrate limited efficay^34–36 and there is a critical need for additional physical activity intervention development, evaluation, and implementation efforts. As interventions to date have largely focused on self-directed, home-based programs and tailored, supervised aerobic exercise and strength training programs that include partnerships with rehabilitation professionals (i.e., exercise physiologists, occupational therapists, physical medicine and rehabilitation medical teams, physical therapists) have improved outcomes in other populations, a promising future direction for the field may include the development and evaluation of integrated physical activity programs.³⁶

Dietary Behavior

During cancer treatment, an AYA’s dietary behavior may change in response to cravings (e.g., for energy dense foods high in sugar or salt), aversions (e.g., due to feelings of nausea), and access (e.g., food available at/near treating hospital). Such changes may begin to explain why less than half of AYA survivors meet dietary guidelines regarding fruit/vegetable intake^29,37,38, fat,²⁹ sugar,²⁹ and/or processed meat.²⁹ While research suggests many AYAs feel they should have a healthier diet,²⁹ available interventions are still in the pilot stages of testing^39,40 and an important next step includes the elucidation of modifiable predictors of dietary behavior that could serve as intervention targets as well as large-scale testing of existing and novel interventions (Table 1, Table 2).

Table 2.

Potential intervention targets across domains of psychological health and cross-cutting considerations for intervention development and implementation

Domain	Potential Targets	Cross-Cutting Considerations
Emotional Health	Anxiety Depression Post-traumatic stress Suicidality Self-efficacy Fear of cancer recurrence Body image	Patient Level  • Developmental stage during treatment (cognitive, social, and emotional)  • Developmental stage at time of intervention (cognitive, social, and emotional)  • Culturally specific social transitions and milestones  • Time since diagnosis/treatment completion  • Treatment-related factors (e.g., acute toxicities, treatment stage)  • Limitations (functional or cognitive) resulting from treatment (e.g., amputation)  • Chronic health conditions (physical and mental health)  • Additional roles (e.g., student, employee, parent/caregiver) and related goals Support System Level  • Support person (e.g., parent/peer/partner)  • Social network and involvement Institution Level  • Institutional resources (e.g., survivorship clinic)  • Institutional expertise  • Accessibility (e.g., m/eHealth applications) Healthcare System Level  • Resources and access (e.g., insurance policies)
Social Functioning	Peer relations Family relations Social network/integration Social isolation/loneliness Social support (instrumental/informational)
Health Behaviors	Physical activity Sedentary behavior Diet Tobacco use Vaping Alcohol consumption Sun exposure Sexual activity Sleep
Cancer-Related Cognitive Impairment	Attention Memory Processing speed Motor function Executive function Adaptive function

Substance Use

Tobacco use during adolescence and young adulthood is associated with early health consequences (i.e., reduced lung growth, reduced lung function, early cardiovascular damage)⁴¹, an increased likelihood of developing co-morbid conditions, and lower quality-of-life.⁴² Rates of tobacco use vary across countries and cohorts, with recent studies suggesting that 2–33% of AYA survivors currently smoke cigarettes.^{29,32,37,38,42} As tobacco companies continue to develop new flavors (e.g., sweet/fruity e- cigarettes), packaging, and delivery systems (e.g., vaping devices), there remains a need to understand the use of these products among AYA survivors, particularly as a recent study of AYA survivors receiving care in Chicago found that over half had used one or more other nicotine products (Hookah: 50%; cigar: 37%, little cigar: 32%; e-cigarette: 20%).⁴³ Unfortunately, behavior change techniques that drive smoking cessation intervention efficacy in general populations do not appear to improve outcomes among cancer survivors.⁴⁴ Recognizing the need for innovative interventions that address the unique barriers faced by cancer survivors, the National Cancer Institute launched the Cancer Center Cessation Initiative and results of these efforts are likely to yield important implications for the AYA survivorship community.

Alcohol consumption is associated with an increased risk of developing several types of cancer and amid growing evidence supporting this association, the American Cancer Society recently revised their guidelines to indicate that “it is best not to drink alcohol.”²⁵ Results from a recent study of AYA survivors receiving care in Chicago suggest that most AYA survivors do not achieve this guideline, with only 20% abstaining from alcohol use in the past year.⁴³ As the majority of research to date has focused on AYAs who engage in binge drinking (estimated 8–15%^37,38 of AYA survivors), predictors of and interventions for achieving this guideline remain unknown.

Substance use also includes the use of illicit drugs and/or prescription medications not as recommended (e.g., opioids). While data regarding these behaviors among survivors diagnosed with cancer as AYAs is limited, a recent study of AYAs with a history of cancer suggest 10–12% have misused prescription drugs (i.e., opioids) and 11% have used opioids.⁴⁵ Future research including additional substances beyond tobacco and alcohol is needed to understand the prevalence and impact of these health behaviors, particularly within the context of the rapidly changing drug landscape.

Sun Exposure

Melanoma is one of the most common second malignant neoplasm among AYA cancer survivors⁴⁶ and to reduce the risk of melanoma and other skin cancers, it is recommended that AYAs limit exposure to ultraviolet (UV) radiation. Although limited, data suggest that approximately one-third of AYA survivors demonstrate high adherence to sun exposure guidelines⁴⁷ and an important future direction is to explore whether skin cancer prevention interventions developed for the general population can also promote behavior change among AYA survivors.

Cancer-Related Cognitive Impairment

While cancer-related cognitive impairment (CRCI) has not been comprehensively characterized among AYAs, it is estimated to affect between 25% and 40% of AYA patients and survivors depending on the types of treatments received and the age at therapy.^48–50 CRCI commonly manifests as impairments in the domains of memory, attention, processing speed, and executive function. CRCI is an important and distressing symptom, particularly among AYA patients and survivors who are navigating important life transitions and milestones such as returning to school, establishing a career, developing social and/or romantic relationships, and/or establishing financial independence; all of which require varying cognitive demand and skills. Unsurprisingly, CRCI has been associated with reduced workability and employment among survivors of AYA cancers.^51,52 There have been few studies of CRCI among patients diagnosed during the AYA period; almost all of which have focused on subjective self-report of cognitive symptoms. Data from the US National Health Interview Study demonstrate that 24% of survivors of AYA cancer self-reported cognitive difficulties compared to only 15% in the general population. This was as high as 81% percent among survivors of AYA central nervous system tumors.⁵⁰ In a cohort of AYAs with cancer in Singapore, 34% of patients self- reported cognitive impairment during treatment.⁵³ 18% of patients in the AYA Leipzig Study self- reported cognitive impairment up to four years post-treatment.⁵¹ A report from the Childhood Cancer Survivor Study detailed that long-term survivors of adolescent and early young adult cancers (15 to 24 years at diagnosis) self-reported significant impairments in task efficiency, memory and emotional regulation.⁵² To our knowledge only one study has utilized objective neurocognitive testing to evaluate CRCI in a group of AYAs with cancer. Prior to any cancer treatment 40% of AYAs met the criteria for impairment (<2SD below the mean or <1.5SD below the mean on ≥2 neuropsychological tests) compared to only 14% of controls, thus demonstrating the impact of the primary tumor/disease on CRCI.⁴⁹

Characterizing CRCI among AYAs with cancer remains a challenge due to the heterogeneity of cancer diagnoses and treatments in this age group.⁴⁸ In fact, much of our understanding of the potential for CRCI in this group is inferred from studies of children and adolescents or adults with breast cancer. Studies that have tried to examine AYAs as a whole have not reported large differences in CRCI compared to non-cancer peers, likely because they have been underpowered given the heterogeneity of their samples.^50,51 Therefore, many studies have focused on diagnostically homogenous groups. Hodgkin lymphoma (HL) is the most common cancer in adolescence and one small study reported that 30% of HL a median of 2 years post-treatment were impaired ≥2 neurocognitive domains.⁵⁴ These impairments may persist as studies of long-term survivors (>10 years) of adolescent and early young adult HL self- report significant neurocognitive impairment decades after treatment.⁵⁵ In young adulthood, solid tumors become more common, namely thyroid, testicular, and breast cancers. While not conducted exclusively among AYA patients, several small studies indicate survivors of thyroid cancer experience neurocognitive impairment during therapy.⁵⁶ The mainstays of treatment are thyroidectomy, radioactive iodine, and thyroid hormone treatment. Thus, treatment-related hypothyroidism may contribute to CRCI in this population as hypothyroidism has been linked to mild cognitive impairment and dementia in the general population.⁵⁶

A number of studies have demonstrated that testicular cancer survivors experience significant impairments in memory, processing speed, executive function, and attention with effects exacerbated among those who received chemotherapy +/− radiation.^57,58 However, several studies of long-term survivors of testicular cancer report little difference between surgery only and surgery plus chemotherapy groups, suggesting that hypogonadism may contribute to long-term impairments.^57–59 The association between hypogonadism and cognitive impairments in testicular cancer survivors was recently confirmed in a cohort of survivors on average 26 years post treatment.⁶⁰

Lastly, while the majority of adult CRCI research has been conducted in patients with breast cancer, few studies have focused exclusively on AYAs with breast cancer. A French cohort followed AYAs with breast cancer up to 28 months post diagnosis and reported that the prevalence of self-reported memory loss and attention deficits was 42%.⁶¹ Several studies have looked at premenopausal women with breast cancer treated with chemotherapy or tamoxifen reporting impairments in executive function, verbal memory, and processing speed.^62,63

In summary, a large subset of AYAs with cancer experience CRCI that impacts their ability to return to work or school, their social relationships, emotional health, and quality of life. Future research should aim to characterize CRCI among AYAs in large longitudinal studies powered to accommodate the heterogeneity of diagnoses and treatments in this group. Intervention studies for CRCI have been limited (see Table 1) and should carefully consider the varying developmental stages of cognitive abilities and brain structures as well as external cognitive demands (school vs. work) as these vary throughout the AYA period.

Conclusions

While the field of AYA oncology is relatively new, it is increasingly clear that following active treatment, AYAs face unique psychological challenges with the potential to impact their mental health, quality of life, physical health, and successful achievement of life transitions and milestones. Results of this review suggest rates of psychological challenges differ across domains, studies, and populations, but a large proportion of AYAs endorse significant mental health symptoms, social functioning concerns, non- adherence to health behavior recommendations, and/or cognitive-related impairment during survivorship.

Results of our review identified several demographic and clinical factors associated with adverse psychological health. For example, female sex and metastatic disease have been associated with increased risk of emotional distress and reduced social attainment outcomes. Compared to survivors with other cancer types, survivors of head, neck, and testicular cancers appear to have elevated risk of suicide, while central nervous system tumor survivors have heightened risk of reduced social functioning and cognitive impairment. Cancer-related cognitive impairment is also prevalent among survivors of thyroid, testicular, and breast cancer, and appears to be driven by both specific treatment exposures as well as the development of treatment-related chronic health conditions. Notably, many AYA survivors develop chronic physical health comorbidities following receipt of cancer-directed therapies,⁶⁴ and this symptom burden may result in increased emotional distress, substance use to manage symptoms, and further exacerbate cognitive impairment.

Recognizing the prevalence and burden of potential psychological challenges following treatment for AYA onset cancers, experts (i.e., National Comprehensive Cancer Network) recommend assessing multiple domains as part of standard clinical care.⁶⁵ However, data on the effectiveness of various screening measures and the implementation of screening programs are extremely limited among AYAs with cancer. Additional measurement and implementation science research is needed to understand which screening measures are most useful, acceptable, and feasible, and how to scale these efforts to capture all patients and survivors while considering the unique characteristics of each institution (e.g., staffing, resources). The ongoing efforts to standardize a core set of patient reported outcomes and encourage their integration into cancer clinical trials (NCTN Adolescent and Young Adult Patient Reported Outcomes Battery⁶⁶) may offer important lessons for the development of a screening algorithm to monitor AYAs for early detection of potential psychological concerns.

Unfortunately, evidence-based interventions to address these concerns are limited and there is a critical need for novel and engaging interventions. To meet the complex and unique needs of AYA survivors, multi-phase efforts consistent with the ORBIT model of behavioral intervention development⁶⁷ are recommended to identify modifiable intervention targets, tailor and refine interventions to meet the unique needs of the target patient populations (e.g., older versus younger AYAs; populations with greater sociodemographic diversity), and ultimately evaluate these interventions in efficacy and effectiveness trials.

Based upon our current review of the literature, promising next steps for the field with the potential to optimize the psychological health of AYA survivors may include the development or refinement of interventions targeting the modifiable factors detailed in Table 2. Maximizing participant engagement and intervention reach, uptake, and effectiveness to ultimately enhance the potential impact of future interventions on AYA survivors is likely to require efforts to address the heterogeneity of patient-, support system-, institution-, and healthcare system-level factors characteristic of this age group. For example, to increase the likelihood that interventions can be delivered across the variety of settings where AYAs receive care, we encourage researchers to consider institution-specific implementation- related factors (e.g., personnel required to deliver intervention, resources required to deliver/receive intervention) during the intervention development process. As another example, AYAs may have a variety of social support networks depending on their diagnosis- and treatment-related factors (e.g., AYAs who moved from independent living to residing with their family of origin due to a demanding treatment regimen), current phase in their transition to independence, and impact of treatment on physical and cognitive functioning (i.e., physical limitations such as amputation). To accommodate these differences, researchers should consider interventions that allow for flexibility and tailoring in caregiver/support person involvement (e.g., allowing AYA to determine if they would like to involve a caregiver/support person; allowing AYA to select the caregiver/support person to involve). In all, our understanding of the emotional health, social functioning, health behaviors, and cancer-related cognitive impairment of AYA survivors is rapidly evolving, but there remains a significant opportunity to support AYAs across these domains to ultimately improve psychological functioning and quality of life for survivors.

Context summary.

Key objective:

What are common psychological outcomes experienced by AYA cancer survivors?

Knowledge generated:

A large proportion of AYA cancer survivors experience symptoms of emotional distress, reduced social outcomes, do not engage in recommended health behaviors, and subgroups are at-risk for developing cancer-related cognitive impairment. Targeted behavioral interventions, evaluated in the context of randomized clinical trials, are needed to optimize psychological health of survivors.