Multimorbidity Among Adolescent and Young Adult Thyroid Cancer Survivors: A Report From the AYA VOICE Study

Background: Thyroid cancer is one of the most common cancers in adolescents and young adults (AYA, 15 to 39), with excellent 5-year survival of 98%. However, treatments for thyroid cancer such as radioactive iodine and thyroid hormone suppression may increase the risk for multiple late effects (LE). We investigated the incidence of severe LE that cluster in AYA thyroid cancer survivors in a large population-based cohort. Methods: We used California Cancer Registry records to identify AYAs diagnosed with first primary thyroid cancer during 2006–2018 linked to statewide hospitalization, ambulatory surgery, and emergency department data. Cohort entry began 2 years from diagnosis. Severe LE included cardiovascular, respiratory, endocrine, renal, and liver diseases, and second cancers. Cumulative incidence of each LE, accounting for the competing risk of death, was calculated. Latent class analysis (LCA) identified clustering of LE overall and in <5 and ≥5-year survivors. The number of LE classes was identified by selecting models with the lowest likelihood-ratio G2 statistic, Akaike's Information Criterion, and Bayesian Information Criterion. Probabilities of each LE are presented in each class. Results: Of 12,224 survivors, 83% were female, 34% were Hispanic, and 62% aged 30–39 years at diagnosis. Mean follow-up time was 7.9 years. Five-year cumulative incidence was highest for endocrine (27.9%, 95% CI 27.0–28.8), respiratory (5.1%, 95% CI 4.6–5.5), and cardiovascular (2.1%, 95% CI 1.8–2.4) diseases. The LCA model identified 3 classes: 78.6% were ‘healthy survivors’ with a low probability of any LE, 19.8% experienced a high probability of endocrine (95%) conditions, and the remaining 1.6% were ‘multimorbidity survivors,’ experiencing a high probability of all LEs, particularly endocrine (94%), cardiovascular (61%), renal (55%), and respiratory (46%) conditions, followed by liver disease (25%) and second cancers (9%). No differences were found in the LCA classes among <5 and ≥5-year survivors. Conclusion: While most survivors of AYA thyroid cancer have few severe LEs, >20% have a high probability of endocrine conditions or multimorbidities. Multidisciplinary survivorship care may be vital to supporting thyroid cancer survivors experiencing multiple LEs.