Age at Primary Malignancy Determines Survival in Adolescent and Young Adults That Develop a Secondary Thyroid Cancer

Second malignancy status is a risk factor for death in adolescent and young adults (AYAs) (ages 15-39) with thyroid cancer (TC). This study investigates whether age at primary malignancy (PM) is an independent predictor of overall survival (OS) for AYA patients diagnosed with secondary TC who have survived ≥5 years from their PM.

Surveillance, Epidemiology and End Results program (SEER) multiple-primary session (SEER-9 [1973-2010] and SEER-13 [1992-2010]) identified all secondary TCs in patients <40 years of age who were also 5-year survivors. Patients with a thyroid second malignant neoplasm (SMN) diagnosed as an AYA were categorized by age at PM (pediatric <15 years vs. AYA). Kaplan-Meier and Cox proportional analysis determined OS.

Four hundred twenty-eight cases of secondary AYA TCs in 5-year cancer survivors were identified; 71 had a pediatric PM and 357 an AYA PM. Median OS after a pediatric PM was 35.76 years and 33.22 years after an AYA-PM (p = 0.023); only one death was due to TC. Race, site and stage of PM, marital status, and three or more independent PMs also influenced OS (all p < 0.05). However, TC characteristics, stage, and treatment did not affect OS. Cox regression demonstrated that patients with an AYA PM had a 5.84 relative risk of death (95% confidence interval [95% CI]: 1.81-18.91) compared to patients with a pediatric PM. Among AYAs who develop a TC as a second PM, OS is not affected by the TC. The OS for these patients is associated with their demographics and the characteristics of their PM: patients who are black, male, have three or more primary cancers, and a higher stage of their first malignancy are more likely to die.

For AYA patients with thyroid SMNs, having a prior AYA PM (compared to a pediatric PM), Black race, and having three or more independent tumors predicted a decreased OS, independent of PM type or PM/SMN stage.