Age-Specific Risk of Second Primary Malignant Neoplasm After Radioactive Iodine Treatment for Differentiated Thyroid Cancer.

Importance: Radioactive iodine treatment for differentiated thyroid cancer has been associated with second primary malignant neoplasms, but age-specific risks remain poorly understood. Objective: To evaluate the association of age with increased risk of second primary malignant neoplasm after radioactive iodine treatment for differentiated thyroid cancer (DTC). Design, Setting, and Participants: This retrospective cohort study used data from 8 cancer registries in the US National Cancer Institute's Surveillance, Epidemiology, and End Results Program for 1975 to 2021. Patients who received radioactive iodine treatment for DTC were identified; those with fewer than 2 years of follow-up, missing follow-up data, or distant metastases at diagnosis were excluded. Included patients were categorized into 3 age groups: 15 to 44, 45 to 64, and 65 years or older. Among 5-year survivors, median (IQR) follow-up time was 14.7 (8.6-24.0) years in the 15- to 44-year age group; 8.3 (6.4-11.4) years in the 45- to 64-year group; and 9.3 (6.9-12.7) years in the 65 years or older group. Data were analyzed from May to July 2024. Exposure: Radioactive iodine vs no radioactive iodine. Main Outcomes and Measures: Relative risks (RR) and 95% CIs for solid and hematologic second primary malignant neoplasms, calculated using multivariable Poisson regression models adjusted for age, sex, and latency. Results: The study sample comprised 72 412 patients with nonmetastatic DTC, of whom 28 432 (39%) were age 15 to 44 years; 34 009 (47%), age 45 to 64 years; and 9971 (14%), 65 years or older. In the 15- to 44-year age group, radioactive iodine was associated with an increased risk of hematologic cancers (RR, 1.35; 95% CI, 1.02-1.80), specifically myeloma (RR, 4.22; 95% CI, 1.68-10.62). In the 45- to 64-year age group, the analyses showed increased risks of prostate cancer (RR, 1.61; 95% CI, 1.10-2.37), salivary gland cancer (RR, 10.22; 95% CI, 1.27-82.24), and nodal non-Hodgkin lymphoma (RR, 2.81; 95% CI, 1.34-5.89). The overall risk of a solid second primary malignant neoplasm was not elevated (RR, 0.94; 95% CI, 0.76-1.16), but hematologic second primary malignant neoplasm risk was elevated (RR, 1.73; 95% CI, 1.14-2.60). Patients in the group that was 65 years and older showed elevated risks of stomach (RR, 4.06; 95% CI, 1.05-15.81), esophagus (RR, 11.42; 95% CI, 1.40-93.3), nonepithelial skin cancers (RR, 10.52; 95% CI, 1.09-88.77), and acute myeloid leukemia (RR, 3.26; 95% CI, 1.15-9.24). The overall risk of a solid second primary malignant neoplasm was elevated (RR, 1.88; 95% CI, 1.59-2.21), whereas risk of hematologic malignant neoplasm was not (RR, 1.35; 95% CI, 0.97-1.87). Conclusions and Relevance: This cohort study found that the risk of radioactive iodine-associated second primary malignant neoplasm among patients who received radioactive iodine for DTC varies significantly by age group, with distinct patterns in middle-aged compared with older adults. These findings suggest a need for age-specific surveillance strategies in radioactive iodine-treated DTC survivors. Further research is needed to establish optimal screening protocols.