Cancer Risk after Radioactive Iodine Treatment for Hyperthyroidism: A Systematic Review and Meta-analysis

Importance: Whether radioactive iodine (RAI) therapy for hyperthyroidism can increase cancer risk remains a controversial issue in medicine and public health. Objectives: To examine site-specific cancer incidence and mortality and to evaluate the radiation dose-response association after RAI treatment for hyperthyroidism. Data Sources: The Medline and Cochrane Library electronic databases, using the Medical Subject Headings terms and text keywords, and Embase, using Emtree, were screened up to October 2020. Study Selection: Study inclusion criteria were as follows: (1) inclusion of patients treated for hyperthyroidism with RAI and followed up until cancer diagnosis or death, (2) inclusion of at least 1 comparison group composed of individuals unexposed to RAI treatment (eg, the general population or patients treated for hyperthyroidism with thyroidectomy or antithyroid drugs) or those exposed to different administered doses of RAI, and (3) inclusion of effect size measures (ie, standardized incidence ratio [SIR], standardized mortality ratio [SMR], hazard ratio [HR], or risk ratio [RR]). Data Extraction and Synthesis: Two independent investigators extracted data according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Overall quality assessment followed the recommendations of United Nations Scientific Committee on the Effects of Atomic Radiation. The SIR and SMRs and the RRs and HRs were pooled using random-effects meta-analysis. Main Outcomes and Measures: Cancer incidence and mortality for exposure vs nonexposure to RAI therapy and by level of RAI administered activity. Results: Based on data from 12 studies including 479452 participants, the overall pooled cancer incidence ratio was 1.02 (95% CI, 0.95-1.09) and the pooled cancer mortality ratio was 0.98 (95% CI, 0.92-1.04) for exposure vs nonexposure to RAI therapy. No statistically significant elevations in risk were observed for specific cancers except thyroid cancer incidence (SIR, 1.86; 95% CI, 1.19-2.92) and mortality (SMR, 2.22; 95% CI, 1.37-3.59). However, inability to control for confounding by indication and other sources of bias were important limitations of studies comparing RAI exposure with nonexposure. In dose-response analysis, RAI was significantly associated with breast and solid cancer mortality (breast cancer mortality, per 370 MBq: 1.35; P =.03; solid cancer mortality, per 370 MBq: 1.14; P =.01), based on 2 studies. Conclusions and Relevance: In this meta-analysis, the overall pooled cancer risk after exposure to RAI therapy vs nonexposure was not significant, whereas a linear dose-response association between RAI therapy and solid cancer mortality was observed. These findings suggest that radiation-induced cancer risks following RAI therapy for hyperthyroidism are small and, in observational studies, may only be detectable at higher levels of administered dose.