The effect of radioactive iodine (RAI) on disease-specific survival in differentiated thyroid cancer (DTC): A study of 96,557 patients.
Authors: Alshwayyat Sakhr Abdulsalam , Al-Akhras Ashaar , Ababneh Obada Ehab , Alshwayyat Tala Abdulsalam , Ghazou Alina 
Published: June 2023

e18095 Background: The use of RAI in the treatment of DTC of various stages and risk levels is widespread. However, its efficacy continues to be a subject of debate, particularly with regard to low-risk patients. Some studies have found significant differences in RAI's ability to decrease recurrence and distant metastasis, while others have not. Thus, we conducted this study to evaluate the effect of RAI on disease-specific survival (DSS) in patients with DTC without distant metastasis. Methods: Data were obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database between the years 2000 and 2018. Patients who have distant metastatic, tumor size ≥200 mm, receiving chemotherapy or any type of radiation other than RAI were excluded. Only patients with total thyroidectomy as surgical procedure were included. These patients were classified into three groups based on their histology: classical papillary thyroid carcinoma (C-PTC), follicular type variant carcinoma (FV-PTC), and follicular thyroid cancer (FTC). T-tests and chi-square tests were employed to compare variables, while the Cox proportional hazards model was utilized to assess the effect of RAI on DSS, presenting adjusted hazard ratios and confidence intervals. Results: The study population consisted of 96,557 patients, with 59,460 classified as having C-PTC, 31,583 as FV-PTC, and 5,489 as FTC. Most patients were female (78.6%), and the mean age was 45.8 years. 80.5% of the patients were white. The mean tumor size was 19.4 mm, with FTC tumors having a larger mean size of 34.8 mm. About a third of cases had an extrathyroidal extension. FV-PTC had the most favorable survival outcome with a 5-year DSS of 97.9%, followed by C-PTC (97.1%) and then FTC (96.9%). RAI was administered to 61.2% of FTC cases, 53.2% of C-PTC cases, and 52.1% of FV-PTC cases. In both FV-PTC and C-PTC, patients who received RAI had significantly better long-term survival than those who underwent surgery alone. The multivariable analysis confirmed that RAI had a more favorable prognosis in FV-PTC (HR = 0.68, 95%CI: 0.61 to 0.77, p<0.001) and C-PTC (HR = 0.60, 95%CI: 0.54 to 0.67, p<0.001), but did not result in improved DSS in FTC (HR = 0.87, 95%CI: 0.70 to 1.09, p = 0.226). There was a survival difference between the three histological subtypes in the overall cohort (p<0.001), even after matching baseline characteristics (p = 0.019). Conclusions: Our results showed that RAI administration was statistically associated with improved long-term DSS outcomes in FV-PTC and C-PTC histological subtypes, but not in FTC. However, a careful interpretation of these results is needed as the survival benefit was less than 3% in all cohorts, it might be clinically insignificant. This study was the first to examine all histological types of DTC using a large sample size. There is a need for a randomized trial to confirm the efficacy of RAI in FTC treatment.