• The decision to administer radioiodine after thyroidectomy in patients with differentiated thyroid cancer is based upon the clinicopathologic features of each case
• The efficacy of radioiodine depends upon:
• Tumor-specific characteristics
• Sites of disease
• Patient preparation
• Dose
• Because of the careful risk stratification used in some studies, it is possible to identify specific patient and tumor characteristics which suggest that radioiodine may be beneficial:
• My approach outlined below is in agreement with the American Thyroid Association (ATA) guidelines on the role of postoperative radioiodine ablation:
• Low risk:
• The ATA guidelines do not routinely recommend administration radioiodine after lobectomy or total thyroidectomy to low-risk patients with differentiated thyroid cancer:
• This includes patients with:
• Unifocal cancer less than 1 cm without other high-risk features (eg, without distant metastases, vascular invasion, gross extrathyroidal extension, worrisome histologic subtypes):
• Even in the presence of small-volume regional lymph node metastases (less than five lymph nodes measuring less than 2 mm)
• Multifocal cancer when all foci are less than 1 cm and there are no other high-risk features:
• Without distant metastases
• Vascular invasion
• Gross extrathyroidal extension
• Worrisome histologic subtypes
• Intrathyroidal cancer in the 1 to 4 cm range without other high-risk features:
• Without distant metastases, vascular invasion, gross extrathyroidal extension, worrisome histologic subtypes
• Individual tumor- and patient-specific features may warrant radioiodine ablation in selected low-risk patients:
• As an example, low-dose radioiodine ablation (30 mCi) in low-risk patients with intrathyroidal tumors greater than 4 cm may be considered
• In a randomized trial evaluating post-thyroidectomy radioiodine (1.1 GBq [30 mCi] after recombinant human TSH [rhTSH]) or no radioiodine therapy in 730 patients with low-risk differentiated thyroid cancer (multifocal pT1a with the sum of the longest diameters less than 2 cm, or pT1b, both with N0 or Nx, and without aggressive pathological subtypes or extrathyroidal extension, outcomes at three years were similar in the two groups, including the following:
• Primary disease-related events (identification of residual or recurrent disease or an elevated level of thyroglobulin or thyroglobulin antibodies) at three years occurred in:
• 4.1% and 4.4% of patients, respectively
• The frequency of BRAF mutation did not differ between cases with or without disease-related events:
• 61.5% versus 53.1% respectively
• An ATA excellent response at 10 months and 3 years occurred in:
• 86.8% and 86.3%, respectively, after 10 months
• 73% and 74.1%, respectively, after 3 years
• Quality-of-life scores related to:
• Anxiety, distress, and fear of recurrence
• In systematic reviews and meta-analyses of observational data:
• There was no benefit of radioiodine in low-risk patients with regard to either:
• Overall recurrence rate or disease-specific mortality
• As an example, in a retrospective analysis of 1129 patients who underwent total thyroidectomy for differentiated thyroid cancer and received radioiodine based upon risk assessment:
• The majority of patients with low-risk local disease (age less than 45 years, papillary cancer less than 4 cm without extrathyroidal extension, and without distant metastases):
• Had low rates of recurrence and high rates of survival when managed without radioiodine;
• Five-year recurrence-free survival greater than 97%
• Another retrospective study similarly showed no benefit of radioiodine ablation on disease recurrence in patients with papillary thyroid microcarcinoma (unifocal or multifocal):
• In this study, there was no disease-related mortality
• Intermediate risk:
• The administration of radioiodine after total thyroidectomy is considered in selected intermediate-risk patients depending upon specific tumor characteristics, including:
• Microscopic invasion into the perithyroidal soft tissue
• Clinically significant lymph node metastases outside of the thyroid bed
• Other higher-risk features:
• Vascular invasion
• More aggressive histologic subtypes such as:
• Tall cell histology
• Columnar cell histology
• Insular histology
• Poorly differentiated histology
• When the combination of age, tumor size or multifocality, lymph node status, and individual histology:
• Predicts an intermediate to high risk of recurrence or death from thyroid cancer
• In the absence of evidence supporting survival benefit for all of the factors listed:
• Clinical judgment and an individualized approach to care are important
• Postoperative serum thyroglobulin is a critical factor that should be routinely integrated into clinical decision-making:
• For example, in a retrospective cohort study, there was no difference in the five-year recurrence-free survival among intermediate-risk patients who did or did not receive radioiodine therapy:
• When postoperative unstimulated serum thyroglobulin levels were less than 1 ng/mL
• There are limited data showing a benefit of radioiodine in intermediate-risk patients:
• In a study using the National Cancer Database registry, which included 21,870 patients with intermediate-risk papillary thyroid cancer who had total thyroidectomy with or without radioiodine:
• Patients who received radioiodine had improved overall survival (hazard ratio [HR] 0.71, 95% CI 0.62-0.82)
• In the National Thyroid Cancer Treatment Cooperative Study Group (NTCTCSG), a multicenter thyroid cancer registry that has analyzed the outcomes of nearly 5000 patients with differentiated thyroid cancer:
• Multivariable analysis showed that radioiodine ablation was associated with:
• Improvement in overall survival in stage II patients:
• But this did not reach statistical significance (relative risk [RR] 0.67, 95% CI 0.36-1.28)
• High risk:
• Based on the ATA guidelines high risk patients are routinely treated with radioiodine after total thyroidectomy, including patients with:
• Distant metastases
• Macroscopic tumor invasion,
• Incomplete tumor resection with gross residual disease
• In the National Thyroid Cancer Treatment Cooperative Study Group:
• Radioiodine was associated with improved overall survival in stage III patients (RR 0.66, 95% CI 0.46-0.98), with similar but nonsignificant improvement in stage IV (RR 0.70, 95% CI 0.46-1.10)
• In addition, data prospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database showed:
• Benefit from radioiodine in patients older than 45 years with primary tumors greater than 2 cm, with disease in the lymph nodes at initial diagnosis, and with distant metastatic disease
• The benefits and dose limits of iodine-131 (131-I) therapy for metastatic disease were evaluated in a retrospective analysis of 444 patients treated between 1953 and 1994 (analysis of whole-body iodine scans and conventional radiographs):
• 43% of the 295 patients with radioiodine uptake achieved resolution of radioiodine-avid metastases on iodine scan and negative conventional radiographs
• Additional features of patients in this group included the following:
• They were more likely to be younger:
• With differentiated tumors
• 96% of these patients were given cumulative doses of 100 to 600 mCi (3700 to 22,000 MBq)
• 7% had a recurrence
• 10-year survival was 92% in this group:
• Compared with only 19% in patients who did not achieve resolution of the radioiodine-avid metastatic lesions