Patient Selection for Radioactive Iodine Treatment

• 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