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Simple Summary: The use of radioactive iodine (RAI) for the treatment of patients with thyroid cancer at intermediate risk of recurrence is controversial. Evidence to date has not conclusively proven that there are benefits of this strategy to survival or recurrence after surgery for thyroid cancer. We describe key elements that can help clinicians decide when to prescribe RAI to this group of patients. These include a thorough discussion of the purpose of RAI therapy, better prediction of recurrence risk, the use of tumor markers after surgery, the use of the genetic profile of the tumor when available, and a detailed evaluation of the adverse effects of RAI, patient medical problems, and patient preferences. Integration of these variables will ensure a more comprehensive assessment of the risks and benefits of RAI treatment with the ultimate goal of avoiding overtreatment and reducing harm. The use of radioactive iodine (RAI) after total thyroidectomy for patients at the American Thyroid Association (ATA) who are at intermediate risk of recurrence is controversial. This is due to the lack of prospective randomized trials proving a benefit to recurrence or survival of RAI therapy in this group. In the absence of such evidence, clinicians struggle to recommend for or against this therapeutic approach which frequently results in overtreatment. This review describes key elements in the decision-making process that help clinicians more comprehensively evaluate the need for RAI therapy in patients with thyroid cancer at intermediate risk of recurrence. A clear definition of the purpose of RAI therapy should be conveyed to patients. In this sense, adjuvant RAI therapy intends to decrease recurrence, and ablation therapy is used to facilitate surveillance. Better stratification of the intermediate risk category into a low–intermediate subgroup and an intermediate–high-risk subgroup results in less heterogeneity and a more precise prediction of recurrence risk. The evaluation of post-operative thyroglobulin levels may prevent the overtreatment of low–intermediate-risk patients when their thyroglobulin level is <2.5 ng/mL. the integration of tumor genomics (when available) alongside pathologic features can enhance the ability of the clinician to predict iodine concentration in thyroid cancer cells. Finally, a detailed consideration of the adverse effects of RAI, patients' comorbidities, and patient preferences will result in a patient-centered personalized approach. Systematic examination of these variables will ultimately provide a framework for making more educated decisions on the use of RAI in patients at intermediate risk of recurrence that will prevent overtreatment and minimize harm. [ABSTRACT FROM AUTHOR]

Background: The success of an active surveillance management approach to low-risk papillary thyroid cancer (PTC) is heavily dependent on proper patient selection. For example, primary tumors located in a subcapsular position immediately adjacent to the trachea or a recurrent laryngeal nerve (RLN) are considered to be inappropriate for active surveillance. Since preoperative imaging cannot reliably rule out extrathyroidal extension or reveal the full course of the RLN relative to the thyroid gland, it is important for clinicians to understand subcapsular tumor locations and minimum tumor sizes that are most likely to be associated with gross invasion of the RLNs. Methods: We assessed the medical records of 123 patients treated at Memorial Sloan Kettering Cancer Center (MSK) between 1986 and 2015 who had a primary PTC tumor demonstrating gross extrathyroidal extension to either the right or left RLN. Thirty patients with a primary tumor ≤2 cm in diameter demonstrating extrathyroidal extension into an RLN were included in the analysis. Results: Gross invasion of an RLN by tumors ≤2 cm is a rare event that was seen in only 0.8% (35/4334) of patients with PTC who underwent initial thyroid surgery at MSK between 1986 and 2015. Gross RLN invasion was associated with subcapsular PTC tumors located in either the right paratracheal area (60%), left paratracheal area (36.7%), or right lateral posterior lobe area not adjacent to the trachea (3.3%). Only a quarter of the patients had imaging findings suggestive of extrathyroidal extension and only 30% had clinically apparent vocal paresis/paralysis on preoperative examination. Invasion of the RLN was not observed for primary tumors <0.9 cm in diameter, regardless of tumor location. Conclusions: Well-differentiated PTC tumors ≥0.9 cm in maximal diameter that are located in the right paratracheal, left paratracheal, and right lateral posterior lobe subcapsular positions are usually not appropriate for active surveillance even in the absence of definitive evidence for nerve invasion on preoperative imaging or vocal cord examination. Patient selection for active surveillance management should take into account not only the size and growth rate of a tumor but also its location in relation to the expected course of RLNs. [ABSTRACT FROM AUTHOR]