For metastatic differentiated thyroid cancer, radioactive iodine (131I) therapy can eradicate tumor cells and is highly effective. However, even with adequate thyroid stimulation and avoidance of excessive iodine intake, only 2/3 of patients with metastatic differentiated thyroid cancer can consume large amounts of iodine, with a cure rate of only 42%. Patients with ineffective radioiodine therapy have an expected survival of 3-5 years and lack of appropriate medication. Treatment was once hampered by the lack of consensus on the diagnosis and treatment of radioiodine-resistant differentiated thyroid cancer. For this reason, the expert group discussed the diagnosis and treatment modalities in September 2012. Patients with radioiodine-resistant differentiated thyroid cancer are broadly divided into the following four categories: 1. Patients with metastatic lesions without iodine uptake at the time of initial treatment The following patients cannot benefit from radioiodine therapy: clear lesions with no iodine uptake at the time of radioiodine whole-body scan; lesions with iodine uptake but cannot benefit after radioiodine therapy scan. 2.Patients with loss of iodine uptake before metastases This group of patients has multiple metastases, and the loss of iodine uptake may be due to the eradication of better differentiated cells with iodine uptake and the metastasis of poorly differentiated cancer cells with loss of iodine uptake. 3.Patients with some lesions with iodine uptake function and some without iodine uptake function Most commonly seen in patients with multiple metastases, which are usually defined by PET-CT scan or diagnostic whole-body CT scan with radioiodine as tracer by 124I, 18-FDG, and their metastases will have further loss of iodine uptake function (especially able to uptake 18-FDG), and they cannot benefit from radioiodine therapy. 4. Patients whose lesions have iodine uptake but whose metastases are further progressing The consensus clearly states that if the lesions are still deteriorating after adequate radioiodine treatment, continued treatment is ineffective. During radioiodine therapy, the tumor response is mainly observed by imaging (CT or MRI) and functional (lesion iodine uptake and serum thyroglobulin measurement). The assessment methods are diverse, but some differences may exist, such as when imaging shows a decrease in iodine uptake but an increase in serum thyroglobulin concentration, which requires a thorough evaluation of the condition. Some conditions are still unexplained, such as some patients whose metastases are all iodine uptake, but who are not cured after several radioiodine treatments (these patients also have no progression of the lesions according to RECIST criteria). This group of patients has a low probability of cure with continued radioiodine therapy and a progressive risk of side effects, such as secondary tumors and leukemia. Whether this group of patients (especially those who received 600 mCi) can be classified as radioiodine resistant and whether to discontinue radioiodine therapy is still controversial. Support for continuation of radioiodine therapy is based mainly on the response to the previous course of treatment: continued significant iodine uptake, reduced 18F-FDG uptake and few adverse effects. If PET-CT shows high 18F-FDG uptake in the lesion, the likelihood that radioiodine therapy will be fully effective is reduced; therefore, radioiodine therapy should be avoided if 18F-FDG uptake or enhanced function is found in the lesion. Finally, radioiodine therapy is usually not recommended for patients who cannot undergo thyroidectomy because the presence of the thyroid gland makes iodine uptake unassessable and radioiodine therapy ineffective, and such patients should be managed as radioiodine resistant. Once radioiodine therapy is completed, patients should be followed closely, primarily with 18F-FDG-PET CT or plain CT scans of the neck, chest, abdomen and pelvis. Follow-up intervals are determined according to disease progression. If the disease progresses, the follow-up interval is up to one year. The following indicators determine whether a patient undergoes systemic or clinical trial therapy: tumor size, disease progression, symptoms, and high risk of local complications. If a patient has multiple metastases larger than 1-2 cm and progression within 12 months, systemic therapy may be considered; conversely, if there are no metastases or metastases smaller than 1 cm and there is no evidence of progression, close follow-up is recommended. If the metastatic lesion is relatively large and has no iodine uptake, PET-CT shows uptake of 18F-FDG, and the disease does not progress, systemic therapy is recommended, but limited to frequent follow-up (imaging at least once every 2-3 months) is not feasible, or there is a high risk of complications. Based on the above consensus, we propose a management treatment process for patients with differentiated thyroid cancer with distant metastases (as shown in Figure 1). For this group of patients, appropriate methods are selected for local treatment (surgery, local external irradiation, thermal ablation) or radioiodine therapy, or both, provided that the lesions are iodine uptake. Once one or more lesions become non-iodine uptake or deteriorate further, the patient is defined as radioiodine resistant and radioiodine therapy is not recommended. If the metastases are large and continue to deteriorate, then systemic therapy is the treatment of choice.