1. Treatment principles

The treatment of DTC is mainly surgical treatment, supplemented by postoperative endocrine therapy, radionuclide therapy, and in some cases, radiation therapy and targeted therapy. MTC is mainly surgical treatment, supplemented by radiation therapy and targeted therapy in some cases. In the treatment of undifferentiated cancer, a few patients have the opportunity to have surgery, and some patients may have some effect with radiotherapy and chemotherapy, but overall the prognosis is very poor and survival time is short. It is also important to note that individualization of tumor treatment is important, as each patient’s condition and complaints are different, and clinical diagnosis and treatment have some flexibility.

2. Surgical treatment of differentiated thyroid cancer

(1) Management of the primary focus:

For lesions with T1 or T2 tumor grade, which are mostly confined to one glandular lobe, resection of the affected glandular lobe and isthmus is recommended. For some patients with high-risk factors, total thyroidectomy is also feasible. These risk factors include multifocal cancer, lymph node metastases, distant metastases, family history, and early childhood exposure to ionizing radiation. Total thyroidectomy is also feasible in some cases where postoperative nuclear therapy is considered necessary. For tumors located in the isthmus, enlarged isthmus resection is feasible for small tumors, while total thyroidectomy can be considered for larger tumors or those with lymph node metastases.
Some of the T1 lesions are low-risk micro papillary carcinomas. Because of its relatively slow progression and low mortality rate, in addition to surgical treatment, conservative therapy can also be considered, i.e., active monitoring and close follow-up measures. The low-risk micro papillary carcinoma that can be closely monitored generally has the following characteristics: (i) the primary tumor is a single lesion, (ii) the maximum diameter of the primary lesion <1cm, (iii) the location of the primary lesion is located in the central part of the thyroid gland, rather than immediately adjacent to the thyroid peritoneum or trachea, and (iv) no regional lymph node metastasis is yet manifested after evaluation. In addition to the above conditions, specific factors such as the patient’s history of exposure to high doses of ionizing radiation during early childhood, family history of thyroid cancer, and the presence of combined hyperthyroidism should be taken into account. If close observation measures are taken, re-evaluation every 6 months is generally required.
If the evaluation reveals progression of the primary tumor (e.g., 2-3 mm increase in diameter, new tumor lesions, or clinically suspicious metastatic regional lymph nodes), discontinuation of conservative treatment measures and surgical treatment should be considered.
For T3 lesions with large tumors or tumors that have invaded the extraperitoneal muscles of the thyroid, total thyroidectomy is recommended. However, for lesions closer to the thyroid peritoneum, which may not be large per se but have invaded the extraperitoneal muscles, excision of the affected lobe and isthmus, together with excision of the invaded muscles, may be performed. T4a lesions require resection of part of the larynx (or even the whole larynx), part of the trachea, hypopharynx, and part of the esophagus, as well as the preparation of a repair plan. T4b lesions are generally considered non-operable, but the opportunity for surgery is determined on a case-by-case basis and may require multidisciplinary collaboration between vascular surgery, orthopedics, neurosurgery, etc. In general, however, T4b lesions are difficult to completely resect, have a poor prognosis, are associated with higher surgical risks, and have more postoperative complications. The decision to treat surgically requires careful evaluation of the condition, with a focus on whether the patient can benefit from surgery. Sometimes, palliative decompression therapy is necessary.
For example, tracheotomy to relieve dyspnea.

(2) Management of regional lymph nodes:

Central zone lymph nodes (zone VI): cN1a The central zone on the affected side should be cleared. If the lesion is on one side, it is recommended to include the affected tracheoesophageal groove and anterior trachea. The anterior laryngeal region is also part of the central zone clearance, but metastases to the anterior laryngeal lymph nodes are uncommon and can be treated individually. For patients with cN0, central zone clearance may be considered if there are high-risk factors (e.g., T3 to T4 lesions, multifocal carcinoma, family history, history of early childhood ionizing radiation exposure, etc.). For low-risk patients with cN0 (without high-risk factors), the treatment can be individualized. The extent of central zone clearance is defined as the level of the superior border of the innominate artery at the inferior border, the level of the hyoid bone at the superior border, and the medial border of the common carotid artery at the lateral border, including the anterior trachea. The right tracheoesophageal sulcus requires attention to the lymphatic fatty tissue at the deep level where the recurrent laryngeal nerve is located. The central region needs to be cleared with attention to protecting the laryngeal recurrent nerve, while protecting the parathyroid glands and their blood supply as much as possible, and if the parathyroid glands cannot be preserved in situ, parathyroid autotransplantation should be performed. Lateral cervical lymph node dissection (Zone I-V): Lateral cervical lymph node metastasis is most commonly seen in Zone III and IV, followed by Zone II and V. Zone I is less common. Lateral cervical lymph node dissection is recommended to be performed therapeutically, i.e. when N1b is confirmed by preoperative evaluation or intraoperative freezing. The recommended scope of lateral neck dissection includes zones II, III, IV, and VB, with zones IIA, III, and IV being the smallest. Zone I does not require routine clearance. The schematic diagram of the neck partition and the specific division of each zone are shown in Figure 1 and Table 8.
Lymph nodes in specific areas, such as parapharyngeal lymph nodes and upper mediastinal lymph nodes, are recommended for surgical resection at the same time when metastasis is considered on imaging.

3. Surgical treatment of MTC

For MTC, total thyroidectomy is recommended. In the case of MTC diagnosed after lobectomy, total thyroidectomy is recommended as a supplement. In individual cases, sporadic microscopic foci of MTC found incidentally after lobectomy may also be considered for close observation.
MTC is more prone to cervical lymph node metastasis, and most patients have lymph node metastasis at the time of presentation, so resection of the primary site should be accompanied by cervical lymph node dissection (central or lateral cervical area), the extent of which should be determined by serum calcitonin levels in addition to clinical assessment.
Some MTCs are hereditary medullary carcinomas and can be diagnosed by detecting germline mutations in the RET gene (by genetic testing of somatic cells or blood leukocytes). In this group of patients, total thyroidectomy and cervical lymph node dissection are recommended. In the case of MEN II patients, attention should be paid to the evaluation of the systemic situation. If there is a combination of pheochromocytoma, etc., it needs to be managed before considering thyroid surgery.

4. Surgical treatment of undifferentiated carcinoma

A small number of patients with undifferentiated carcinoma present with small tumors and may have surgical opportunities. Most patients with undifferentiated carcinoma have a large neck mass at the time of presentation and their disease is progressing rapidly, so there is no chance of surgery. Tracheotomy can be considered when the tumor compresses the trachea and causes respiratory distress.

5. Perioperative treatment

In addition to routine rehydration after thyroid cancer surgery, dexamethasone and neurotrophic drugs can be given as adjuvant therapy to reduce neuroedema. Patients with total thyroidectomy should review parathyroid hormone and blood calcium after surgery, and those with low calcium symptoms should pay attention to calcium supplementation and give oral vitamin D and calcium preparations as soon as they can eat. Patients with injury to one laryngeal nerve often choke on food and water during the acute phase. For some elderly patients, nasal feeding can be given if necessary to reduce the occurrence of aspiration pneumonia. If necessary, a tracheotomy kit is placed at the bedside for backup. Patients with bilateral recurrent laryngeal nerve injury usually undergo intraoperative tracheotomy with a tracheal tube, and postoperative care of the tracheotomy opening is noted. In patients with cervical lymph node dissection, postoperative attention should be paid to the functional exercise of the neck and shoulder. Postoperative adjuvant treatment plan should be formulated according to pathological staging and risk stratification, and patients should be informed.