Thyroid cancer is generally divided into four pathological types: papillary, follicular, medullary and undifferentiated carcinomas. Papillary and follicular carcinomas, which account for the majority of thyroid cancers, are also called differentiated thyroid cancers because their cancerous tissues still retain the iodine uptake ability of normal thyroid cells. According to the possibility of tumor recurrence, differentiated thyroid cancer can be classified into low-risk and high-risk types. Age of onset <45 years, tumor diameter <1.0 cm, and no evidence of intra- and extra-thyroidal dissemination belong to the low-risk type (i.e. TNM stage I), which accounts for 85% of thyroid cancer.
Cases with TNM stage II, III and IV are high-risk type (TNM stage is a staging based on tumor size, surrounding lymph node involvement and distant metastasis). Unlike other tumors, differentiated thyroid cancer (DTC) and its metastases are sensitive to radioactive iodine (131I) treatment. The best treatment for differentiated thyroid cancer and its metastases is the “three-stage” treatment of thyroid surgery + radioactive iodine treatment + oral thyroid hormone.
I. Thyroid surgery.
It can provide diagnosis and staging, remove thyroid cancer, and prepare for radioactive ablation and serum thyroglobulin (Tg) monitoring. Surgical resection can be divided into total thyroidectomy, subtotal thyroidectomy and lobectomy depending on the type of cancer, tumor size, patient’s age and the presence of lymph node metastasis; if there is lymph node metastasis in the neck, total thyroidectomy and lymphatic dissection of the neck are required. At the time of diagnosis, 20% to 50% of papillary thyroid carcinoma has cervical lymph node metastasis. Therefore, during surgery, the lymph nodes in groups 4 and 5 of the neck are explored bilaterally, and the central group (group VI) lymph nodes should be removed even if there is no metastasis.
Expanding the scope of thyroid surgery can greatly improve the prognosis of high-risk patients, and even in low-risk patients, total or near-total thyroidectomy can greatly reduce the recurrence rate. Except for low-risk types with tumor diameter less than 1 cm and confined to the thyroid gland, total or near-total thyroidectomy should be performed. Inadequate excision of thyroid cancer not only increases the recurrence rate of thyroid cancer and shortens the survival period, but also causes difficulties in subsequent radioiodine (131I) treatment and monitoring during follow-up.
Therefore, it is important to have a thorough and complete first surgery. Complications that may occur after thyroid surgery include: unilateral or bilateral injury to the recurrent laryngeal nerve resulting in hoarseness; hypothyroidism, which usually requires lifelong thyroxine after surgery; or hypothyroidism of the parathyroid glands, which requires attention to blood calcium levels and timely calcium supplementation.
Second, postoperative radioactive iodine (131I) therapy consists of two levels.
First, 131I is used to remove residual thyroid tissue after DTC surgery, referred to as nail clearing; second, 131I is used to remove surgically unresectable DTC metastases, referred to as focal clearing. the significance of 131I nail clearing after DTC surgery is to reduce local recurrence and facilitate disease monitoring with radioactive iodine whole body scan or thyroglobulin (Tg) measurement after TSH stimulation during long-term follow-up. The use of this method has resulted in a significant reduction in disease recurrence and mortality. However, no benefit was seen in studies of low-risk papillary thyroid cancer in this area.
It is important to prepare before each 131I treatment by.
(1) Discontinue L-T4 for about 2-3 weeks to allow the body’s thyroid stimulating hormone (TSH) to rise above 30 mU/L. For the few who cannot tolerate thyroxine discontinuation, or whose TSH does not rise after thyroxine discontinuation, genetically recombinant human thyroid stimulating hormone (rhTSH) can be used before treatment, and this drug can be injected intramuscularly for two consecutive days before treatment to stimulate residual thyroid or thyroid tumor cells to take up radioactive iodine without thyroxine discontinuation (or just stop for four days).
(2) Low iodine diet (<50μg/day) for 1 to 2 weeks prior to 131I treatment.
(3) Pine 10mg/dose given routinely three times a day from 2 days before to 1 week after treatment. It can reduce the inflammatory swelling of the neck caused by radioiodine treatment.
(4) Radioactive iodine whole body scan (WBS) can be performed to find out whether there is any postoperative residual normal thyroid tissue and metastatic lesions that can take up iodine. When there is a large amount of residual normal thyroid tissue it can prevent 131I from showing lesions (e.g., lymph node metastatic lesions, lesions in the upper mediastinum or distant metastases). There is a growing body of research that discourages the use of radioactive iodine prior to ablation, primarily because of concerns that the 131I used in the scan may inhibit the uptake of 131I by subsequently treated thyroid cells.
Radioiodine is administered orally. In some patients (especially low- and intermediate-risk patients), lower doses (e.g., 30-75 mCi) can be effective, but the success rate of a single treatment session may be low. For medium- and high-risk DTC patients with both focal clearance purposes, the 131I dose for nail clearance treatment is 3.7-7.4 GBq (100-200 mCi).
Most of them are transient side effects, including mild swelling and pain in the salivary glands and mild dry mouth (caused by the uptake of radioactive iodine by the salivary glands), mild swelling of the neck (may be due to thyroiditis because of the large amount of existing thyroid tissue remaining at the time of surgery), and temporary hyperthyroidism. Since normal thyroid tissue is destroyed by radioactive iodine, it is necessary to take thyroxine replacement therapy for life.
If more thyroid tissue remains before the treatment, the start of L-T4 treatment may be delayed and the dose of L-T4 supplementation may be increased gradually because the 131I used for thyroid treatment destroys the thyroid tissue and releases thyroid hormones into the bloodstream to varying degrees.
The physician will schedule a 131I whole body scan 7 to 10 days after treatment to see if the cancer cells have metastasized to other sites. A whole-body scan after high-dose radioiodine treatment can detect an additional 10% to 26% of metastatic lesions compared to a diagnostic scan. Newly discovered lesions are mainly located in the neck, lungs and mediastinum. If there is still residual thyroid cancer tissue in the body or metastases from other sites, radioactive iodine treatment can be repeated, usually at intervals of 4-8 months between repeated 131I treatments, and if the tumor does not disappear completely, a second or third treatment can be performed.
131I clearance treatment is suitable for DTC metastases (including local lymph node metastases and distant metastases) that cannot be removed surgically but have iodine uptake function. The aim of treatment is to remove the lesion or partially relieve the disease. The first 131I focal clearance treatment should be performed at least 3 months after 131I nail clearance. Repeat focal clearance treatment should be performed at an interval of 4 to 8 months. The empirical dose of a single 131I focal clearance treatment is 3.7-7.4 GBq (100-200 mCi).
III. Thyroid hormone therapy.
Thyroid hormone therapy can suppress human serum thyrotropin, which can promote the growth of thyroid cancer cells. Therefore, thyroid hormone therapy can remove the environment that promotes the growth of thyroid cancer cells and achieve the purpose of treatment.
Significance of thyroid hormone therapy.
(1) Maintaining the normal function of the thyroid gland;
(2) Inhibit the secretion of thyroid stimulating hormone from the pituitary gland. Therefore, thyroid hormone replacement therapy is used for both total and partial thyroidectomy.
The side effects of thyroid hormone therapy are mainly manifestations related to subclinical hyperthyroidism, such as angina pectoris and atrial fibrillation in those with ischemic heart disease; and increased risk of osteoporosis in postmenopausal women. Therefore, TSH suppression therapy should be individualized, taking into account both the possible benefits and the potential risk of adverse effects.
IV. Follow-up review.
The goal of long-term follow-up for patients with differentiated thyroid cancer is to closely monitor patients with possible recurrence, and early detection of recurrent foci can help to implement effective treatment. Most recurrences occur 2 to 3 years after surgery. Local recurrence occurs in about 5% to 20% of differentiated thyroid cancers and distant metastases in 10% to 18%.
Ultrasound examination of the neck is highly sensitive to detect metastasis in the neck. Ultrasound examination of the neck should be performed at 6 and 12 months after treatment to assess the condition of the thyroid gland and bilateral cervical lymph nodes, after which the patient can be reviewed annually for at least 3-5 years depending on the serum Tg level and the risk of recurrence. Puncture biopsy and/or Tg testing of the puncture needle rinse may be performed on suspicious lymph nodes.
Diagnostic whole body radioiodine scan (DXWBS) should be performed 6 to 12 months after ablation therapy for high and intermediate risk patients with persistent tumors. In addition, all cancer patients should have an annual chest X-ray to check for lung metastases due to the low sensitivity of DXWBS after ablative therapy, and low-risk patients with undetectable Tg in TSH suppressed state and negative ultrasound.
Local metastatic lesions (enlarged cervical lymph nodes and soft tissue masses) found during follow-up should be surgically resected as a priority. For lesions that cannot be surgically removed or remain after surgery, those with positive DXWBS should be treated with radioiodine.
For multiple small nodular pulmonary metastases, 131I therapy should be continued as long as the metastases are able to uptake 131I, as these thyroid cancer patients are able to achieve complete clinical remission after treatment. Complete surgical resection of isolated bone metastases should be performed, which may lead to improved survival rates. Radioiodine, external X-ray irradiation and arterial embolization can be considered for unresectable bone metastases. Metastases in the central nervous system should be completely resected surgically regardless of the absorption of radioactive iodine, which can significantly prolong the survival time. If surgical resection is not possible, external irradiation should be performed.
For Tg-positive, 131I-negative, 18FDG-PET-positive lesions that cannot be surgically resected, a combination of L-T4 suppressive therapy, external irradiation therapy, and even chemotherapy with tyrosine kinase inhibitors may be tried. Those with stable disease may also be followed up closely only.
In patients with total or near-total thyroidectomy and thyroid ablation therapy, if there is no clinical manifestation of tumor, no imaging evidence of tumor, and no thyroglobulin measured in TsH suppression state or after stimulation, the tumor may be considered to be in complete remission.
Compared with other malignant tumors, thyroid cancer is relatively slow to develop malignancy. Even advanced differentiated thyroid cancer can still survive for a long time after appropriate surgical treatment, radiation therapy and endocrine therapy, and its 10-year survival rate can be as high as 80%. Therefore, there is no need to worry too much about thyroid cancer, as long as you maintain a positive and healthy attitude and choose the appropriate treatment, you can live and work like a healthy person. Generally speaking, the prognosis of thyroid cancer is good, for example, the twenty-year survival rate of papillary carcinoma can exceed 90; the ten-year survival rate of follicular carcinoma is about 80; the ten-year survival rate of medullary carcinoma is about 60 to 70; among them, only undifferentiated carcinoma has a higher mortality rate, and patients often die within a few months after the diagnosis is confirmed.