If a person is suspected to have testicular cancer due to the presence of signs and symptoms, certain investigations are required to confirm the diagnosis of the disease and determining the stage of the disease, which in turn helps in choosing an appropriate treatment option.
The thyroid cancer treatment depends on many factors including the type of thyroid cancer, stage, age, and performance status of the patient, along with other factors.
Treatment for different types and stages of thyroid cancer
Stage I-II DTCs
Stage I-II DTCs are generally treated with surgery (lobectomy or total thyroidectomy) with or without radioiodine therapy (depending on the size of tumor and extent of invasion) as the standard treatment.
Stage III DTCs
Stage III DTCs are generally treated with surgery (total thyroidectomy) along with radioiodine therapy (if the disease is iodine-sensitive) or external beam radiation therapy (EBRT) as the standard treatment.
Stage IV DTCs
Stage IV DTCs sensitive to iodine are generally treated with radioiodine therapy as the standard treatment.
Stage IV DTCs that are not sensitive to iodine therapy can be treated with thyroid-suppression therapy, targeted therapy, or EBRT as per physician’s discretion. Surgery and EBRT may also be employed for palliation of symptoms of advanced disease.
Stage I-II MTCs
Stage I-II MTCs are generally treated with surgery (total thyroidectomy) with or without EBRT as the standard treatment.
Stage III-IV MTCs
Stage III-IV MTCs are generally treated with surgery (total thyroidectomy) along with thyroid hormone therapy and EBRT or targeted therapy as the standard treatment.
Palliative chemotherapy may also be employed for palliation of symptoms of advanced disease.
Genetic testing is generally recommended in MTCs so that other family members can also be screened and treated, as appropriate.
Stage IV Anaplastic thyroid cancer
Anaplastic thyroid cancers are generally already widespread at the time of diagnosis. Rarely, when the disease is confined to locoregional area, surgery (total thyroidectomy) to remove the thyroid and regional lymph nodes can be performed.
For extensive disease, EBRT and/or chemotherapy are generally employed as standard treatment.
Overview of Thyroid Cancer Treatment options
Surgery is the treatment of choice for most early-stage DTCs and MRCs and some cases of anaplastic thyroid cancers that have not spread to distant body parts and can be completely removed by a surgical procedure.
The main objective of surgery is to remove the primary tumor tissue along with some affected lymph nodes (if detected by imaging tests or during the procedure). Following are some commonly employed surgical procedures for the treatment of thyroid cancer:
Lobectomy: In this surgical procedure, only the affected lobe of the thyroid gland is removed (generally along with the isthmus). This surgery is usually employed for low-risk, small DTCs (<1 cm) confined to one lobe of the thyroid gland without any lymph node involvement.
The advantage of this procedure is that the patient can retain one lobe of the thyroid gland and will not require thyroid hormone supplementation after surgery. Radioiodine therapy cannot be given after this surgery as most of the iodine will be absorbed by the remnant thyroid.
Total Thyroidectomy: In this surgical procedure, the entire thyroid gland is removed. Some of the suspected lymph nodes may also be removed during this procedure, especially in case of medullary or anaplastic thyroid cancers.
Since all of the thyroid tissue is removed, thyroid supplementation is required after this surgery. The advantage of this procedure is that radioiodine therapy can be employed for ablation of any remaining (or recurrent) disease.
Surgery for thyroid cancer may be associated with the risk of complications, such as temporary or permanent hoarseness or loss of voice, damage to the parathyroid glands leading to low blood calcium level and associated symptoms, infection, excessive bleeding, blood clots in the neck, etc.
Radioiodine (RAI) Therapy
In this technique, the therapeutic dose of radioiodine I-131 (much higher than that used for radioiodine scan) is administered to the patient. The iodine is taken up by the thyroid cancer cells (including the normal cells if any).
The radiation from the iodine can destroy the thyroid cells that have concentrated the radioiodine, without much effect on the nearby healthy cells. This treatment is usually employed for destroying any remaining thyroid cells after total thyroidectomy or iodine-sensitive advanced-stage disease.
The radioiodine therapy can only work in the presence of a sufficiently high level of TSH, which is achieved by the administration of thyrotropin. Radioiodine therapy may be associated with side-effects like nausea, vomiting, swelling or tenderness in the neck or salivary glands, dry mouth, low sperm count in males, and irregularity in menstrual cycles in females.
Thyroid Hormone Therapy
This treatment approach includes taking thyroid hormones at slightly higher dose than normal daily after surgical removal of the thyroid gland. This serves two purposes, first it provides necessary thyroid hormone supplementation for maintaining body’s normal metabolism, and secondly, it helps in reducing the growth of any remaining/recurrent thyroid cancer cells by decreasing the TSH level in blood.
It can also be combined with other treatment modalities such as EBRT or chemotherapy for the treatment of some locally advanced or metastatic thyroid cancers. Side-effects of prolonged thyroid hormone therapy may include rapid or irregular heartbeat and osteoporosis.
External Beam Radiation Therapy (EBRT)
Radiation therapy uses high-energy x-rays or other high-energy radiations which are directed to the affected area to kill cancerous cells. EBRT is generally used when radioiodine therapy cannot be used for the treatment, for example, in the case of MTCs, anaplastic thyroid cancers, and iodine resistant advanced stage DTCs. Sometimes, EBRT is used as palliative therapy to relieve pain, bleeding, and obstructive symptoms associated with the advanced-stage disease.
Targeted drugs are designed to target a specific gene or protein characteristic of the thyroid cancer cells.
Following is the list of various targeted drugs that are currently approved or have shown potential for the treatment of thyroid cancer:
Lenvatinib is an orally active, small-molecule inhibitor of vascular endothelial growth factor receptor (VEGFR) 1 to 3, platelet-derived growth factor receptor (PDGFR) alpha, RET, stem cell factor receptor (KIT) and fibroblast growth factor receptor (FGFR) 1 to 4 kinases.
These kinases have been implicated to promote angiogenesis, growth, and progression of thyroid cancer cells. Lenvatinib is the preferred targeted agent and has been approved by US FDA for the treatment of patients with locally recurrent or metastatic, progressive differentiated thyroid cancer (DTC [including papillary, follicular, and poorly differentiated subtypes]) that is not responding to radioactive iodine treatment. It has been reported that patients whose tumors contain a RAS mutation have significantly better clinical outcome compared to those who lack this mutation.
Sorafenib is an orally active, small-molecule inhibitor of multiple kinases including VEGFR 1 to 3, PDGFR beta, KIT, RET/PTC, and less potently, BRAF. Sorafenib has been approved by the US FDA for the treatment of patients with locally recurrent or metastatic, progressive Differentiated Thyroid Cancer that is not responding to radioactive iodine treatment. It has been reported that the presence/absence of a BRAF or RAS mutation is not predictive of clinical outcome.
Sunitinib is an orally active, small-molecule inhibitor of multiple kinases including PDGFR alpha, PDGFR beta, VEGFR 1 to 3, KIT, RET/PTC subtypes 1 and 3, and others. Various clinical trials have shown the efficacy of sunitinib in the treatment of patients with MTC. Although not approved for the treatment of DTC, it can be used in the case of progressive and/or symptomatic metastatic disease when no appropriate clinical trial or preferred TKI agents are available.
Pazopanib is an orally active, small-molecule inhibitor of multiple kinases including VEGFR 1 to 3, PDGFR alpha and beta, and KIT; but it does not have significant inhibitory activity against the RET, RET/PTC, or BRAF kinases. Thus, it seems to exert its anti-thyroid cancer effect primarily via inhibiting the formation of new blood vessels. Similar to sunitinib, it can be used in the case of progressive and/or symptomatic metastatic disease when no appropriate clinical trial or preferred TKI agents are available.
Vandetanib is an orally active, small-molecule inhibitor of multiple kinases including VEGFR, RET/PTC, epidermal growth factor receptor (EGFR), and others. It is considered the preferred treatment option and has been approved by US FDA for patients with unresectable, locally advanced or metastatic MTC that is either symptomatic or progressive. It helps in controlling the progression of cancer; however, overall survival advantage is not yet proved in the clinical trials.
Cabozantinib is an orally active, small-molecule inhibitor that targets VEGFR 1 to 3, RET/PTC, KIT, c-MET and others. Similar to vandetanib, it is considered the preferred treatment option and has been approved by US FDA for patients with unresectable, locally advanced or metastatic Medullary Thyroid Cancer that is either symptomatic or progressive. Cabozantinib can also be employed for the treatment of patients with radioiodine-refractory DTC who have progressed on previous anti-VEGFR therapy.
Efatutazone is an orally active agonist of peroxisome proliferator-activated (PPAR)-gamma receptor. In combination with paclitaxel (chemotherapeutic drug), it could be helpful in the treatment of patients with advanced-stage Anaplastic Thyroid Cancer unresponsive to standard therapy.
Dabrafenib & Trametinib combination treatment
Dabrafenib is a BRAF kinase inhibitor and Trametinib is a mitogen-activated extracellular signal-regulated kinase (MEK)-1 and -2 inhibitor. ATCs frequently have mutations in the BRAF V600E gene and other mutations that lead to the activation of the mitogen-activated protein kinase (MAPK) and other proteins. These proteins promote cellular growth and proliferation. The combination of dabrafenib and Trametinib has been approved by US FDA for the treatment of patients with locally advanced or metastatic ATC that possess BRAF V600E mutation and for whom no other satisfactory locoregional treatment is currently available.
Selumetinib is an orally active, small-molecule, selective inhibitor of MEK 1 and MEK 2. It has been reported to increase the radio-iodine uptake by thyroid cancer cells. Thus, it is deemed to be efficacious in the treatment of patients with radioiodine-refractory thyroid cancer. Mainly, patients with NRAS mutation positive thyroid cancer were reported to derive the benefit of selumetinib treatment.
Vemurafenib is an orally active, small-molecule, selective inhibitor of BRAF serine-threonine kinase including BRAF V600E and other kinases that are involved in abnormal cellular proliferation and metastasis. It has shown some activity for the treatment of patients with progressive radioiodine-refractory BRAF V600-mutant thyroid cancer who have previously received treatment with antiangiogenic kinase inhibitors including sorafenib. Patients with any component of squamous differentiation within the primary or secondary papillary thyroid cancer lesion may confront disease progression with this drug. Thus, caution should be taken in such patients.
Chemotherapy means treatment with anti-cancer drugs that kill or decrease the growth of rapidly-growing cancer cells. Chemotherapy may be employed for the treatment of anaplastic thyroid cancers or for some advanced-stage MTCs that has spread to distant body parts. Depending on the physician’s preference and patient’s condition, it may also be combined with EBRT to accelerate the benefit achievement.
It may be associated with side effects like nausea/vomiting, hair loss, fatigue, cytopenias, etc due to its effect on normal body cells apart from cancerous cells.
This may help in improving the overall quality of life by providing relief from the symptoms caused by the thyroid cancer. They are generally given as supportive care for advanced stage cancer. These include but are not limited to using drugs to reduce pain and other symptoms such as vomiting, fatigue or external-beam radiation therapy for bleeding or pain, etc.
It is very important to assess the benefits of each treatment option versus the possible risks and side effects before making a treatment decision. Sometimes patient’s choice and health condition are also important to make a treatment choice.
Following are ultimate goals of treating thyroid cancer:
- Prolongation of life
- Reduction of symptoms
- Improvement of overall quality of life
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