The management of thyroid cancer is highly dependent on the histopathological subtype as well as the stage of disease.
Management of Well-Differentiated Thyroid Cancers (Follicular / Papillary)
Surgery is the primary modality for the management of thyroid cancer.
- Total thyroidectomy is the default treatment
- Hemithyroidectomy may be performed for well lateralised tumours < 1 cm
- Wide local excision is required when large tumours invade adjacent structures
- Neck dissection is not required unless there is macroscopic nodal involvement
Primary radiotherapy is used for inoperable cases, although this is rare. A potentially curative dose is 66 Gy to the macroscopic disease and 50 Gy to 'at risk' sites.
Adjuvant Therapy
Radioiodine
Radioiodine (131I) is the 'silver bullet' for differentiated thyroid cancers (as well as for nuclear medicine imaging). It is administered for all patients with disease outside the thyroid (N1 or M1), as well as for tumours over 4 cm. For patients with tumours between 1 and 4 cm, 131I is used when high risk features are present (eg. lymphovascular invasion). Tumours under 1 cm have a very low risk of distant disease and observation is usual.
Administration of 131I occurs by:
- Cessation of thyroxine. This results in rising TSH levels which stimulates iodine uptake by malignant cells. Thyroxine is usually ceased for about 3 weeks and this must be done with care in elderly patients.
- Avoidance of iodine rich foods. This results in the radioiodine being taken up preferentially (instead of normal iodine).
The dose of 131I varies by department; doses range from 1 - 3 MBq in most instances; higher doses are often used for higher risk disease (stage IV).
Thyroxine
Thyroxine suppresses the production of TSH and is a useful tool in otherwise untreatable differentiated thyroid cancer, which is often driven by an abundance of TSH.
Radiotherapy
Adjuvant external beam radiotherapy is rarely used for well differentiated thyroid cancer. It is useful for several scenarios:
- When there is macroscopic residual disease
- When there is high risk of local recurrence - usually patients with T4 disease and microscopic positive margins and/or high risk features (insular pattern)
- When there is extracapsular extension from involved lymph nodes
These situations are rare in the modern setting. Typical dose is 50 Gy to subclinical disease and 66 Gy to macroscopic or microscopic residual disease.
Cytotoxic therapy
There is minimal role for cytotoxic therapy for well differentiated thyroid cancer.
Targeted therapy
The development of vascular endothelial growth factor receptor tyrosine kinase inhibitors (sunitinib, sorafenib) has allowed some role for systemic therapy aside from radioiodine. They have been shown in phase II trials to delay progression. They remain the source of significant interest for clinical trials.
Management of Medullary Thyroid Cancer
Medullary thryoid cancers are neuroendocrine tumours of the thyroid that are frequently active, producing calcitonin. They are frequently involve the entire thyroid gland and level VI lymph nodes, making resection of both mandantory.
- Unresectable tumours are usually treated with a dose of 50 Gy to macroscopic disease and 40 Gy to subclinical disease
- Adjuvant radioiodine or thyroxine therapy to suppress TSH is not indicated as the tumour does not concentrate iodine or respond to TSH
- Adjuvant radiotherapy is rarely recommended except in cases of gross or microscopic residual disease
- Advanced disease is best treated with VEGF/MET inhibitor vandetanib; sunitinib or sorafenib may do if vandetanib is unavailable.
ESSENTIAL: Medullary thyroid cancer is a hallmark of the Multiple Endocrine Neoplasia type 2 syndrome (MEN2), along with parathyroid tumour and phaeochromocytoma. A number of patients without a family history of MEN2 with medullary thyroid cancer may have a germline mutation in the RET gene; this places them at high risk of further disease if the thyroid is not completely removed. Patients also require screening for phaeochromocytoma.
Prophylactic Thyroidectomy for MET2
Guidelines for prophylactic thyroidectomy are based off the location of the mutation within the RET gene. Those with high risk mutations require thyroidectomy by age 1. The lowest risk mutations can avoid thyroidectomy until age 10. Thyroidectomy is associated with significant comorbidites for children.
Management of Anaplastic Thyroid Cancer
Anaplastic thyroid cancer is rapidly progressive with one of the worst prognoses among solid malignancies. Median survival is 3 months even with treatment. Almost all patients present with disease outside the thyroid gland (> 95%). Death occurs due to disseminated disease or due to local airway obstruction or invasion of nearby neck vessels.
In the rare event the tumour is localised to the thyroid, surgical excision followed by adjuvant radiotherapy is indicated - the recommended dose is 60 Gy in 40 #, with 2 # delivered per day (at least 6 hours apart). This is the only tumour I have seen this schedule for. Some centres use taxanes in conjuction with radiotherapy but this is not universal.
Most patients will be treated completely palliatively with 20 Gy in 5 fractions.
