Treatment of Thyroid Cancer: An Update from Dr Francis Hall

Thyroid Cancer Overview

Thyroid cancer accounts for 1% of all cancers in New Zealand. The incidence of thyroid cancer is 13 per 100,000 per year. About 1 in 100 people develop thyroid cancer over the course of their lifetime. It is three times more common in women.

There are four main types of thyroid cancer.

1. Papillary thyroid carcinoma is the most common type of thyroid cancer and has a tendency to spread to lymph nodes. With good treatment it has an excellent prognosis. There are several variants of papillary thyroid carcinoma (tall cell variant, columnar cell variant, hob nail variant, diffuse sclerosing variant, solid variant, TERT positive) that have a worse prognosis.
2. Follicular thyroid carcinoma is the second most common type of thyroid cancer and has a tendency for haematogenous spread to lungs, brain and bones. It also has an excellent prognosis.
3. Medullary thyroid carcinoma is less common. It sometimes runs in families and has an intermediate prognosis. Serum calcitonin is a very useful marker to help diagnose medullary thyroid carcinoma and to assess response to treatment.
4. Anaplastic thyroid carcinoma is a very aggressive thyroid carcinoma and has a very poor prognosis.

There are other types of thyroid cancer that are less common, including primary lymphoma of the thyroid, squamous cell carcinoma of the thyroid, etc.

The treatment of differentiated thyroid cancer

Differentiated thyroid carcinoma (DTC) is the term used to encompass both papillary thyroid carcinoma and follicular thyroid carcinoma. The American Thyroid Association (ATA)1 has guidelines on the treatment of differentiated thyroid carcinoma. In New Zealand, we generally follow the ATA guidelines. The ATA guidelines tend to be updated about every 5–10 years. The last ATA guidelines on the treatment of DTC were published in 2016. Updated ATA guidelines are expected this year.

The treatment of DTC usually involves one or more of the following:

1. Surgery
2. Radioactive iodine
3. Thyroxine

External beam radiotherapy is indicated for some distant metastases and in anaplastic thyroid carcinoma. Targeted agents are used in some patients with distant metastases.

The 2009 ATA guidelines on the treatment of DTC divided patients with DTC into a three-tiered risk system: low risk, intermediate risk and high risk. In the 2015 guidelines, this three-tiered risk system was further described as a continuum of risk. Patients with DTC are discussed at a thyroid multidisciplinary meeting and treatment recommendations are made. Twenty years ago, nearly all patients with DTC were treated with total thyroidectomy, radioactive iodine (RAI) and a suppressive dose of thyroxine. Nowadays, treatment of DTC is more selective and is guided by the level of risk. Many patients are now treated with hemithyroidectomy and without either RAI or a suppressive dose of thyroxine. Of course, patients treated with a hemithyroidectomy avoid the need to take thyroxine and the potential complication of hypocalcaemia.

The extent of surgery is determined by the extent of the disease and pathology. Patients with multifocal cancer and patients with more aggressive thyroid cancers are treated with total thyroidectomy. Patients with DTC and involvement of cervical nodes require a neck dissection in addition to total thyroidectomy. Patients with DTC treated with total thyroidectomy need thyroid hormone replacement therapy (thyroxine). The dose of thyroxine is monitored with serial TSH and fT4 measurement. The target level of TSH is determined by
the risk stratification of the patient and is usually determined by the patient’s endocrinologist. The target TSH level for the lowest risk patients is between 0.5–2.0mU/L (low end of normal range), intermediate risk patient (0.1–0.5mU/L) and for the highest risk patients is <0.1mU/L. A suppressive dose of thyroxine inhibits thyroid cell growth. A suppressive dose of thyroxine is associated with an increased (3.5x) risk of osteoporosis, hypertension, cardiac arrhythmias and ischaemic heart disease.

Patients with DTC are followed clinically and with ultrasound. Patients with DTC treated with total thyroidectomy are also followed with serum thyroglobulin and anti-thyroglobulin antibodies. Thyroglobulin is a marker of thyroid tissue. Both benign and malignant thyroid cells secrete thyroglobulin. The thyroglobulin level is interpreted in conjunction with the TSH level (stimulated or unstimulated thyroglobulin level). An undetectable stimulated thyroglobulin level combined with a low level of anti-thyroglobulin antibodies is associated with an excellent prognosis. With good treatment, patients with DTC usually have an excellent prognosis.

Papillary thyroid microcarcinoma

Papillary thyroid microcarcinoma is defined as a papillary thyroid carcinoma measuring 1cm or less. Treatment of this entity is controversial. Many advocate active surveillance with serial ultrasound. Some advocate hemithyroidectomy and others advocate radiofrequency ablation.

Non-invasive follicular thyroid neoplasm with papillary like nuclear features (NIFTP)

NIFTP is a new name for a very low-risk thyroid tumour previously known as encapsulated non-invasive follicular variant papillary thyroid carcinoma. It is best regarded as benign.

Medullary thyroid carcinoma

The ATA has separate guidelines for the treatment of medullary thyroid carcinoma. Patients with medullary thyroid carcinoma are generally treated with total thyroidectomy and central neck dissection plus or minus lateral neck dissection. In addition to clinical and radiological follow up, serial calcitonin measurement is an important part of their follow-up regime. Usually, medullary carcinoma has a less favourable prognosis than DTC.

Anaplastic thyroid carcinoma

Finally, the ATA has separate guidelines for the treatment of anaplastic thyroid carcinoma. It has the least favourable prognosis of the four main types of thyroid carcinoma, with very few people achieving long-term survival. Surgery is indicated only if complete resection is possible with minimal morbidity. Debulking procedures are not recommended. Treatment is mainly with chemotherapy and radiotherapy.

Take home points

1. The treatment of papillary and follicular thyroid cancer has become more selective, with low-risk patients now being treated with hemithyroidectomy alone.
2. Nowadays radioactive iodine is used less often than before in the treatment of thyroid cancer. RAI is reserved for patients with high-risk thyroid cancer and in some patients with intermediate risk thyroid cancer. It is not used in low-risk thyroid cancer.
3. The dose of thyroxine is determined by the target TSH range. The TSH range is determined by risk stratification of the patient: low, intermediate and high risk.