What is thyroid cancer?

Thyroid cancer is a cancer of the thyroid gland, the butterfly-shaped gland in the front of the neck that produces hormones controlling metabolism. Most thyroid cancers are diagnosed when a thyroid nodule is found on physical examination or on imaging done for another reason. Many thyroid cancers grow slowly and have excellent outcomes with appropriate treatment.

The main types.

Differentiated thyroid cancer (DTC): the most common forms (papillary, follicular, Hurthle cell). They tend to grow slowly, often respond well to surgery and radioiodine, and have good long-term outcomes for most patients.

Medullary thyroid cancer (MTC): an uncommon type that arises from different cells in the thyroid (C cells). About a quarter of cases are inherited (most often from a RET gene mutation), and the rest are sporadic.

Anaplastic thyroid cancer (ATC): a rare and aggressive type that grows quickly and has historically had a poor outlook. Modern molecular targeting has substantially improved outcomes for the subset of ATC with targetable mutations.

Why molecular profile now matters. Modern thyroid cancer is no longer treated as one disease. Specific genetic features identify whether a particular targeted medicine is likely to work.

RET fusions or mutations: occur in many medullary thyroid cancers and a meaningful subset of differentiated thyroid cancers. RET inhibitors (selpercatinib, pralsetinib) are highly effective in RET-altered disease.

NTRK fusions: uncommon but actionable. NTRK inhibitors (larotrectinib, entrectinib) are tumour-agnostic options for NTRK-fusion-positive disease, including thyroid cancers.

BRAF V600E mutations: occur in a substantial fraction of papillary thyroid cancers and a subset of anaplastic thyroid cancers. Combination therapy with dabrafenib plus trametinib is highly effective in BRAF V600E-mutant anaplastic thyroid cancer specifically.

ALK and other rare alterations: each carries specific targeted therapy options.

The therapy approach.

Differentiated thyroid cancer: total thyroidectomy with central neck dissection in selected patients is the primary treatment. Radioiodine therapy is given to selected risk-stratified patients to ablate any remaining thyroid tissue and treat microscopic disease. Long-term levothyroxine therapy is used to replace thyroid hormone and (in selected patients) to keep TSH suppressed.

For radioiodine-refractory disease: lenvatinib and sorafenib are first-line systemic options. Targeted therapy based on molecular profile (RET, NTRK, BRAF V600E) is layered in based on identified alterations.

Medullary thyroid cancer: surgery is the primary treatment. Targeted therapy with RET inhibitors transforms outcomes in advanced RET-mutant disease.

Anaplastic thyroid cancer: rapid molecular profiling at diagnosis is essential because the tumour grows quickly and BRAF V600E-mutant disease responds dramatically to targeted therapy. Multimodal therapy combining targeted therapy, surgery, radiation, and chemotherapy is delivered at specialist centres.

What to expect. For most patients with differentiated thyroid cancer, modern treatment leads to excellent long-term outcomes. For patients with advanced or anaplastic disease, comprehensive molecular profiling is essential because the right targeted therapy can transform the outlook. Treatment at a centre with thyroid cancer expertise and access to comprehensive molecular profiling is the single most important factor for less common thyroid cancer presentations.