Staging of Thyroid Cancer

Staging is the process of finding out if, and how far, a cancer has spread. It is also important to an individual patient to assess the relative risk of recurrence of the cancer in the future, which is discussed below.

The stage of a cancer is one of the most important factors in choosing treatment options and predicting the chance for cure. Most thyroid cancers present in the early stages, where the prognosis is excellent.

Various staging systems exist, designed to allow a standard way of summarising how an individual patient's cancer has developed and how far it has spread. This also allows better statistical analysis and allows researchers to compare similar groups when performing cancer treatment studies. The most common system used to describe the stages of thyroid cancer is the American Joint Committee on Cancer (AJCC) TNM system. 

The TNM staging system

The TNM system is based on 3 key pieces of information:

  • T indicates the size of the main (primary) tumour and whether it has grown into surrounding areas.
  • N describes the extent of spread to nearby (regional) lymph glands or nodes. Cells from thyroid cancers can travel to lymph nodes in the neck and chest areas.
  • M indicates whether the cancer has spread (metastasised) to other organs of the body. The most common sites of spread of thyroid cancer are the lungs, the liver, and bones.

Numbers or letters appear after T, N, and M to provide more details about each of these factors. The numbers 0 through 4 indicate increasing severity. The letter X means a category can’t be assessed because the information is not available.

T categories for thyroid cancer (other than anaplastic thyroid cancer)

TX: Primary tumour cannot be assessed

T0: No evidence of primary tumour

T1: The tumour is 2 cm across or less and is limited to the thyroid 

T1a: The tumour is 1 cm across or less and is limited to the thyroid

T1b: The tumour is between 1 and 2 cm across and is limited to the thyroid

T2: The tumour is more than 2 cm but not larger than 4 cm across and is limited to the thyroid

T3: The tumour is larger than 4 cm across and limited to the thyroid, or has minimal extrathyroidal extension

T4a: Moderately advanced disease; tumour of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, oesophagus, or recurrent laryngeal nerve

T4b: Very advanced disease; tumour invades prevertebral fascia or encases carotid artery or mediastinal vessel

T categories for anaplastic thyroid cancer

All anaplastic thyroid cancers are considered T4 tumours at the time of diagnosis.

T4a: The tumour is still within the thyroid

T4b: The tumour has grown outside the thyroid

N categories for thyroid cancer

Regional lymph nodes include the central compartment, lateral cervical, and upper mediastinal lymph nodes

NX: Regional lymph nodes cannot be assessed

N0: The cancer has not spread to regional lymph nodes

N1: The cancer has spread to regional lymph nodes

N1a: The cancer has spread to Level VI lymph nodes (pretracheal, paratracheal, and prelaryngeal lymph nodes)

N1b: The cancer has spread to other lymph node levels: unilateral, bilateral, or contralateral cervical (levels I, II, III, IV, or V) or retropharyngeal or superior mediastinal lymph nodes (level VII)

M categories for thyroid cancer

M0: There is no distant metastasis

M1: The cancer has spread to other parts of the body, such as distant lymph nodes, internal organs, bones, etc.

Stage Groupings

Once the values for T, N, and M are determined, they are combined into stages, expressed as a Roman numeral from I through IV, which gives a better picture of the likely outcome for an individual patient. Sometimes letters are used to further divide a stage.

Unlike most other cancers, the thyroid cancer groupings are also subdivided to take into account the type of cancer and the patient’s age:

Papillary or follicular (differentiated) thyroid cancer in patients younger than 45 years

Younger people have a low likelihood of dying from differentiated (papillary or follicular) thyroid cancer. The TNM stage groupings for these cancers take this fact into account. So, all people younger than 45 years with these cancers are stage I if they have no distant spread and stage II if they have distant spread.

Stage I = any T, any N, M0

Stage II = any T, any N, M1

Papillary or follicular (differentiated) thyroid cancer in patients 45 years and older

Stage I = T1, N0, M0

Stage II = T2, N0, M0

Stage III: One of the following applies:

T3, N0, M0

T1 to T3, N1a, M0

Stage IVA: One of the following applies:

T1 to T3, N1b, M0

T4a, any N, M0

Stage IVB = T4b, any N, M0

Stage IVC = any T, any N, M1

Medullary thyroid cancer

Age is not a factor in the stage of medullary thyroid cancer.

Stage I = T1, N0, M0

Stage II: One of the following applies: 

T2, N0, M0

T3, N0, M0 

Stage III = T1 to T3, N1a, M0

Stage IVA: One of the following applies:

T1 to T3, N1b, M0

T4a, any N, M0

Stage IVB = T4b, any N, M0

Stage IVC = any T, any N, M1

Anaplastic (undifferentiated) thyroid cancer

All anaplastic thyroid cancers are considered stage IV, reflecting the poor prognosis of this type of cancer.

Stage IVA = T4a, any N, M0

Stage IVB = T4b, any N, M0

Stage IVC = any T, any N, M1

 

Risk of Recurrence

Most patients also want an assessment of their risk of the thyroid cancer coming back, or recurring, and this is done by classifying patients into risk groups depending on the type of cancer, the findings of any staging investigations, and once removed, the pathological characteristics, which are determined by the pathologist assessing the tumour under the microscope.

Fig. 1: Risk of structural disease recurrence in patients without structurally identifiable disease after initial therapy (Source: ATA Guidelines 2015). The risk of structural disease recurrence associated with selected clinico-pathological features are shown as a continuum of risk with percentages (FTC, follicular thyroid cancer; FV, follicular variant; LN, lymph node; PTMC, papillary thyroid microcarcinoma; PTC, papillary thyroid cancer, ETE, extrathyroidal extension)

Low Risk

  • classical papillary cancer (PTC), without aggressive histology
  • no local (lymph node) or distant metastases
  • complete resection
  • no extrathyroidal extension (ETE) (spread locally outside the thyroid itself)
  • no vascular invasion
  • no radioiodine (RAI) uptake outside the thyroid bed 
  • clinically N0 or < or =5 pathological N1 micrometastases (<0.2 cm in largest dimension)
  • intrathyroidal, encapsulated follicular variant of PTC
  • intrathyroidal, well differentiated follicular thyroid cancer (FTC) with capsular invasion and no or minimal (<4 foci) vascular invasion
  • intrathyroidal, papillary microcarcinoma, unifocal or multifocal, including BRAFV600E mutations

Intermediate Risk

  • aggressive histology
  • vascular invasion
  • microscopic extrathyroidal extension (ETE)
  • RAI-avid metastatic foci in the neck on the first post-treatment whole-body RAI scan
  • clinically N1 or >5 pathologic N1 with all involved lymph nodes <3 cm in largest dimension
  • multifocal papillary microcarcinoma with ETE and BRAFV600E mutated (if known)

High Risk

  • incomplete tumour resection
  • macroscopic extrathyroidal extension (ETE)
  • distant metastases
  • inappropriate postoperative thyroglobulin elevation suggestive of distant metastases
  • clinically N1 with any metastatic lymph node > or =3 cm in largest dimension
  • follicular thyroid cancer with extensive vascular invasion (> 4 foci of vascular invasion)