TNM and Number Stages For Laryngeal Cancer

What is TNM classification for laryngeal cancer?

TNM Staging Laryngeal Cancer

The staging system denoted here as TNM staging for laryngeal cancer is a staging that originated from the American Joint Committee of Cancer (AJCC). It is utilized to quantify the cancer spread and the area affected using three variables.

• T – Size and extent of the primary tumor
• N – Spread to regional lymph nodes
• M – Presence of distant metastasis

Laryngeal carcinoma is classified into three regions;

• Supraglottis – area above the vocal cords
• Glottis – the vocal cords themselves
• Subglottis – area below the vocal cords

Laryngeal Cancer Staging System

Laryngeal cancer staging is done according to advanced AJCC TNM classification; however, there are slight differences in the staging based on the location within the larynx.

TNM Classification System

The ‘T’ category is based on the notion of primary tumor that refers to the initial or original cancerous growth of a specific tissue or organ based on its subsite.

Supraglottis

• T1 – Limited to one subsite, normal vocal cord mobility
• T2 – Extends to the mucosa of one or more regional sites adjacent to the primary site or to the glottis, and the vocal cords mobility is normal or only mildly impaired
• T3 – Vocal cord fixation or invasion of postcricoid area, pre-epiglottic space, inner thyroid cartilage
• T4a – Invades outer thyroid cartilage, trachea, soft tissues (neck)
• T4b – Invades prevertebral space, mediastinum, encases carotid artery

Glottis

• T1 – Vocal cords only (may involve anterior or posterior commissure), mobility normal.
• T1a – One vocal cord
• T1b – Both vocal cords
• T2 – Extension to supraglottis and/or subglottis, or impaired mobility
• T3 – Vocal cord fixation or paraglottic space invasion
• T4a – Invades thyroid cartilage, soft tissues
• T4b – Invades prevertebral space, mediastinum, encases carotid artery

Subglottis

• T1 – Limited to subglottis
• T2 – Extension to vocal cords with normal or impaired mobility
• T3 – Vocal cord fixation
• T4a – Invades thyroid cartilage, trachea, soft tissues
• T4b – Prevertebral space, mediastinum, or carotid artery invasion

N – Regional Lymph Nodes

• N0 – No regional lymph node metastasis
• N1 – Single ipsilateral lymph node ≤3 cm
• N2a – Single ipsilateral node >3 cm but ≤6 cm
• N2b – Multiple ipsilateral nodes ≤6 cm
• N2c – Bilateral/contralateral nodes ≤6 cm
• N3a – Node >6 cm
• N3b – Nodes with extranodal extension

M – Distant Metastasis

• M0 – No distant metastasis
• M1 – Distant metastasis present

Stage 1 Laryngeal Cancer Survival Rate

Laryngeal cancer in Stage 1 is normally diagnosed early and it is normally localized hence patients have high survival rate. Here's a general overview:

5-Year Relative Survival Rate:

~85% to 95%, depending on:

• Position or location of the tumor (glottic cancers are rather more favorable than those of the larynx at large).
• Patient's age and health
• Treatment modality (surgery vs. radiation)
• Timely evaluation of the new cases and treatment of the patients.

Stage 2 Laryngeal Cancer Treatment Options

Stage 2 laryngeal cancer is where the disease has progress to an extent that it has extended to more than one subsite or cord Fixation and changed the mobility or none spread to the lymph node or distant metastasis (T2 N0 M0). It is intended to treat cancer with the goal of overall voice preservation and preservation of swallowing depending on the site of tumor being glottic, supraglottic or subglottic.

Main Treatment Options

Radiation Therapy (RT) Alone

• Most common for glottic tumors
• Non-invasive, voice-preserving
• 5-year local control rates: ~70–90%
• Favored for the patients not suitable for surgeries

Surgery

Conservation (organ-preserving) surgery:

• Partial laryngectomy (open or transoral laser microsurgery)
• Supraglottic laryngectomy for supraglottic tumors
• Cordectomy or hemilaryngectomy for glottic tumors
• Voice may be changed, however the larynx may remain in tact
• May be preferred if patients do not respond to radiation therapy

Surgery + Radiation Therapy (Sequential)

• Alternatively, a tumour of a specific size might constitute a close or positive surgical margin.
• It is applied when there is either weak reaction or relapse after the initial therapy.

Stage 3 Laryngeal Cancer Prognosis

Laryngeal cancer at the stage 3 still means the extent of the tumor is as follows:

• More advanced locally (e.g., vocal cord fixation, invasion into nearby areas), OR
• There is tumour spread only to a single lymph node not more than 3 cm in diameter or there is no spread to other organs distant from the original site.

(T3 N0 M0 or T1–T3 N1 M0)

5-Year Relative Survival Rate

• Glottic ~60–70%
• Supraglottic    ~45–60%
• Subglottic    ~35–50%

Stage 4 Laryngeal Cancer Life Expectancy

The fourth stage of laryngeal cancer is the last one and it is subdivided into three stages with different outcomes.

Stage IVA

• Advanced stage; for example, the tumour abutting or invading adjacent structures similar to cartilage, soft tissues or invading multiple lymph nodes.
• No distant metastasis

5-Year Survival:

• Glottic    ~40–50%
• Supraglottic    ~30–40%
• Subglottic    ~25–35%

Stage IVB

• Very advanced such as tumor which encase the carotid artery or invade the mediastinum.
• More extensive nodal disease (e.g., N3 or extranodal extension)

5-Year Survival:

• The relapse lasts for 3–5 years, and the overall recurrence rate is estimated to be at 20–30% due to the effectiveness of therapy and other concurrent illnesses.

Stage IVC

• The far stage which involves formation of other tumors at a distance (such as lungs, liver, bones etc)

 Median Life Expectancy:

• Often 6–12 months without treatment
• May be increased to 12–24+ months with palliative cytochemotherapy, immunotherapy or chemotherapy with targeted agents in the selected individual
• Few patients have survival greater than five years, achieved good performance status and response to systemic therapy

Laryngeal Cancer Symptoms by Stage

First of all, the symptoms of laryngeal cancer depend on the tumor localization, it may be glottic, supraglottic or subglottic, as well as the stages of the disease. Early dysphagia result in voice disorders while late dysphagia and the presenting clinical syndromes are identified from swallowing, breathing difficulties and general symptoms.

Stage 0 (Carcinoma in Situ)

• Often asymptomatic
• This may be found occasionally during the examination period.
• Occasional hoarseness (especially if on vocal cords)

Stage I

Glottic (vocal cords):

• Persistent hoarseness (most common and early symptom)
• Mild voice changes

Supraglottic:

• Slight difficulty swallowing
• Sensation of a lump in the throat

Subglottic:

• It is quite infrequent; can result in cough or shortness of breath

Stage II

• Worsening hoarseness
• In more severe cases, the patient may present with ear pain syndrome referred as otalgia at interval, sore throat and headache while swallowing.
• Mild difficulty swallowing (dysphagia)
• The other symptoms are cough (dry or observing occasional hemoptysis).
• This has the implication that voice that is used frequently may become easily tired.

Stage III

• Vocal cord fixation → severe hoarseness or voice loss
• Painful swallowing    
• Ear pain on one side
• This is evidenced by the presence of a lump in the neck region due to lymph node involvement.
• Shortness of breath or noisy breathing (stridor)
• It is noteworthy that weight loss and fatigue may start

Stage IV

• Chronic dysphagia of at least degree of severity – the inability to swallow even liquids.
• Airway obstruction (may require tracheostomy)
• Persistent neck mass
• Chronic pain in throat or ear
• Visible tumor in throat (in advanced cases)
• Frequently distant symptoms: hemoptysis, bone ache, symptoms of anorexia if metastases exist.
• Weakness, fatigue, and cachexia

TNM System Head and Neck Cancer

TNM classification is used in staging the presence of cancer in different parts of the head and neck other than the brains and the eyes. It is used to assess the scope of cancer and its management and value in estimating outcomes. TNM stands for:

T – Size and extent of the primary tumor

N – Involvement of regional lymph nodes

M – Presence of distant metastasis

Early Stage Laryngeal Cancer Diagnosis

The diagnosis process of early-stage laryngeal cancer is carried through examination, investigation in form of imaging and taking tissues for biopsy. It is also a fact that, early diagnosis is good for prognostic and vocal quality conservation in patients with glottic tumors since it presents initial complaints such as voices.

Diagnostic Steps

History and Physical Exam

• Detailed ENT and systemic symptom review
• The collected risks factors are as follows: Smoking, alcoholic consumption, human papillomavirus, and family history.

Indirect Laryngoscopy / Flexible Fiberoptic Laryngoscopy

• Performed in-office by ENT
• This reflects vocal cords, supraglottis and subglottis.

Detects:

• White/red patches (leukoplakia/erythroplakia)
• Masses or vocal cord immobility
• Surface irregularities or thickening

Imaging 

CT scan or MRI of the neck:

• Evaluates tumor extent, cartilage invasion
• Assesses lymph nodes

Chest X-ray or CT chest:

• For this purpose, all patients belonging to high risk groups should be evaluated for lung metastasis or secondary tumours.

Biopsy

• Direct laryngoscopy under anaesthesia (gold standard for tissue diagnosis)
• Sample sent for histopathology
• Most common type: Squamous Cell Carcinoma (SCC)
• May also include molecular analysis such as HPV status and/or presence of oropharyngeal component.

Staging Workup

TNM staging based on:

• Tumor size/extent (T)
• Nodal spread (N)
• Metastasis (M)

Laryngeal Cancer Stages Explained

Treatment of laryngeal cancer depends on the stage of cancer – the more advanced, the greater the options for its removal. Staging is a way of categorizing the destructive potential of the cancerous cells based on tumor size and location (T), regional lymph nodes involvement (N) and the level of distant metastases (M). They are namely; stage 0 (in situ) to stage IV (advanced or metastatic).

Stage 0 – Carcinoma in Situ

• The cancer occurs on epithelial lining of the larynx and therefore the cancer cells do not invade deeper layers of the larynx.
• No invasion into deeper tissues.
• Often asymptomatic or mild hoarseness.
• Very high cure rate.

Stage I – Localized

• T1 refers to a small tumor that has not extended beyond the one sub-site of the larynx.
• Vocal cords are mobile; there is no enlargement of the lymph nodes or metastasis to distant sites.
• Symptoms: hoarseness, mild throat discomfort.
• Excellent prognosis with radiation or limited surgery.

Stage II 

• Tumor spreads to adjacent parts of the larynx.
• It may also impair the movement of pedal vocal cords but still only in the Larynx region.
• No lymph node involvement or distant spread.
• Treatment: radiation or partial laryngectomy.
• High cure rate with early treatment.

Stage III 

• The spread of the malignant cells to more localized areas or the lymph nodes.

Tumor:

• Fixes vocal cords, or
• Invades nearby areas, or
• Spreads to 1 lymph node ≤3 cm
• Symptoms: Main and possible symptoms include hoarseness, swallowing pains, a lump in the neck, and any signs of airway blockage.
• Treatment: often chemoradiation or surgery + radiation.
• Prognosis is still potentially curable.

Stage IVA – Moderately Advanced

Tumor invades:

• Thyroid cartilage
• Soft tissues of the neck (e.g., strap muscles)
• Multiple lymph nodes on same side
• Still no distant metastasis.
• Management: mainly total laryngectomy with concurrent chemoradiation.
• The survival rates of patients will therefore depend on their reaction to the treatment and their condition.

Stage IVB (advanced locally invasive cancer) 

Tumor:

• Encases carotid artery, or
• Invades prevertebral space, or
• Spreads to large or multiple lymph nodes
• Often non-resectable.
• Treatment: palliative chemoradiation or targeted therapy.
• Prognosis is guarded.

Stage IVC – Metastatic

• Metastases have developed to other areas of the body (organs, such as lungs, liver, bones).
• Signs and symptoms include: loss of weight, spitting of blood, bone aches, and recurring fatigue.
• Treatment: palliative care, chemotherapy, immunotherapy.
• Its concentration is on one the longevity and on the quality of the persons’ lives.

Advanced Laryngeal Cancer Treatment

Sets of Stages III and IV of laryngeal cancer referred to an advanced laryngeal cancer and include either of the following

• Large or deeply invasive tumors (T3–T4),
• Spread to neck lymph nodes (N1–N3),
• Or distant metastasis (M1 in Stage IVC).
• Management varies with the stage, site, general health of the patient, and if the goal is to save the voice box.

Stage III & IVA (Locally advanced but have not spread to other body parts)

Primary Treatment Approaches:

• Organ-Preserving Chemoradiation (CRT)
• Concurrent radiation + chemotherapy (e.g., cisplatin)
• Preserves voice in many cases
• It should be given when the tumor is resectable but organ-sparing can be done
• Should not be taken for those with kidney, liver, and bone marrow disease.

Surgery (Total or Partial Laryngectomy)

• Total laryngectomy if the tumour is bulky or persists after radiochemotherapy
• It may also involve the removal of the lymph nodes on the neck area.

However, if the following conditions are met; then postoperative radiation ± chemotherapy is prescribed:

• Margins are positive
• Extracapsular nodal spread exists

Induction Chemotherapy → CRT or Surgery

• Employed in a selective manner wherein some tumours are reduced in size before undergoing other forms of treatment.
• Decides on possibility of preserving the larynx

Stage IVB (Very Advanced Locally)

• Often unresectable tumors

Treatment goals:

• Symptom control
• Prolongation of survival
• Improved quality of life

Treatment Options:

• Palliative chemoradiation
• Targeted therapy (e.g., cetuximab) if not suitable for cisplatin
• Tracheostomy or gastrostomy may be required for purpose of providing an airway or nutrition support.

Stage IVC (Distant Metastasis)

Systemic and Palliative Approaches:

• Immunotherapy (e.g., pembrolizumab, nivolumab)
• Chemotherapy ± targeted therapy
• Ways to manage bleeding, pain, or obstructive airway through radiation
• Supportive care for nutrition, speech, and symptom management

Tumor Staging for Laryngeal Cancer

The T stage in laryngeal cancer (part of the TNM system) describes the size and extent of the primary tumor. 

• Glottis (vocal cords)
• Supraglottis (above vocal cords)
• Subglottis (below vocal cords)

Nodal Involvement in Laryngeal Cancer

The N stage of laryngeal cancer specifies whether the cancer has spread to the lymph nodes in the neck: the number of the nodes involved, size, position and if the cancer has extended beyond the capsule of nodes.

Metastasis in Laryngeal Cancer Stages

The M stage mainly relates to the distant metastasis, in which the cancer has moved out of the larynx and nearby lymph nodes to other sections of the body.