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In oncology, “to stage” a patients malignant disease implies two intentions: (1) the use of clinical examination and investigations to describe the extent of disease to permit a rational treatment strategy to be formulated, (2) by employing an agreed classification system to categorise the extent of disease within risk hierarchies that predict the outcome following conventional treatment strategies [14].

The T (Tumour), N (Nodes) M (Metastasis) classification of malignant tumours was first proposed in 1944 by Pierre Denoix at Institute Gustav-Roussy, Paris, France [15]. Following incorporating the general definition of local extension of malignant tumours by the World Health Organisation, the first recommendations were published in 1958 by the Union for International Cancer Control (UICC) for the clinical stage classification of the breast and larynx [14], followed by that on cancer of the buccal cavity and pharynx in 1963. In 1968, a single booklet that contained 22 body site classifications was published and represented the first edition of the TNM staging system [16]. The American Joint Committee was founded in 1959 to complement the work in the United States; however, it was recognised that a single staging classification was desirable rather than competing classification and by 1980 strong collaboration both organisations (the American Joint Committee on Cancer (AJCC) renamed in 1980 and UICC) has continued since [16]. In the modern era, the 5th edition of TNM (1997), which contained rules of classification and staging that correspond exactly with those of the 5th edition of the AJCC, and that agreement has continued with the recent publication of the 8th edition of TNM (2017) of the AJCC and UICC [12, 13].

Fig. 2. T – Primary hypopharyngeal cancer.

Changes in the TNM tumour classification have occurred over time, and in the 5th Edition (1997), Stage IV hypopharyngeal cancer was composed of patients with advanced T4N0M0, patients who had extensive nodal disease (N2a or N3) and patients with evidence of metastatic disease (M1). In the 6th Edition (2002), this stage of disease was separated in Stage IVA (T1–3N2 and T4aN0–2), Stage IVB (T4b any N and any TN3) and Stage IVC (any T, any N, M1). Also, advanced T stage (T4) in the 5th Edition was a “mixed bag” encompassed by the term “tumour invades adjacent structures.” This advanced stage was separated into a and b, which was based on the involvement of vital structures (invasion of prevertebral fascia, encasing carotid artery, invasion of mediastinal structures). T4a implies locally advanced but resectable tumour, while T4b implies tumour that is not technically resectable but is suitable for non-surgical options. One obvious difficulty of using feasibility of surgical resection as a staging parameter is that it is subject to the availability of the level of available expertise. “Unresectability” is an emotive topic and when defined implies that surgical resection is either technically not feasible with a curative intent or not recommended by the surgical team [17]. The classification and staging of the TNM for hypopharyngeal cancer has remained unchanged from the 6th Edition (2002) up to the most recent 8th Edition (2017; Fig. 2–4) [18].

The N staging of hypopharyngeal cancer has been significantly changed from the 7th Edition 2009 with the recent 8th Edition 2017. The extranodal extension (ENE) has been added as a prognostic variable in addition to the number and size of metastatic lymph nodes. It has been recognised that imaging modalities have significant limitations and lack sensitivity and specificity in their ability to identify early or minor ENE. Therefore, for clinical staging, only unambiguous ENE, as determined by physical examination (e.g., invasion of skin, infiltration of musculature/dense tethering to adjacent structures, or dysfunction of a cranial nerve, brachial plexus, the sympathetic trunk, or the phrenic nerve) and supported by radiological evidence, should be present to assign a status of ENE-positive. Pathological ENE is defined as extension of metastatic carcinoma from within a lymph node through the fibrous capsule and into the surrounding connective tissue, regardless of the presence of stroma reaction. Metastatic carcinoma that stretches the capsule but does not breach it does not constitute ENE. The current validation of the stage grouping has been based on the management of oral cavity data, on the assumption that cancers of the larynx, hypopharynx and paranasal sinuses are high-risk HPV negative or, when positive, tend to behave similarly to their negative counterparts. This unproven assumption because of a lack of availability of data for the other studied sites, resulting that the changes to the N categories for all sites have been changed based upon the data from oral cavity sites [18].

Fig. 3. N – Regional lymph nodes.

A review of the SEER data between the years 1988 and 2003 reported the rate of distant metastatic tumour (M+), for tumours of the hypopharynx at diagnosis was 6.17% representing the highest risk among all sites evaluated, and the presence of a distant metastasis was more likely to be present with the increasing N and T stage of disease [19]. In hypopharyngeal cancer, the most important predictive tumour outcome factors are advanced T- and N-classification, loco-regional control (margin status) and histological grade [20, 21]. Presently there is no evidence that currently available biomarkers have any predictive role in determining the occurrence of distant metastases [22].

Most patients when diagnosed have advanced stage disease (stage III/IV), approximately 70–85% and of these 60–75% will have clinically apparent cervical regional lymph nodes (N1–3), and 20% will have contralateral occult cervical nodal metastasis (N2c) [23, 24]. Other local anatomic areas of possible lymph node metastasis that requires special attention include the retropharyngeal, parapharyngeal, paratracheal and mediastinal areas [25, 26].

Fig. 4. Stage groupings.