Depth of staging

October 15, 2018 0 By CH Unnikrishnan

The American Joint Committee on Cancer (AJCC), 8th Edition marks a major change in the Tumour Nodal Metastasis (TNM) staging of head_and_neck cancers. It introduces many new concepts to stage and prognosticate patients better, with distinct therapeutic implications.

In oral cancer, it introduces the depth of invasion as a determinant of T(tumour)_stage. This standardises the staging of oral cancer tumours and acknowledges the significance of depth of invasion in nodal spread and overall survival. It also eliminates “extrinsic muscle invasion” from stage T4 for oral tongue cancer; this was a constant source of confusion since the depth of invasion required to involve the extrinsic muscles of the tongue was highly variable depending on the position of the tumour in relation
to the tongue. Even very superficial tumours could invade the extrinsic muscles of the tongue. The nodal staging recommendations have also upstaged extranodal extension, which has been shown to be a high_risk adverse feature associated with worse survival.

In oropharyngeal cancer, human papillomavirus (HPV) expression of tumours has been used to reclassify tumours into two separate entities with distinct staging systems. For HPV_positive tumours (p16 positive), the T_stage no longer has T4b, or very advanced local disease, which represents the improved prognosis that these patients have when compared to their non_HPV counterparts. For HPV_positive tumours, nodal staging has been divided into clinical staging and pathological staging for better prognostication of HPV_positive diseases treated with surgery.

In carcinoma of unknown primaries with cervical nodal metastasis, immunohistochemical staining of nodal tissue for HPV and Epstein–Barr virus (EBV) has been recommended in all cases. This recognizes the high incidence of metastasis from an HPV_positive oropharyngeal or an EBV_positive nasopharyngeal primary tumour, and the need to standardize the diagnostic evaluation in these patients to avoid inadequate evaluation and inappropriate treatment.

These recommendations are based on high_quality evidence aimed at personalizing cancer therapy to optimize outcomes, while minimizing morbidity. The practice of oncology in India, however, is markedly different from that in the western world. India spends a small fraction (under 2%) of its gross domestic product on health_care services, with an estimated 65% of all healthcare_related expenditure being spent out_of_pocket. This results in a clear majority of patients with cancer receiving an insufficient quality and standard of care. This context of resource constraint has a significant impact on the practice of resource_heavy medical specialties such as oncology, where newer diagnostic and therapeutic techniques are often out of reach for many patients in developing countries.

Depth of invasion in oral cancers

Tumours having a depth of invasion of 5 mm or less are classified as T1, those having a depth of invasion 6–10 mm are classified as T2, and those with a depth of invasion higher than 10 mm and less than 20 mm are classified as T3. Tumours more than 20 mm depth or crossing the midline are T4b cancers. The subjectivity and interobserver variability in determining the clinical depth of invasion may be challenging. For those treated with surgery, the measurement of the depth of invasion is pathological, where a plumb line is dropped from the adjacent mucosa to the deepest point of tumour invasion. The issue with this parameter, as seen in other malignancies, is the interobserver variability; studies have shown a variable concordance rate among pathologists with respect to the depth of invasion.

A significant number of patients with oral cancer in India are treated with radiotherapy, either as brachytherapy or external beam radiotherapy. The measurement of the depth of invasion in these patients poses a bigger challenge, and there is no consensus on radiological determination of the depth of invasion in oral cancer.

Nodal staging in oropharyngeal cancer

For HPV_positive oropharyngeal cancer, clinical nodal staging is now similar to the nodal staging for nasopharyngeal cancer: N1 is one or more ipsilateral nodes with none >6 cm, N2 is contralateral or bilateral lymph nodes with none >6 cm, and N3 comprises nodal disease >6 cm. Pathological staging is N1 when metastasis occurs to ≤4 lymph nodes. N2 is when metastasis occurs to >4 lymph nodes. This is meant to better prognosticate HPV_related oropharyngeal cancers at two distinct points – with a clinical determination of staging at presentation, and a definitive pathological staging following surgery. This is most likely a reflection of the increasing use of transoral robotic surgery (TORS) in the treatment of oropharyngeal cancer in the United States.  Access to TORS, however, has been shown to correlate with socioeconomic status even in a developed country; and the number of patients with head_and_neck cancer in India with access to TORS is minuscule.

Unknown primary

For patients with squamous cell carcinoma demonstrated in cervical lymph nodes without any demonstrable primary site of malignancy, strong recommendations have been made regarding the addition of immunohistochemistry to the diagnostic evaluation. Acknowledging that around 90% of all unknown primaries are associated with an HPV_related oropharyngeal cancer in the United States, the AJCC has recommended that HPV in situ hybridization, p16 immunohistochemistry, and EBV_encoded RNA in situ hybridization be performed for all unknown primaries of the cervical lymph nodes. Whether this recommendation is feasible in an Indian context is debatable; the number of unknown primaries associated with HPV in India is likely to significantly fewer when compared to that of the West. The technical expertise and equipment required to perform routine immunohistochemistry and techniques such as in situ hybridization are also lacking in many centres that provide cancer care in India.

In short, the new recommendations made by the AJCC 8th Edition for the treatment of head_and_neck cancers address many of the shortcomings of the previous editions. The majority of these recommendations are universal. However, some are likely to face hurdles in their implementation in India. The recommendations represent a step toward standardization in radiological and pathological reporting. However, the degree of compliance that can be attained to these recommendations remains to be seen.