5 Evaluation and Staging for Cancers of the Oral Cavity
Summary
High-quality care for patients with oral cavity cancer requires comprehensive evaluation by a health care team experienced in the management of complex head and neck cancers. Assignment of disease stage must accurately reflect prognosis, guide management strategies, and allow comparison of like populations. The eighth edition of the American Joint Committee on Cancer (AJCC) staging system introduces major changes that incorporate emerging evidence in support of the prognostic value of depth of invasion of the primary lesion, and extranodal extension (ENE) in the setting of involved lymph nodes. Additionally, it clarifies the anatomical boundaries of the oral cavity for the purposes of stage assignment. This chapter highlights the key issues related to initial evaluation of patients affected by oral cavity carcinoma, and describes the hallmark changes introduced in the revised staging scheme for such malignancies.
5.1 Introduction
Accurate and reproducible staging information is a critical component of high-quality care for patients diagnosed with malignant neoplasms. In addition to providing information on prognosis and guidelines for management for individual patients, the stage assignment provides consistency in describing disease burden across care settings, and allows comparison of patient outcomes between centers and across time periods. Moreover, cataloguing of data on a well-defined and established set of rules permits evolution in understanding the disease process over time. The first American Joint Committee on Cancer (AJCC) cancer staging manual was published in 1977 to accomplish these goals. Since then, the manual has been updated at regular intervals to incorporate new data and better reflect the contemporary population and the prevalent understanding of malignant diseases.
The AJCC staging system for malignancies of the oral cavity utilizes the Tumor, Node, Metastasis (TNM) staging system, which was first described by Denoix in 1952, 1 and relies on anatomic extent of involvement with malignant disease. While this remains an accurate predictor of disease behavior, there has been recognition that other biologic factors may have a substantial role as well. The eighth edition of the AJCC Cancer Staging Manual, effective January 1, 2018, incorporates phenotypic variables that represent adverse biology and clinical behavior, such as ENE in involved lymph nodes and depth of invasion (DOI) at the primary site, in cancers of the oral cavity. While incorporating these important variables, the staging system aims to balance accuracy, ease of use, and universal applicability in settings with variable availability of resources. This chapter highlights the key changes in the eighth edition of the AJCC Cancer Staging Manual for malignancies of the oral cavity and the rationale in support of these changes.
5.2 Overview of Changes in the Eighth Edition of the AJCC Staging Manual
AJCC Cancer Staging System is revamped at regular intervals. Frequency of revisions must strike a balance between reflecting current data and staying relevant to current clinical practices, and the burdens experienced by physicians, patients, cancer registries, and the health care systems on account of introduction of new staging parameters. Presently, the staging systems are updated once every 7 or 8 years.
The eighth edition significantly updates the staging information for cancers of the oral cavity by incorporating depth of primary tumor invasion. Previously, extrinsic tongue muscular involvement served as the surrogate marker for DOI, and was the standard that contributed to assignment of more advanced T classification. However, pathologists and clinicians struggled with how best to capture this feature, resulting in inconsistent data collection. The more reproducible standard of DOI has been incorporated based on a growing body of data supporting its importance. 2 – 4 ENE has been added to the N classification to reflect the negative impact of this finding on prognosis and recurrence. 2 – 4 Another important change is reflected in the definition of the staging boundaries of the oral cavity. These changes will be discussed in detail in the following sections.
5.3 Anatomic Considerations for Cancers of the Oral Cavity
A clear definition of anatomical confines is a prerequisite for accurately choosing the correct staging system and stage assignment when evaluating patients with a newly diagnosed malignancy. Malignant tumors are staged according to the site of their origin. In circumstances where the tumor extends to adjacent sites, the clinician must determine the epicenter of the neoplasm based on clinical examination, imaging studies, and sometimes molecular markers, in order to use the appropriate staging scheme. For example, squamous cell carcinoma (SCC) centered on the inner mucosa of the lower lip that has minor extension onto the cutaneous surface of the lip should be classified using the staging system for oral cavity, and not cutaneous SCC. Conversely, a lesion that is at the vermilion border and predominantly on the dry mucosa of the lower lip should be staged using the cutaneous staging system (Chapter 14 of the eighth edition of the AJCC Cancer Staging Manual).
Importantly, the definition of the anterior staging boundary of the oral cavity has been revised with the eighth edition of the AJCC staging manual. Previously, the vermilion border defined the line of demarcation between oral cavity and cutaneous structures. Under the old schema, tumors of the dry portion of the vermilion lip would have been classified as lip tumors. However, the anterior boundary of the oral cavity has now been clarified as the location where the lips contact one another 2 (▶ Fig. 5.1). Any malignancy arising anterior to this wet-dry junction, even if it is located on the vermilion lip (red lip), should be classified as a cutaneous malignancy. Likewise, any malignancy arising from the wet lip, posterior to the wet-dry junction, should be classified as an oral cavity malignancy. This reclassification recognizes that tumors originating anterior to the contact point of the lips, even if they arise from the dry vermilion lip, share a common etiology with, and behave in a similar fashion to, cutaneous malignancies.
The posterior boundary of the oral cavity is located at its interface with the oropharynx. Superiorly, this is defined by the junction of the hard palate and the soft palate. Laterally, this is defined as the anterior faucial pillar. Inferiorly, the circumvallate papillae separate the oral tongue from the base of tongue (oropharyngeal tongue). This distinction now holds greater meaning, as oropharyngeal tumors may have a distinct etiology and biologic behavior with the rise of human papillomavirus (HPV) associated SCC in this region.
The most common location of regional nodal metastases from the oral cavity is to level I, II, and III cervical lymph node basins. Lungs are the most likely site of distant metastases, although bone, liver, and other soft-tissue sites may also be involved.
5.4 Evaluation
Workup of patients with known or suspected oral cavity malignancies should include a detailed history, physical examination, biopsy of primary or metastatic lesions, cross-sectional imaging studies, and an examination under anesthesia, as indicated.
Since the oral cavity can harbor a host of benign, premalignant, and malignant entities, clinicians should consider a wide differential when evaluating a patient with an oral lesion. While a full discussion on benign diseases of the oral cavity is beyond the scope of this book, details pertaining to premalignant lesions of the oral cavity are provided in Chapters 3 and 4.
5.4.1 History and Physical Examination
Clinicians should elucidate the duration of the lesion, its rate of growth, history of similar lesions in the past, associated lymphadenopathy, and symptoms associated with the presentation to hone the differential diagnosis. Patients may report symptoms such as ulceration, pain, foul breath, bleeding, dental loss, difficulty with chewing or swallowing, or symptoms suggestive of sensory, motor, and cranial nerve deficits. Concurrent oral health issues relevant to the workup of an oral cavity lesion include erosive lichen planus, history of recurrent aphthous stomatitis, Fanconi’s anemia, history of radiation, and a history of any prior head and neck malignancies.
Clinicians should consider the patient’s social history and role of the known risk factors for oral cavity malignancies, including smoking or chewing tobacco, alcohol use, betel nut chewing, and history of erosive lichen planus. 5 , 6 When applicable, the use of tobacco and alcohol should be quantified by pack-years and numbers of drinking days per week with number of drinks per day, respectively. A quit date, if present, should also be recorded.
Medical comorbidities should also be discussed, both in order to treat the patient as a whole and also to determine potential impact of baseline health on surgical risk, treatment options, and the survivorship experience. Medical conditions and their contribution to frailty is recognized as important risk factor for head and neck surgical patients. 7 , 8 Frailty can be estimated by a number of measures. The Modified Frailty Index is a measure of frailty that assesses 11 clinical variables and is represented as a score signifying degree of frailty. Another measure, the Johns Hopkins Frailty Index measures frailty as the presence of any one of a number of frailty-defining diagnoses, 7 grouped into 10 clusters, including malnutrition, dementia, severe vision impairment, decubitus ulcer, incontinence of urine, loss of weight, fecal incontinence, social support needs, difficulty in walking, and fall risk. While several other methods of measuring frailty have been tested, and validated, irrespective of the preferred tool, clinicians should consider frailty as an indicator of decline in physiologic reserve, which should be included as a key variable when formulating individualized treatment plans. Similarly, the presence of depression, anxiety, and other behavioral health issues or antidepressant use should be noted. The role of counseling and prophylactic use of antidepressants in reducing the incidence of major depression and their favorable impact on quality of life, especially in patients who require radiation therapy as part of their treatment, should be discussed and initiated when appropriate. 9 , 10
A focused, yet detailed, head and neck examination should be performed. The primary tumor should be inspected carefully, paying attention to the boundaries of the tumor with respect to anatomical subsites. The dimensions of the tumor should be measured in centimeters and clearly recorded. When possible, clinical images may be added to the patient’s medical record to facilitate objective record keeping of disease extent and collaboration with multiple specialties caring for the patient. The revised staging system makes it important to determine the tumor’s DOI in millimeters. It is important to distinguish DOI from “tumor thickness,” since DOI signifies the depth of tumor invasion into deep tissue and not the exophytic or heaped component of the tumor above the basement membrane. This distinction is discussed further below. It is readily acknowledged that exact determination of DOI may be clinically challenging, and may be further impacted by patient variables such as pain or trismus. However, clinicians should use their best clinical judgment in making a determination if the DOI for a particular oral malignant lesion is “thin” (= 5 mm), “intermediate” (> 5 mm but = 10 mm), or “thick” (> 10 mm). In cases of clinical uncertainty, the staging rules and convention call for assigning the lower category when assessing DOI.
The examination of the neck should include inspection and careful palpation. Any suspicious or enlarged lymph nodes should be evaluated for number, size, location, consistency, fixation to surrounding tissues, and overlying skin changes. A comprehensive cranial nerve examination, including, but not limited to, the lingual nerve, the inferior alveolar nerve, and the hypoglossal nerve, should be performed. Involvement of cranial nerves carries important staging, and therefore prognostic information, as neck node involvement of these structures increases the clinical N category to 3b.
Flexible fiberoptic nasopharyngolaryngoscopy may be utilized to evaluate the airway, to evaluate the base of the tongue, and to examine for the presence of possible synchronous, second primary malignancies.
5.4.2 Imaging Studies
Imaging studies should be utilized in select patients to evaluate the primary tumor, the status of the cervical lymph nodes, and, when appropriate, to evaluate for the presence of distant metastases.
It is important to note that imaging is not indicated for superficial, localized T1-T2 oral lesions, with no clinical lymphadenopathy. For lesions involving the alveolar ridge, which are not mobile over the bone, a dental panoramic radiograph, dental plain films, or computed tomography (CT) of the mandible may further clarify concerns over bone involvement. Contrast-enhanced CT scan or magnetic resonance imaging (MRI) may assist the evaluation of the primary lesion by providing additional information on tumor depth, and its relationship to adjoining structures, including the mandible, maxilla, skull base, major vascular structures, neural foramina, and, in the case of MRI, cranial nerves. Reliable assessment of the primary lesion may be hobbled in some cases due to its small size or superficial nature, and proximity to dental restorations, which may distort image quality.
Imaging of the neck may be indicated when there is clinical suspicion for regional lymph node involvement, need for assessment of regional anatomy for surgical planning, and when clinical examination fails to provide information that may inform management choices. Ultrasonography can be particularly useful in characterizing cervical lymph nodes. When available in the office, clinician-performed ultrasound can provide critical and complementary information about regional nodal status and facilitate guided aspiration of target lesions when indicated. In the presence of pathologic nodes, cross-sectional?imaging such as contrast-enhanced CT scan or MRI may help determine the size and number of nodes and help determine extent of surgery. While ENE may be suggested by imaging studies, radiological findings alone are not sufficient to satisfy the high bar set for clinical determination of ENE for staging purposes, and requires corroborating findings on clinical examination as described earlier in this chapter.
It is important to note that no imaging modality is sensitive enough to rule out the presence of occult cervical metastasis, 11 though CT scan may be more sensitive than MRI. 12 Therefore, when the risk of occult cervical metastasis is greater than 15 to 20%, 13 elective neck dissection is generally indicated. 14 – 16 Management of the neck nodes in oral malignancies is discussed further in Chapter 32.
To evaluate for distant metastases, cross-sectional imaging of the chest is warranted in patients with three or more clinically positive lymph nodes, low jugular lymph nodes, bilateral lymph nodes, lymph nodes sized = 6 cm, locoregional recurrence, and second primary tumors. 17 , 18 Localized (T1-T2, N0) oral cavity malignancies generally do not warrant cross-sectional imaging of the chest. 19
In some instances, imaging studies may reveal the presence of a single pulmonary nodule. 20 The presence of an incidentally discovered pulmonary nodule during workup warrants further evaluation and characterization with appropriately chosen radiographic modalities and a directed biopsy when indicated. Differential diagnoses including benign and malignant entities must be considered, before determining if the finding of the pulmonary nodule would in fact influence the management of the oral cavity malignancy. In a single-institution retrospective study of 148 consecutive patients with newly diagnosed head and neck cancer (not limited to the oral cavity), 73 (49.3%) of the patients had an abnormal chest scan on initial workup. Of these patients, 45 (61.7%) ultimately were identified to have intrathoracic lesions that were benign, 22 (30.1%) malignant, and 6 (8.2%) indeterminate. 21 Of nodules that were ultimately proved malignant, only three were initially characterized as benign. Multidisciplinary care teams must consider the appearance and number of such lesions, findings from previous imaging studies, risk factors for primary or metastatic pulmonary neoplasm, goals of care, and other patient factors when deciding on management for patients who present with pulmonary lesions discovered during the workup of an oral cavity malignancy.
Studies have compared the diagnostic accuracy of chest CT scan to positron emission tomography with CT (PET-CT) in evaluating for distant pulmonary metastases. Brouwer et al, based on several retrospective series, suggested that PET-CT may have a higher sensitivity for pulmonary metastases. 22 , 23 This was studied prospectively in a multi-institutional study of 145 consecutive patients who underwent both chest CT scan and PET-CT. 24 Distant metastases were identified in 19 patients (21%). Notably, the combination of chest CT scan with PET-CT was more accurate than either modality alone in the detection of distant metastases (positive predictive value, 86%; negative predictive value, 84%). Clinicians should consider patient care priorities and institutional protocols when choosing the appropriate imaging modality to assess for distant metastases.
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