What is the recommended approach for staging and treating oral cavity cancer?

Oral Cavity Cancer Staging and Treatment

For oral cavity cancer staging, perform clinical examination with rigid endoscopy under general anesthesia, contrast-enhanced CT and/or MRI of the head and neck to assess depth of invasion (DOI), and chest imaging with CT and/or FDG-PET to evaluate for distant metastases, followed by pathological confirmation via biopsy. 1

Initial Staging Workup

Mandatory Components

• Clinical examination with rigid head and neck endoscopy under general anesthesia is required for all patients to visualize the primary tumor and assess extent 1

• Contrast-enhanced CT and/or MRI of the head and neck must be performed to evaluate:

  • Primary tumor extent and margins 1
  • Depth of invasion (DOI), which is critical for oral cavity staging and determines neck management 1
  • Mandibular involvement, particularly important for oral cavity cancers 1
  • Regional lymph node involvement at levels I-III (primary drainage pattern) 1

• Chest imaging with CT and/or FDG-PET is necessary to detect distant metastases, particularly in patients with neck adenopathies or heavy smoking history 1

• Pathological confirmation via biopsy is mandatory before initiating treatment 1

Imaging Modality Selection

Contrast-enhanced CT is preferred for oral cavity cancers because it provides accurate estimation of DOI and tumor thickness in lesions >5 mm, performs similarly to MRI for this purpose, and offers excellent delineation of osseous anatomy including mandibular involvement 1. The puffed-cheek technique during CT examination allows better separation of tumor from normal mucosa, particularly for gingival and buccal lesions 1.

FDG-PET/CT should be added for stage III/IV disease as it may alter management by upstaging patients and detecting synchronous tumors or distant metastases 1. However, PET/CT alone is insufficient for initial staging as it lacks the anatomic detail needed for T-staging 1.

Pre-Treatment Risk Assessment

Beyond anatomic staging, every patient requires comprehensive evaluation of:

• Nutritional status with weight assessment - if weight loss exceeds 10% in the 6 months before diagnosis, enteral nutrition via percutaneous gastrostomy should be initiated before starting treatment 1, 2

• Dental examination with rehabilitation planning if radiotherapy is anticipated 1, 2

• Cardiopulmonary and renal function evaluation 1, 2

• Performance status and comorbidity assessment including frailty index for geriatric patients 1

• Speech and swallowing function baseline 2

Pathological Assessment Requirements

On surgical specimens, the following must be evaluated as they determine pathological staging, prognosis, and adjuvant treatment decisions 1:

• Tumor size and growth pattern 2
• Depth of invasion (DOI) - critical for oral cavity staging 1, 2
• Total number of lymph nodes removed and number involved 1, 2
• Presence of extracapsular extension 1, 2
• Perineural and lymphatic infiltration 1, 2
• Surgical margin status (R0, R1, or R2) 1, 2

The number of metastatic lymph nodes is a critical predictor of mortality, with risk escalating continuously with increasing nodes, most pronounced up to four nodes 3. This numerical burden eclipses other features like node size and contralaterality in prognostic value 3.

Treatment Approach by Stage

Early-Stage Disease (T1-2 N0)

Surgery is the primary treatment modality for early-stage oral cavity cancer 1, 2. Most experts prefer surgical therapy for resectable oral cavity tumors because functional outcomes after primary surgical management are often good with modern microvascular reconstruction techniques 1.

• Wide local excision with 1 cm clinical margins achieving ≥5 mm pathologic clearance when possible 2

• Neck management is determined by DOI 1, 2:

  • DOI <5 mm and cT1N0: active surveillance of the neck is acceptable 1, 2
  • DOI <10 mm: sentinel lymph node biopsy is a valid option 1, 2
  • For well-lateralized tongue tumors: ipsilateral selective neck dissection (levels I-IV) 2

• Alternative: External beam radiotherapy or brachytherapy can be used for selected stage I subsites, though this is based on retrospective data only 1, 2

Locally Advanced Disease (T3-4a or N+)

Surgery followed by risk-adapted adjuvant therapy is the standard approach 1, 2:

• Postoperative chemoradiotherapy (preferred, category 1) for adverse pathologic features:

  • Extracapsular nodal spread 1
  • Positive mucosal margins 1

• Postoperative radiotherapy or chemoradiotherapy for other risk features (clinical judgment required):

  • pT3 or pT4 primary 1
  • N2 or N3 nodal disease 1
  • Nodal disease in levels IV or V 1
  • Perineural invasion or vascular tumor embolism 1

Timing is critical: Postoperative radiotherapy or chemoradiotherapy must begin within 6-7 weeks of surgery, with the entire treatment sequence completed within 11 weeks, as treatment delays negatively impact local control 1, 2.

Unresectable Disease (T4b or Unresectable Nodes)

Options include 1:

• Concurrent chemoradiotherapy (T and N) 1
• Induction chemotherapy followed by RT or CRT for responders 1
• Palliative treatment: systemic chemotherapy/immunotherapy and/or palliative RT 1

Note: There is insufficient evidence to clearly demonstrate survival benefit from induction chemotherapy with platinum plus 5-fluorouracil prior to radiotherapy, surgery, or concurrent chemoradiation 4. Primary treatment with concurrent chemoradiotherapy, as compared to radiotherapy alone, reduces the risk of death by more than 20% 4.

Recurrent and Metastatic Disease

Treatment depends on prior therapy and PD-L1 status, which should be evaluated by an approved test 1, 2:

• For PD-L1-positive tumors: Pembrolizumab monotherapy with median overall survival of 12.3-14.9 months 2
• For PD-L1-negative tumors: Pembrolizumab plus platinum/5-FU with median overall survival of 13 months 2
• Locoregional recurrence: Referral to tertiary center for multidisciplinary evaluation of salvage surgery or re-irradiation 2

Surveillance Protocol

• Clinical examination with flexible endoscopy every 2-3 months for the first 2 years 2
• Baseline post-treatment imaging at 3 months for locally advanced disease 2
• FDG-PET/CT at 3 months post-chemoradiotherapy to assess need for neck dissection 2
• TSH levels every 6-12 months following neck irradiation 2
• Dental evaluation every 6 months for patients who received radiotherapy 2
• Tobacco and alcohol cessation counseling 2

Common Pitfalls

The 8th edition UICC TNM staging incorporates DOI as a critical prognostic factor for oral cavity cancer 1. However, TNM staging is a prognostic tool and current treatment strategies should not be modified based solely on new classifications 1. Treatment decisions must integrate both tumor parameters (location, histology, T stage, N stage) and patient parameters (physiological age, comorbidities, functional outcome expectations, personal preference) 1.

Regional node involvement at presentation occurs in approximately 30% of oral cavity cancer patients, but risk varies by subsite - alveolar ridge and hard palate infrequently involve the neck, whereas occult neck metastasis is common (50-60%) in anterior tongue cancers 1.