Staging of Oral Cavity Cancer
TNM Classification System (AJCC 8th Edition)
The AJCC 8th edition TNM staging system is the current standard for oral cavity cancer, with two critical additions: depth of invasion (DOI) for T classification and extranodal extension (ENE) for N classification, which significantly improve prognostic accuracy compared to the 7th edition. 1, 2, 3
Primary Tumor (T) Classification
The T classification incorporates both tumor size and depth of invasion 1:
- T1: Tumor ≤2 cm with DOI ≤5 mm 1
- T2: Tumor ≤2 cm with DOI >5 mm and ≤10 mm, OR tumor >2 cm but ≤4 cm with DOI ≤10 mm 1
- T3: Tumor >2 cm with DOI >10 mm, OR tumor >4 cm with DOI ≤10 mm 1
- T4a: Moderately advanced disease with invasion of adjacent structures (cortical bone, deep extrinsic tongue muscles, maxillary sinus, facial skin) 1
- T4b: Very advanced disease with invasion of masticator space, pterygoid plates, skull base, or encasement of internal carotid artery 1
Critical point: DOI must be measured histopathologically from the level of the basement membrane of adjacent normal mucosa to the deepest point of tumor invasion—this is distinct from tumor thickness 2, 3. Clinical DOI (cDOI) assessed on imaging upstages approximately 14% of cases and improves prognostic discrimination 3.
Regional Lymph Node (N) Classification
The N classification now incorporates ENE as a critical upstaging feature 1, 2:
- N0: No regional lymph node metastasis 1
- N1: Single ipsilateral lymph node ≤3 cm without ENE 1
- N2a: Single ipsilateral lymph node >3 cm but ≤6 cm without ENE 4
- N2b: Multiple ipsilateral lymph nodes, none >6 cm without ENE 1
- N2c: Bilateral or contralateral lymph nodes, none >6 cm without ENE 1
- N3a: Any lymph node >6 cm without ENE 1
- N3b: Any lymph node with clinical ENE 1, 2
Critical point: The number of metastatic lymph nodes is a powerful independent prognostic factor that eclipses nodal size and laterality—mortality risk escalates continuously with each additional positive node, most pronounced up to 4 nodes 5. ENE presence increases mortality risk by 41% 5.
Stage Grouping
- Stage I: T1N0M0 1
- Stage II: T2N0M0 1
- Stage III: T3N0M0 or T1-3N1M0 1
- Stage IVA: T4aN0-2M0 or T1-4aN2M0 (moderately advanced) 1
- Stage IVB: Any T with N3, or T4b with any N (very advanced) 1
- Stage IVC: Any T, any N, M1 (distant metastatic) 1
Imaging for Staging
Primary Staging Modalities
Contrast-enhanced CT (CECT) of the neck is the primary imaging modality for oral cavity cancer staging, providing accurate assessment of tumor extent, DOI (for lesions >5 mm), osseous involvement, and regional nodal disease. 6
- CECT neck with IV contrast: Usually appropriate for initial staging, accurately estimates DOI and tumor thickness comparable to MRI for lesions >5 mm 6
- MRI neck without and with IV contrast: Usually appropriate, particularly superior for soft tissue delineation and perineural invasion assessment 6
- FDG-PET/CT skull base to mid-thigh: Recommended for stage III-IV disease to detect distant metastases and synchronous tumors, but insufficient alone for detailed anatomic staging 6
Critical imaging technique: The puffed-cheek maneuver during CT examination separates tumor from normal mucosa, providing clearer delineation of oral cavity tumors, particularly along gingiva and buccal mucosa 6.
Staging Accuracy and Pitfalls
Clinical staging yields approximately 82.5% diagnostic accuracy in predicting pathological tumor status 7. The main causes of understaging include:
- Surface dimension underestimation (62.5% of T upstaging cases) 7
- Deep invasion to tongue extrinsic muscles (37.5% of T upstaging cases) 7
- Occult nodal metastases: Single (57.6%) and multiple (42.4%) occult metastases account for N upstaging 7
Approximately 13-14% of cases are upstaged in T category, 4% in N category, and 13% in overall TNM stage when comparing clinical to pathological staging 7, 3.
Treatment Approach by Stage
Early-Stage Disease (Stage I-II: T1-2N0)
Single-modality treatment with surgery is the preferred approach for early-stage oral cavity cancer, as it provides similar locoregional control to radiotherapy while preserving the option for salvage radiotherapy if recurrence occurs. 6, 8
- Primary surgery: Conservative surgical resection is standard 6, 8
- Radiotherapy alternative: EBRT or brachytherapy for selected subsites, though based only on retrospective data 6
- Neck management: Ipsilateral selective neck dissection (bilateral for near-midline tumors) or sentinel node biopsy is recommended for cT1-2 tumors, except T1-2N0 glottic cancer 6
Critical decision point: Choice between surgery and radiotherapy should prioritize functional outcome and treatment morbidity for each patient, considering that surgery preserves radiotherapy as a salvage option 6, 8.
Locally Advanced Resectable Disease (Stage III-IVA: T3-4a or N+)
Primary surgical resection with appropriate reconstruction followed by risk-adapted adjuvant therapy is the standard treatment for resectable locally advanced oral cavity cancer. 8
Surgical Approach
- Wide surgical excision with appropriate reconstruction is mandatory for T3/T4 tumors 8
- Reconstruction: Free vascularized soft tissue flaps (radial forearm, anterolateral thigh) when mandibular continuity is intact; bony flaps (fibula) required if mandibular continuity is disrupted 8
- Neck dissection: Mandatory for all node-positive disease 8
- Minimum lymph node harvest: At least 10 lymph nodes should be examined, with survival improving up to 35 nodes examined 5
Adjuvant Therapy Decision Algorithm
High-risk pathologic features (require adjuvant chemoradiotherapy with cisplatin) 8:
- Positive surgical margins (R1 resection) 8
- Extracapsular extension in lymph nodes 8
- Regimen: 60-66 Gy at 2 Gy/fraction with concurrent cisplatin 8
Intermediate-risk features (require adjuvant radiotherapy alone) 8:
- Multiple positive lymph nodes without extracapsular extension 8
- Perineural invasion 8
- Lymphovascular invasion 8
- Close surgical margins 8
- Regimen: 56-60 Gy in standard fractionation 8
Evidence strength: Adjuvant CRT reduces risk of death by 16% compared to radiotherapy alone (HR 0.84,95% CI 0.72-0.98) 9. This represents moderate-certainty evidence from 1,097 participants across 4 studies 9.
Unresectable Disease (Stage IVB: T4b or Fixed Nodes)
Concurrent chemoradiotherapy with cisplatin is the standard treatment for unresectable oral cavity cancer, reducing the risk of death by more than 20% compared to radiotherapy alone. 8, 9
- Regimen: Concurrent cisplatin-based CRT with gross disease receiving 70 Gy in 2.0 Gy fractions and elective nodal regions receiving 44-64 Gy 8
- Evidence: CRT versus radiotherapy alone shows HR for death 0.74 (95% CI 0.67-0.83) from 2,852 participants across 24 studies 9
Critical point: Stage IVB disease without distant metastases does not automatically mean incurable disease—aggressive combined modality therapy can still be curative 1, 4.
Role of Induction Chemotherapy
There is insufficient evidence to support routine use of induction chemotherapy in oral cavity cancer, regardless of the regimen or subsequent treatment planned. 9
- Platinum plus 5-fluorouracil prior to radiotherapy: HR 0.85 (95% CI 0.70-1.04, P=0.11)—no clear survival benefit 9
- Cisplatin plus 5-fluorouracil plus docetaxel prior to CRT: HR 1.08 (95% CI 0.80-1.44, P=0.63)—no survival benefit 9
- Prior to surgery: HR 1.06 (95% CI 0.71-1.60, P=0.77)—no survival benefit 9
Essential Supportive Care Measures
Nutritional assessment is mandatory before treatment initiation 8:
- Patients with >10% weight loss in 6 months require enteral feeding before treatment 8
- Percutaneous gastrostomy is preferred over nasogastric tube for long-term support 8
Dental evaluation and rehabilitation are essential before radiotherapy to prevent osteoradionecrosis 8.
Pathologic Assessment Requirements
The pathology report must document 8: