Oral Cancer: Stages and Treatment in Detail

Overview

Pathology and Grading

Staging (AJCC 8th Edition TNM)

1. Depth of invasion (DOI) now incorporated into T-staging
2. Extranodal extension (ENE) now upstages nodal disease

T (Primary Tumor) Classification

DOI is a pathologically determined feature from the surgical specimen; it can be estimated radiologically but is confirmed histologically. It has direct prognostic impact:

• DOI <2 mm: 13% regional metastasis rate, 95% 5-year survival
• DOI 2-9 mm: 46% regional metastasis, 85% 5-year survival
• DOI >9 mm: 65% regional metastasis, 65% 5-year survival

N (Regional Lymph Node) Classification

M (Distant Metastasis)

Overall Stage Grouping

Patterns of Lymph Node Metastasis by Subsite

Workup and Diagnosis

• Clinical examination: thorough systematic palpation and inspection of all subsites; leukoplakia and erythroplakia (5-7x higher malignant potential) require biopsy
• Imaging: CT and MRI are mandatory; CT is more sensitive/specific than panorex for mandibular invasion
• EUA (examination under anesthesia): for lesions not fully assessable in clinic
• Sentinel lymph node biopsy (SLNB): used in some centers for staging early (cN0) oral cancers; a positive SLNB prompts completion neck dissection

Treatment

Stage I and II (Early Disease - T1-T2, N0)

• Wide local excision with adequate margins is the standard of care for early oral cavity cancers
• Oral tongue: partial glossectomy; reconstruction with local flaps, primary closure, or regional flap depending on defect size
• Floor of mouth: transoral resection; marginal mandibulectomy considered when tumor is near periosteum
• Surgical margins: clear margins (typically ≥5 mm) are paramount; close or positive margins mandate re-excision or adjuvant radiation
• Neck: Elective neck dissection (END) is recommended when occult metastasis risk exceeds 20%. Selective neck dissection (SND) of levels I-III is standard for most oral cavity primaries

• Perineural invasion present
• Lymphovascular invasion
• Close surgical margins
• Multiple lymph nodes involved

Stage III (T3N0 or T1-T3 N1)

• More extensive resection required; mandibular involvement may require marginal or segmental mandibulectomy
• Neck dissection is routinely performed; SND levels I-III for most, extending to levels IV-V for advanced disease
• Adjuvant radiotherapy (60-66 Gy) with or without concurrent cisplatin-based chemotherapy, depending on pathological features
• Reconstruction with regional pedicled flaps (pectoralis major) or microvascular free flaps

Stage IVA (T4a, resectable)

• Composite resection may include segmental mandibulectomy, infrastructure or total maxillectomy
• Mandibular resection options:
  • Marginal mandibulectomy: periosteum involved but not cortical/medullary bone; removes superior alveolar rim
  • Segmental mandibulectomy: full-thickness bone removal; mandatory when medullary invasion present
• Reconstruction: microvascular free tissue transfer (e.g., fibula free flap for mandibular reconstruction, anterolateral thigh flap, radial forearm free flap) is the standard for large defects
• Adjuvant concurrent chemoradiation: cisplatin-based CRT is standard for:
  • Extranodal extension (ENE)
  • Positive surgical margins (that cannot be re-resected)
  • Multiple positive nodes

Stage IVB and IVC (Unresectable / Metastatic)

• Reserved for medically inoperable patients, T4b (unresectable) disease, or patient preference against surgery
• Radiation (IMRT preferred): 66-70 Gy to primary and involved nodes; 44-54 Gy to elective nodal volumes
  • IMRT (Intensity-Modulated Radiation Therapy) reduces xerostomia, osteoradionecrosis, and dysphagia compared to conventional techniques
• Concurrent chemotherapy: cisplatin 100 mg/m² every 3 weeks or weekly cisplatin is standard
• Organ preservation trials show similar survival outcomes compared to surgery + adjuvant therapy, but patients may experience greater toxicity from definitive (versus adjuvant) doses
• Chemotherapy is never used as a single agent for oral cavity cancer

• Platinum-based palliative chemotherapy (cisplatin + 5-FU ± cetuximab)
• Immunotherapy: pembrolizumab (anti-PD-1) is now approved for recurrent/metastatic HNC
• Goals shift to symptom control and quality of life

Adjuvant Therapy Indications (Post-Surgery)

Prognosis by Stage (Floor of Mouth as Example)

Treatment Side Effects and Complications

• Xerostomia (dry mouth): most common after radiation; worsened by bilateral parotid irradiation
• Osteoradionecrosis: bone necrosis after radiation, especially mandible; risk increased with high doses, dental disease, and smoking
• Dysphagia/trismus: from radiation fibrosis, tongue base involvement
• Dysgeusia: altered taste, often during/after radiation
• IMRT significantly reduces but does not eliminate these toxicities

Sources

• Sabiston Textbook of Surgery, 21st ed. - Oral Cavity Cancer
• Cummings Otolaryngology Head and Neck Surgery, 7th ed. - Staging and Surgical Treatment
• Bailey and Love's Short Practice of Surgery, 28th ed. - TNM Staging (AJCC 8th edition)
• Scott-Brown's Otorhinolaryngology Head & Neck Surgery - Cancer of the oral cavity