What is the treatment approach for oral squamous cell carcinoma of the tongue?

Treatment of Oral Squamous Cell Carcinoma of the Tongue

For oral tongue squamous cell carcinoma, primary surgical resection with neck dissection is the preferred treatment, followed by adjuvant radiotherapy or chemoradiotherapy based on pathologic risk factors. 1

Treatment Algorithm by Stage

Early Stage Disease (T1-2N0)

Single-modality treatment with surgery is the standard approach for early-stage oral tongue cancer. 1

• Perform wide local excision with adequate margins (minimum 5mm clear margins are crucial for survival). 2, 3
• Neck management depends on depth of invasion (DOI):
  • DOI <5mm and cT1N0: Active surveillance of the neck is acceptable 1
  • DOI <10mm: Sentinel lymph node biopsy is a valid option 1
  • DOI ≥10mm: Elective neck dissection is recommended 1
• Radiotherapy alone is an alternative for selected patients who cannot tolerate surgery, though surgery provides superior outcomes for oral cavity cancers. 1

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

Primary surgical resection followed by adjuvant therapy is the preferred treatment for T3/T4 oral cavity cancers. 1

• Perform composite resection (glossectomy with marginal or segmental mandibulectomy if bone involvement) plus bilateral neck dissection for midline or advanced lesions. 4, 5
• Ipsilateral neck dissection is mandatory given 84% rate of ipsilateral metastases and 61% occult metastases in clinically N0 necks. 5
• Contralateral neck dissection is indicated for midline lesions or clinically positive contralateral nodes (47% metastasis rate). 5

Adjuvant Treatment Indications

Postoperative radiotherapy is recommended for: 1

• pT3-4 tumors
• Microscopic (R1) or macroscopic (R2) positive margins
• Perineural infiltration
• Lymphatic infiltration

• 1 invaded lymph node

• Extracapsular extension

Postoperative chemoradiotherapy is mandatory for: 1

• R1 resection (microscopically positive margins)
• Extracapsular rupture/extension

The standard chemotherapy regimen is cisplatin 100 mg/m² on days 1,22, and 43 concurrent with radiotherapy (70 Gy). 1

Unresectable or T4b Disease

Concurrent chemoradiotherapy is the standard treatment for unresectable disease or T4b tumors. 1

• Cisplatin 100 mg/m² every 21 days × 3 doses with radiotherapy 1
• Alternative for cisplatin-unfit patients: carboplatin combined with 5-FU, cetuximab with RT, or hyperfractionated/accelerated RT without chemotherapy 1

Critical Pathologic Predictors

Depth of invasion (DOI) and worst pattern of invasion (WPOI) are the strongest predictors of locoregional recurrence and mortality in early-stage disease. 6

• DOI ≥4mm increases locoregional recurrence risk (HR 1.67) and mortality (HR 2.44). 6
• WPOI showing small cell islands or satellites increases recurrence risk (HR 1.46) and mortality (HR 2.34). 6
• Tumors ≥4mm deep or with aggressive WPOI should be considered high-risk requiring multimodality treatment even if clinically early-stage. 6

Key Surgical Principles

Achieving clear surgical margins is the single most important factor affecting survival. 2, 3

• Clear margins significantly improve 5-year disease-specific survival (91% vs 66% for positive margins). 3
• Occult neck metastases are the main independent predictor of survival (5-year DSS 85.5% vs 48.5%; 5-fold increased risk of death). 3
• Postoperative RT or CRT must start within 6-7 weeks of surgery to avoid compromising outcomes. 1

Recurrent/Metastatic Disease

For PD-L1 positive (CPS ≥1) recurrent/metastatic disease, pembrolizumab plus platinum/5-FU is first-line treatment. 1

• Pembrolizumab monotherapy is an alternative for PD-L1 positive tumors 1
• For PD-L1 negative disease, platinum/5-FU/cetuximab remains standard therapy. 1
• Nivolumab is approved for progression within 6 months of platinum therapy. 1

Critical Pitfalls to Avoid

• Do not use primary chemoradiotherapy for T3/T4 oral cavity cancers when surgery is feasible—surgical outcomes are superior. 1
• Do not perform inadequate neck dissection—occult metastases occur in 61% of clinically N0 necks. 5
• Do not delay adjuvant therapy beyond 6-7 weeks post-surgery. 1
• Do not ignore DOI <4mm as "low risk"—this threshold significantly impacts outcomes and should trigger consideration of elective neck treatment. 6
• Avoid single-modality treatment for high-risk pathologic features (DOI ≥4mm, aggressive WPOI, positive margins, extracapsular extension). 6, 3

Follow-Up Protocol

Clinical examination with flexible endoscopy every 2-3 months for 2 years, then every 6 months for years 3-5, then annually. 1

• FDG-PET/CT at 3 months post-chemoradiotherapy for node-positive disease to assess need for neck dissection. 1
• 89% of recurrences occur within 60 months, with 21% developing second primary cancers (54% mortality from second primaries). 2