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

Treatment of Squamous Cell Carcinoma of the Tongue

Primary surgical resection followed by risk-adapted adjuvant therapy is the preferred treatment for squamous cell carcinoma of the tongue, with surgery plus postoperative radiotherapy or chemoradiotherapy being the standard approach for T3/T4 oral cavity cancers. 1, 2

Treatment Algorithm by Disease Stage

Early Stage Disease (T1-T2, N0)

Single-modality treatment should be pursued whenever possible for early disease. 1, 2

• Surgery alone is the preferred option for small, accessible lesions with adequate margins achievable 2
• Transoral laser microsurgery or transoral robotic surgery are viable conservative surgical options for selected early-stage tumors 2
• Definitive radiotherapy (external beam or brachytherapy) is an alternative for stage I cases when surgery would compromise function 2, 3
• The choice between surgery and radiotherapy should be driven by expected functional outcomes, with both modalities offering similar locoregional control for T1-T2 lesions 1, 3

Critical caveat: Even clinically N0 necks harbor occult metastases in approximately 20% of oral tongue cancers and up to 47% in base of tongue cancers, necessitating elective neck dissection for most cases beyond very superficial T1 lesions 4, 5

Locally Advanced Disease (T3-T4 or Node-Positive)

Surgery followed by adjuvant therapy is the standard approach, with primary surgical treatment being explicitly preferred for T3/T4 oral cavity cancers. 1, 2

Surgical Management

• Primary tumor resection with adequate margins (partial glossectomy, hemiglossectomy, or subtotal glossectomy depending on extent) 4, 6, 7
• Ipsilateral neck dissection is mandatory for all clinically node-positive disease 4, 6, 5
• Bilateral neck dissection is indicated for:
  • Tumors crossing midline 5
  • Base of tongue primary tumors (23% contralateral occult metastases) 5
  • Clinically positive contralateral nodes 4
  • Apex of tongue lesions 5

Indications for Adjuvant Radiotherapy

Postoperative radiotherapy is recommended for: 1, 2

• pT3-T4 tumors
• Positive resection margins (R1 or R2)
• Perineural infiltration
• Lymphovascular invasion
• More than one involved lymph node
• Extracapsular extension

Standard dose: 60-70 Gy using IMRT or VMAT 1

Indications for Adjuvant Chemoradiotherapy

Postoperative chemoradiotherapy is specifically recommended for: 1, 2

• R1 resection (microscopically positive margins)
• Extracapsular extension in lymph nodes

Standard chemotherapy regimen: Cisplatin 100 mg/m² on days 1,22, and 43 concurrent with radiotherapy (70 Gy) 1, 2

Timing is critical: Adjuvant therapy must begin within 6-7 weeks of surgery 1

Alternative to Surgery: Primary Chemoradiotherapy

For unresectable tumors or when organ preservation is prioritized, concurrent chemoradiotherapy is the standard approach. 1

• Concomitant chemoradiotherapy increases locoregional control and overall survival compared to radiotherapy alone 1
• Standard regimen: Cisplatin 100 mg/m² on days 1,22, and 43 with 70 Gy radiotherapy 1
• Alternatives for cisplatin-ineligible patients: 1
  • Carboplatin plus 5-fluorouracil with radiotherapy
  • Cetuximab with radiotherapy
  • Hyperfractionated or accelerated radiotherapy without chemotherapy

Important consideration: Margin status is the most critical prognostic factor—positive margins after surgery plus radiotherapy result in only 36% local control versus 100% with negative margins 7

Recurrent or Metastatic Disease

First-Line Systemic Therapy

For PD-L1 expressing tumors (CPS ≥1): 1, 2

• Pembrolizumab plus platinum/5-FU (when rapid tumor shrinkage needed)
• Pembrolizumab monotherapy (alternative option)

For non-PD-L1 expressing tumors: 1, 2

• Platinum/5-FU/cetuximab remains standard therapy

Second-Line Therapy

For progression within 6 months of platinum therapy: 1, 2

• Nivolumab or pembrolizumab are FDA and EMA approved options

After progression on platinum and anti-PD-1 inhibitors: 1

• Cetuximab is FDA-approved (based on single-arm studies showing 5.2-6.1 months median OS) 1
• Taxanes with or without cetuximab/methotrexate are used, though without randomized trial support 1

Critical Management Principles

Mandatory Requirements

• All treatment decisions must be made in a multidisciplinary team including surgical oncology, radiation oncology, medical oncology, speech pathology, nutrition, and dental specialists 1, 2
• Patients should be treated at high-volume facilities for improved outcomes 1, 2
• All radiotherapy must use IMRT or VMAT techniques 1, 2
• DPD testing is mandatory before initiating 5-FU to prevent life-threatening toxicity 1, 2

Post-Treatment Surveillance

• Neck dissection is NOT recommended if FDG-PET is negative with normal-sized lymph nodes at 12 weeks post-chemoradiotherapy 1, 2
• FDG-PET at 10-12 weeks post-treatment is the standard for evaluating neck response 1
• Most recurrences (40-60% in locally advanced disease) occur within the first 2 years, requiring intensive surveillance 2

Common Pitfalls to Avoid

• Do not delay adjuvant therapy: Starting beyond 6-7 weeks post-surgery significantly compromises outcomes 1
• Do not omit neck dissection in clinically N0 necks: Occult metastases are present in 20-61% depending on primary site 4, 5
• Do not use HPV status to de-escalate treatment: Treatment strategy should be identical for HPV-positive and HPV-negative disease outside of clinical trials 1
• Do not perform bilateral neck dissection routinely: Reserve for specific indications (midline crossing, base of tongue, bilateral nodes) to minimize morbidity 5