What are the treatment options for squamous cell carcinoma affecting squamous mucosa?

Treatment Options for Squamous Cell Carcinoma Affecting Squamous Mucosa

The treatment of squamous cell carcinoma (SCC) affecting squamous mucosa should be based on a multidisciplinary approach with surgery or radiation therapy as primary modalities for early-stage disease, and combined modality treatment for advanced disease. 1

Diagnosis and Staging

Before initiating treatment, proper diagnosis and staging are essential:

• Clinical evaluation including complete physical examination with neck palpation and flexible head and neck fibreoptic endoscopy 1
• Pathological confirmation through biopsy is mandatory 1
• Contrast-enhanced CT scan and/or MRI to assess the primary tumor and regional lymph nodes 1
• Chest imaging (preferably CT) to assess for distant metastases 1
• FDG-PET/CT recommended for high-risk tumors or suspected recurrence 1
• HPV evaluation using p16 immunohistochemistry for oropharyngeal SCC 1
• PD-L1 expression evaluation for recurrent/metastatic disease 1

Treatment Algorithm Based on Disease Stage

1. Early Stage Disease (T1-2N0)

Primary options (similar locoregional control rates):

• Conservative surgery 1, 2

  • Transoral approaches including transoral laser microsurgery (TLM) or transoral robotic surgery (TORS)
  • Standard excision with 4-6 mm margins 1
  • Mohs micrographic surgery for high-risk anatomic locations 1

• Radiation therapy 1, 2

  • External beam radiation therapy (EBRT)
  • Brachytherapy for selected stage I oropharyngeal or oral cavity subsites

Key principle: Early disease should be treated with single-modality treatment (surgery OR radiation) whenever possible 1

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

Primary options:

• Surgery followed by adjuvant therapy 1, 2

  • Surgical resection with appropriate margins
  • Neck dissection for nodal disease
  • Adjuvant radiotherapy or chemoradiotherapy based on pathologic risk factors

• Concurrent chemoradiotherapy 1, 2

  • Platinum-based regimens remain the standard
  • Consider for organ preservation or unresectable disease

• Induction chemotherapy followed by radiation or chemoradiation 1

  • Option for larynx/hypopharynx cancer requiring total laryngectomy

3. Very Advanced Disease (T4b and/or unresectable lymph nodes)

Primary options:

• Concurrent chemoradiotherapy 1, 2
• Induction chemotherapy followed by radiation or chemoradiation for responders 1
• Palliative treatment: systemic therapy and/or palliative radiation 1

4. Recurrent or Metastatic Disease

Treatment options:

• Surgery if resectable 1, 2
• Radiation therapy if not previously given 1
• Systemic therapy 1, 3, 4:
  • Platinum-based chemotherapy (cisplatin/5-fluorouracil)
  • EGFR inhibitors (cetuximab) 3
  • Immune checkpoint inhibitors (pembrolizumab) for PD-L1 positive tumors 4

Special Considerations for Specific Anatomic Sites

Oral Cavity SCC

• Surgery is preferred for most oral cavity SCCs 1, 2
• Depth of invasion (DOI) is an important prognostic factor 1
• If DOI <5 mm and cT1N0, active surveillance of the neck is a valid option 1
• If DOI <10 mm, sentinel lymph node biopsy is a valid option 1

Oropharyngeal SCC

• HPV status is critical for prognosis and treatment planning 1
• p16-positive tumors have better prognosis and may be candidates for treatment de-escalation 1
• Treatment options include transoral surgery or radiation-based approaches 1, 2

Laryngeal SCC

• Early glottic cancers can be treated with laser cordectomy or radiation with excellent voice outcomes 1
• Advanced laryngeal cancer may be treated with larynx preservation protocols (chemoradiation) or total laryngectomy 1, 2

Penile Intraepithelial Neoplasia (PIN)

• Circumcision is an essential component of management for most cases 1
• Treatment options include surgical excision, Mohs micrographic surgery, or distal phalanx amputation 1
• Photodynamic therapy with MAL-PDT has shown efficacy in some cases 1

Adjuvant Therapy Indications

Adjuvant therapy should be considered for high-risk features:

• Positive margins (R1 resection) 1, 2
• Extracapsular nodal extension 1, 2
• Multiple positive lymph nodes 2
• Perineural invasion 2
• Lymphovascular invasion 1

Treatment Complications and Supportive Care

• Nutritional status assessment is crucial; enteral feeding may be necessary 1, 2
• Dental examination and rehabilitation before radiotherapy 2
• Speech and swallowing function evaluation 1
• Psychosocial support 1

Follow-up Recommendations

• Physical examination every 3-6 months for the first 2 years 2
• Imaging (CT or MRI) as clinically indicated 2
• Evaluation of thyroid function at 1,2, and 5 years if radiation was delivered to the neck 2

The treatment of squamous cell carcinoma affecting squamous mucosa requires a careful assessment of tumor and patient factors. Early-stage disease can often be treated with single-modality therapy, while advanced disease typically requires multimodality treatment. A multidisciplinary tumor board discussion is essential to determine the optimal treatment strategy for each patient.