What are the treatment options for squamous cell carcinoma of the skin?

Treatment Options for Cutaneous Squamous Cell Carcinoma

Surgical excision is the treatment of choice for the majority of cutaneous squamous cell carcinomas (cSCCs), with specific surgical approaches determined by risk stratification of the tumor. 1

Risk Stratification

Before selecting treatment, it's essential to categorize cSCCs as either low-risk or high-risk:

Low-Risk Features:

• Small size (<2 cm)
• Well-defined borders
• Located on trunk or extremities (non-terminal hair-bearing areas)
• Well-differentiated histology
• No perineural invasion
• Immunocompetent patient

High-Risk Features:

• Large size (≥2 cm)
• Located on high-risk areas (ear, lip, scalp, eyelids, nose)
• Poorly defined borders
• Recurrent lesions
• Moderate to poor differentiation
• Perineural invasion
• Immunosuppressed patient
• Tumor extending into subcutaneous tissue

Primary Treatment Options

For Low-Risk cSCC:

1. Standard Surgical Excision

   • Recommended with 4-6 mm margins to a depth of mid-subcutaneous adipose tissue 1
   • Histologic margin assessment required
   • Expected to completely remove the primary tumor in 95% of cases 1
   • Allows full characterization of the tumor

2. Curettage and Electrodesiccation (C&E)

   • May be considered for low-risk primary cSCC in non-terminal hair-bearing locations 1
   • Not recommended for:
     • Hair-bearing sites (risk of follicular extension)
     • When subcutaneous layer is reached during procedure
   • If performed, biopsy results should be reviewed to ensure no high-risk features are present 1

3. Radiation Therapy

   • Option when surgical therapy is not feasible or preferred 1
   • Understanding that cure rates may be lower than with surgery
   • Various forms include superficial radiation therapy, brachytherapy, external electron beam therapy 1

4. Cryosurgery

   • May be considered for low-risk cSCC when more effective therapies are contraindicated or impractical 1
   • Lower efficacy than surgical options

For High-Risk cSCC:

1. Mohs Micrographic Surgery (MMS)

   • Recommended treatment for high-risk cSCC 1
   • Provides complete peripheral and deep margin control
   • Maximizes tissue conservation while ensuring complete tumor removal
   • Particularly valuable for:
     • Recurrent tumors
     • Poorly defined tumors
     • Sclerosing/infiltrative subtypes
     • Cosmetically sensitive areas

2. Standard Excision with Wider Margins

   • 6 mm or more margin recommended for high-risk tumors 1
   • With histological examination of tissue margins
   • May be considered for select high-risk tumors, but caution advised without complete margin assessment 1

3. Excision with Complete Circumferential Peripheral and Deep Margin Assessment (CCPDMA)

   • Alternative when Mohs surgery is unavailable 1
   • Must include complete assessment of all deep and peripheral margins

Management of Advanced Disease

For Regional Lymph Node Metastases:

• Surgical resection with or without adjuvant radiation therapy and possible systemic therapy 1
• Combination chemoradiation therapy for inoperable disease

For Locally Advanced or Metastatic Disease:

• Epidermal growth factor inhibitors (cetuximab) and cisplatin may be considered 1, 2
• Multidisciplinary consultation and management, particularly in immunosuppressed individuals 1
• Palliative care to optimize symptom management and maximize quality of life

Common Pitfalls and Caveats

1. Deep Margin Involvement: Most incomplete excisions (94%) involve the deep margin rather than radial margins 3. Ensure adequate depth of excision, particularly for tumors on the ear, nose, and cheek.

2. Residual Disease: Approximately 28.6% of incompletely excised primary cSCCs show residual tumor in re-excision specimens 4. Larger tumors and those with greater Breslow thickness are more likely to have residual disease.

3. Delayed Treatment: A longer delay between initial excision and re-excision may result in less residual tumor 4, possibly due to regression of remaining tumor cells.

4. In-Transit Metastases: cSCC may give rise to local metastases discontinuous with the primary tumor. These "in-transit" metastases require wide surgical excision or irradiation of a wide field around the primary lesion 1.

5. Topical Therapies: Topical therapies (imiquimod, 5-FU) and photodynamic therapy are not recommended for invasive cSCC based on available data 1.

Follow-up Recommendations

• After diagnosis of a first SCC, screening for new keratinocyte cancers and melanoma should be performed at least annually 1
• Patients should be counseled on skin self-examination and sun protection
• More frequent follow-up for high-risk patients: every 3-6 months for 2 years, then every 6-12 months for 3 years, then annually for life 1

Remember that the goal of treatment is complete removal or destruction of the primary tumor and any metastases, with histological confirmation when possible 1.