Cutaneous Squamous Cell Carcinoma

Background

• Squamous cell carcinoma (SCC) of the skin is the second most common malignant, keratinocyte skin cancer.
• Risk factors for cutaneous SCC include age > 50 years, fair skin or hair, chronic exposure to ultraviolet (UV) light, immunosuppression, exposure to photosensitizing medications, chronic trauma or burn injury, and a family or personal history of nonmelanoma skin cancer.
• The prognosis is generally excellent for patients with low-risk disease, with a 5-year survival of 98%.
• About 40% of patients with keratinocyte skin cancer will have another keratinocyte skin cancer within 5 years.

Evaluation

• Patients usually report a history of a nonhealing skin lesion on a sun-exposed area that appears indurated, scaly, or hyperkeratotic. Cutaneous squamous skin carcinoma may be preceded by actinic keratoses.
• Examine the lesion and consider a complete skin exam to look for other undetected lesions.
• Differential diagnosis includes other skin cancers, verruca (wart) actinic keratosis.
• Histopathology of a biopsy or excised lesion is required for a diagnostic confirmation.
• Obtain imaging for high-stage tumors or if extension or lymph node involvement is suspected.
• Tumor-node-metastasis (TNM) staging of cutaneous SCC is based primarily on the size, depth, and presence of local or distant metastasis.
• Tumors may be staged by one of several systems, such as the American Joint Committee on Cancer system, the Brigham and Women's Hospital staging systems, or other alternatives.

Management

• The approach to treatment of cutaneous SCC is based on whether risk factors for recurrence or metastases are present.
  • Clinical factors associated with a low risk for recurrence or metastases include small size (≤ 2 cm) and presence on the trunk or extremities (but NOT on the hands, feet, or pretibial regions), slow-growth, well-defined borders, absence of prior SCC or prior radiation therapy or chronic inflammation at the same site, and no history of immunosuppression or organ transplant. Favorable pathologic features include < 6-mm depth and well-differentiated histology.
  • SCC associated with high risk of recurrence or metastases include any tumor located on the head, neck, hands, feet, pretibial or anogenital region, as well as any larger truncal/extremity tumors (> 2 cm).
  • Factors associated with very high risk of recurrence or metastases include tumor size > 4 cm, > 6-mm depth, or invasion beyond subcutaneous fat, or lymphatic, vascular, or perineural invasion. Additional high-risk factors include recurrent lesions or lesions with rapid growth, poorly defined borders, at sites of radiation therapy or chronic inflammation, or in patients with history of immunosuppression or organ transplant.
• For management of local cutaneous squamous cell carcinoma:
  • Use surgical excision as the primary treatment (Strong recommendation). Options are standard surgical excision with 4- to 6-mm margins or Mohs micrographic surgery, unless the patient is not a surgical candidate.
  • Mohs micrographic surgery is preferred for lesions on the head, neck, hands, feet, pretibial, or anogenital area, and for high-risk lesions and lesions at other sites where wide margins are difficult to achieve without cosmetic or functional impairment.
  • If standard surgical excision is being utilized, clear margins should be obtained before permanent closure if tissue rearrangement or skin grafting is needed.
  • Consider electrodesiccation and curettage as an option for low-risk, well-defined lesions that are NOT on the scalp, or in pubic, axillary, or beard regions (Weak recommendation). The lesions should be biopsied in entirety, and pathology should be reviewed to avoid missing aggressive, high-stage tumor.
  • Offer primary radiation therapy or less invasive treatments such as electrodessication and curettage, cryotherapy, or topical chemotherapy for patients who are unable or unwilling to undergo surgery, keeping in mind that these treatments are associated with a higher risk of tumor recurrence .
  • Periodic in-office follow-up every 3-6 months is suggested to monitor for recurrence or second primary SCC.
• Lymph node evaluation
  • If lymph node involvement is suspected by physical exam or imaging, obtain fine needle aspiration (FNA) or core biopsy under ultrasound guidance (Strong recommendation).
  • For high-risk or recurrent cutaneous SCC, consider a sentinel lymph node biopsy (Weak recommendation).
• For locally advanced, recurrent or metastatic SCC
  • Consider multidisciplinary team consult for patients with locally advanced, recurrent or metastatic SCC (Weak recommendation).
  • Offer adjuvant radiation therapy for SCC with positive tissue margins after excision or SCC with marked perineural involvement or recurrent invasion (Strong recommendation).
  • For locally advanced SCC that is not curable by surgery or radiation, consider immunotherapy with an immune checkpoint inhibitor, such as pembrolizumab or cemiplimab-rwlc (Weak recommendation).
• For patients with positive lymph nodes
  • Consider regional lymph node dissection and adjuvant radiation therapy if multiple nodes are involved and/or there is extracapsular involvement of lymph nodes. Patients with a single small (≤ 3 cm) involved node without extracapsular extension are at low risk for regional failure and death and can be treated with regional lymph node dissection alone (Weak recommendation).
  • For lymph nodes with extracapsular extension or incompletely excised nodal disease, consider lymphadenectomy plus radiation therapy (Weak recommendation).
• For nodal or distant metastases, consider multidisciplinary team consult and systemic therapy with options of:
  • immunotherapy with an immune checkpoint inhibitor, such as pembrolizumab or cemiplimab-rwlc (Weak recommendation)
  • targeted therapy with epidermal growth factor receptor (EGFR) inhibitor, such as cetuximab (Weak recommendation)
  • traditional chemotherapy (Weak recommendation)
  • clinical trial (preferred) (Weak recommendation)

Prevention and Screening

• For the prevention of skin cancer:
  • Consider counseling patients aged 10-24 years who have fair skin about minimizing exposure to UV radiation to reduce the risk of skin cancer (Weak recommendation).
  • Consider counseling patients > 24 years old with fair skin plus ≥ 1 risk factor for skin cancer on minimizing UV radiation exposure. Risk factors for skin cancer include (Weak recommendation):
    • history of sunburns or use of indoor tanning beds
    • personal or family history of skin cancer
    • higher number of nevi and atypical nevi
    • compromised immune system (such as in patients with HIV infection or those who have received an organ transplant)
  • Daily sunscreen application may help reduce the incidence of cutaneous squamous cell carcinoma.
• Consider treatment of actinic keratoses and squamous cell carcinoma in situ to prevent the development of invasive SCC (Weak recommendation).