Patients with high-risk cutaneous squamous cell carcinoma are those at higher risk (>5%) of developing metastases. The majority of lesions occur on the head and neck, therefore, different specialists (dermatologists, plastic surgeons, maxillofacial surgeons, otolaryngologists) in addition to radiation oncologists may be involved in the management of these patients.
Parameters of primary, non-recurrent tumors that have been independently associated with the risk of metastasis include tumor thickness greater than 6 mm, lesions located on the ear, horizontal size greater than 2 cm and immunosuppression. The most relevant histological feature associated with increased risk of local recurrence, in addition to tumor thickness, is the presence of desmoplasia. Other factors associated with poor prognosis include recurrent lesions, incompletely excised lesions and lesions with perineural invasion. The current TNM staging classification (7th edition, 2010) has incorporated some of the above mentioned high-risk features.
For the treatment of the primary lesion, achievement of clear margins is the most important goal to prevent recurrence and locoregional metastases. The best cure rates are achieved with Mohs´ micrographic surgery. Although there are no controlled studies, adjuvant radiotherapy of the primary site has not demonstrated any benefit when clear surgical margins are obtained but it may have a potential role for cases with positive surgical margins or advanced nerve involvement.
Patients with nodal disease have 5-year survival rates ranging from 25–70%, therefore, the assessment of the lymph node status remains an important issue. The percentage of patients that have occult nodal disease ranges from 4.4% to 44.4%. Elective node dissection, widely accepted by otolaryngologists and other surgical specialists for the management of high-risk head and neck non-cutaneous squamous cell carcinoma, has not been shown to provide any survival benefit when compared to observation and subsequent neck dissection in most studies. Nevertheless, the current NCCN guidelines offer neck dissection as an option for large (T3-T4) lip tumors and recommend superficial parotidectomy if there is evidence of invasion to parotid fascia. Given its lower morbidity and its proven reliability in the staging of patients with head and neck non-cutaneous squamous cell carcinoma, sentinel node biopsy may have a definitive role for staging patients with cutaneous squamous cell carcinoma. Patients with nodal disease have an improved regional control with a significant survival benefit when combined therapy (surgery plus radiotherapy) is employed. Adjuvant chemotherapy is currently not recommended.
In the case of organ transplant recipients, a dose reduction of the immunosuppressive drug or a change to mTOR inhibitors should be consider, if appropriate.
As the first site of metastases in more than 75% of patients are the lymph nodes and the majority occur within the first 2 years after the initial diagnosis, it is recommended that patients should be followed every 3–4 months with complete clinical examination and ultrasonography for 4 years. Other imaging studies (brain MRI, body CT scan) depend on the patient´s history and clinical findings. The management of patients with high-risk cutaneous squamous cell carcinoma is complex and requires a multidisciplinary approach to achieve optimal results.