Immunotherapy in non-melanoma skin cancer: updates and new perspectives.

Abstract

The term ‘non-melanoma skin cancer (NMSC)’ includes a wide range of cutaneous tumors, including cutaneous squamous cell carcinoma (CSCC) and basal cell carcinoma (BCC), which represent the largest portion of cutaneous lymphomas. CSCC and BCC are numerically the most common human cancers in Caucasians. Their incidence and prevalence have increased constantly since 1960, from 3 to 8% worldwide, despite increased awareness of the harmful effects of sunlight.1 Distinct from other cancers, the incidence and prevalence of NMSC are not documented in a standardized manner; however, in almost all countries, the evaluation is based on small subsegments or estimates. In the United States, the annual number of cases of NMSC is, approximately, more than one million.2 In Europe, there are some regional differences, due to registration modalities, genetic background, and/or variability in public awareness and prevention measures, with a trend for an increased incidence in Northern European countries.3 In Italy, the updated AIRTUM data showed that BCC represents 15% of all neoplasms, with an annual incidence of 31.9/100,000 in males and 22.8/100,000 in females. BCC represents 80% of all NMSCs, while the remaining cases are usually CSCC. CSCC is cured by surgical measures in most cases but, in 3–5% of patients, they can progress into locoregionally advanced or, even, metastatic stages. The low percentages for advanced disease translate into an incidence for males of 4.2 out of 100,000 and for females of 2.4 out of 100,000 – numbers that indicate a ‘rare tumor-like’ occurrence.1 Currently, there is no standard therapy for patients who develop locally advanced or metastatic CSCC.4,5 As per the European Association of Dermatol-Oncology guidelines, curing tumor and preserving function with addition of cosmetics are the main goals of the primary treatment.3 Surgical resection or biopsy followed by histology should always confirm the diagnosis of precancerous lesions, before using any therapeutic modality different from surgery. Radiotherapy is a fair alternative to surgery for small CSCCs in low-risk areas, for inoperable CSCC or in the adjuvant setting.3 It may be the first option when complete resection is technically difficult or refused by the patient. Of note, radiotherapy is not curative in the advanced phase of disease.6 Platinum-based chemotherapy may be used as second-line treatment of CSCC – the response to treatment usually lasts 4–6 months and the toxicity profile precludes its use in many patients because of their pre-existing comorbidities.5 Epidermal growth factor receptor (EGFR) inhibitors can be used as subsequent line treatment when chemotherapy is unfeasible or there is a progressive disease. Cetuximab is the first chimeric monoclonal antibody anti-EGFR that showed encouraging results in the treatment of CSCC in anecdotal clinical cases5,7 and achieved a median time to treatment failure of around 4 months.7 The limitations of current treatments and their failure to achieve therapeutic targets highlight an unmet medical need for advanced CSCC treatment. In this report, we provide background on NMSC and describe the updates and new perspectives that were discussed during the symposium ‘CSCC It Bridge’ held in Naples, Italy, 28–29 November 2018.