Keratinocyte skin cancer, consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is by far the most common cancer in white-skinned populations, with rapid increases over the last 50 years. While the age-standardized incidence rates increase worldwide, the age-standardized mortality rates are variable. The incidence rates of keratinocyte skin cancer are much higher compared to those of melanoma, and are largely attributed to the raising exposure to ultraviolet (UV) radiation, the most important causal risk factor for skin cancer. Whereas the development of BCC is mainly due to intense UV exposure during childhood and adolescence, the development of SCC is related to chronic, cumulative UV exposure over decades. Although mortality rates are relatively low, SCC is an increasing problem for healthcare services, significantly causing morbidity, especially in older age groups. This review reports on the epidemiology of keratinocyte skin cancer, with a focus on SCC, in Australia, the United States, and the north of Europe, with an outlook on further challenges health systems will be confronted with in the next 20 years.

For rare skin cancers, few data exist on the outcome of systemic therapies, particularly immune checkpoint inhibition (ICI). The present study analysed the real-world use of different systemic therapies including ICI, and its outcome in patients with advanced rare skin cancers. This retrospective multicenter study included patients who received systemic therapy for advanced, non-resectable cutaneous angiosarcoma (AS), Kaposi sarcoma (KS), pleomorphic dermal sarcoma (PDS), or cutaneous adnexal carcinoma (CAC). Study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS). 209 patients (77 AS; 81 KS; 14 PDS; and 37 CAC) from 30 centers were included. As first-line treatment AS and KS patients predominantly received chemotherapy (77.9 %; 63.0 %), while PDS and CAC patients mostly received ICI (64.4 %; 43.2 %). BOR in first-line across all therapy types was 65.5 % in KS, 50.0 % in PDS, 41.6 % in AS, and 10.8 % in CAC. BOR for ICI was 66.6 % for PDS, 58.3 % for AS, 33.3 % for KS, and 4.3 % for CAC, irrespective of treatment line. 1-year PFS rate upon any first-line therapy was 70.7 % for PDS, 45.7 % for KS, 25.6 % for AS, and 18.5 % for CAC (p < 0.001). 1-year tumor-specific OS rate was 97.3 % in KS, 84.2 % in AS, 67.7 % in PDS, and 65.4 % in CAC (p < 0.001). Type and outcome of systemic therapy differed between cancer entities. Efficacy of ICI was high in PDS and AS, moderate in KS, and low in CAC. Patients with advanced CAC revealed an extremely poor prognosis regardless of the type of therapy used.