The evolving guidance from professional societies reflects the growing knowledge of the pathogenesis of non-melanoma skin cancers (NMSCs) and ongoing clinical research on systemic therapy for BCC. Several guidelines worldwide, including those from the National Comprehensive Cancer Network® (NCCN), American Academy of Dermatology (AAD), and European Association of Dermato-Oncology (EADO), recommend the use of Hedgehog inhibitors (HHIs) to treat “difficult-to-treat” BCC, such as locally advanced BCC (laBCC), metastatic BCC (mBCC), and Gorlin syndrome. For patients with laBCC or mBCC that are relapsed or refractory to HHIs, or for those intolerant or unsuitable for HHIs, an approved anti-PD-1 therapy is recommended by the Society for Immunotherapy of Cancer (SITC) clinical practice guidelines.
Metastatic BCC is exceedingly rare, with an estimated incidence of 0.0028% to 0.55%, and has historically been associated with a very poor prognosis. The most common progression pathway involves lymphatic metastasis to regional lymph nodes, followed by hematogenous spread to the lungs and bones.1