ABSTRACT
Basal cell carcinoma (BCC) is the most common form of skin cancer with a low risk of metastasis. Surgical treatment with Mohs micrographic surgery is the modality with the highest cure rate as it offers complete assessment of surgical margins, with more than 95% 5-year cure rates. Radiation therapy has a comparable cure rate with surgical excision and can be used to treat BCC in poor surgical candidates or as an adjuvant therapy for certain high-risk BCCs. For non-surgical candidates, or those with advanced disease, vismodegib, a direct smoothened (SMO) inhibitor, and other hedgehog pathway inhibitors may be used. Hedgehog inhibitors have demonstrated remarkable efficacy in the treatment of metastatic or locally advanced BCC. However, the rates of drug resistance and adverse events limit their long-term clinical benefit. Once resistance to an SMO inhibitor is encountered, switching to an alternative SMO inhibitor is unlikely to be of clinical benefit. Targeting more downstream effectors in the hedgehog pathway may be more efficacious in overcoming resistance, and further studies are investigating the best therapeutic approach to the management of BCCs resistant to SMO inhibitors. The following cases demonstrate treatment approaches to the management of advanced BCC.
