Clinical Management of Locally Advanced Basal-Cell Carcinomas and Future Therapeutic Directions

Treatment of choice for nodular basal-cell carcinomas (BCCs) is complete excision, implying that small lesions are of minor concern. Metastasis is very rare (< 1%). However, locally advanced basal-cell carcinomas (laBCCs), which are ineligible for surgery or radiation, are a therapeutic challenge. First-generation Smoothened (SMO) inhibitors (vismodegib, sonidegib) have been approved for treatment, but common side effects limit their use. Numerous new compounds are being investigated in clinical trials as potential therapeutic alternatives, among them second-generation SMO inhibitors, other Hedgehog signaling pathway inhibitors, immune-checkpoint inhibitors and intralesional modalities such as oncolytic viruses. Neoadjuvant treatment regimens open another field. This article deals with the clinical management of laBCCs, based on the description of an illustrative case from our department featuring multiple extensive lesions of the scalp. In this short review we will discuss therapeutic options and implications for the future. Some of the new strategies might potentially evolve as alternatives in the management of genodermatoses such as basal-cell carcinoma syndrome, if proven effective and safe.