Advanced Basal Cell Carcinoma: A Narrative Review on Current Systemic Treatments and the Neoadjuvant Approach

Background/Objectives: Systemic therapy with hedgehog pathway inhibitors (HHIs) and anti-programmed cell death protein 1 (PD-1) antibodies represent the first- and second-line treatment options for advanced basal cell carcinoma (aBCC), respectively. A shift in the treatment paradigms toward the neoadjuvant approach is gaining increasing interest in aBCC management, whereby prior systemic therapy followed by surgery is likely to yield more favorable outcomes. The aim of this narrative review is to summarize the current evidence on systemic treatment options and the neoadjuvant approach for aBCC management. Methods: We performed a non-systematic review of the literature based on PubMed as search engine. Results: The pivotal phase II trials ERIVANCE and BOLT investigated the efficacy and safety profile of vismodegib and sonidegib, respectively, with reported objective response rates (ORRs) of 60.3% and 56% in laBCC patients, respectively. The pivotal phase II trial NCT03132636 investigated the efficacy and safety profile of cemiplimab in patients who progressed or were intolerant to prior HHI therapy, with an ORR of 32.1% in laBCC patients. Real-life studies confirmed the effectiveness and safety profile of HHI and anti-PD-1 immunotherapy. Several phase I/II clinical trials are currently investigating HHIs and immune-checkpoint inhibitors in the neoadjuvant setting followed by surgery for aBCC patients, with the aim of providing more favorable treatment outcomes, especially when upfront surgery would result in functional and/or aesthetic sequelae. Conclusions: Advanced BCC treatment is challenging, and the neoadjuvant approach followed by surgery is expected to reduce surgical complexity, increase tissue preservation, and improve patients' satisfaction.