Evolving paradigms in the management of basal cell carcinoma

Basal cell carcinoma (BCC) remains the most common malignancy worldwide. While the majority of tumors are curable with surgery, a subset of locally advanced or metastatic cases requires systemic therapy. Over the last few years, a surge of translational and clinical advances has reshaped management, from Hedgehog pathway inhibition to immune checkpoint blockade and perioperative integration. This review summarizes these developments and their implications for clinical practice.

Updated evidence confirms Hedgehog pathway inhibitors (HHIs) as the standard first-line therapy for advanced BCC, while programmed death-1 (PD-1) blockade with cemiplimab has established durable responses after HHI failure. Real-world studies suggest potential benefit of earlier immunotherapy use. Emerging topical and neoadjuvant strategies, including patidegib and combined systemic-local approaches, highlight a transition toward functional preservation. Concurrently, imaging technologies such as line-field confocal optical coherence tomography and ex vivo confocal microscopy improve preoperative assessment and response monitoring, while clinical trials explore multimodal and perioperative regimens.

The modern management of BCC is evolving toward a precision-oncology model integrating molecular targeting, immunotherapy, and advanced imaging. These developments are redefining therapeutic sequencing and the boundaries between surgery and systemic treatment.