Challenges and new horizons in the management of advanced basal cell carcinoma: a UK perspective

Abstract

Basal cell carcinoma (BCC) is a common malignancy with a good prognosis in the majority of cases. However, some BCC patients develop a more advanced disease that poses significant management challenges. Such cases include locally advanced, recurrent or metastatic BCC, or tumours that occur in anatomical sites where surgical treatment would result in significant deformity. Until recently, treatment options for these patients have been limited, but increased understanding of the molecular basis of BCC has enabled potential therapies, such as hedgehog signalling pathway inhibitors, to be developed. A clear definition of advanced BCC as a distinct disease entity and formal management guidelines have not previously been published, presumably because of the rarity, heterogeneity and lack of treatment options available for the disease. Here we provide a UK perspective from a multidisciplinary group of experts involved in the treatment of complex cases of BCC, addressing the key challenges associated with the perceived definition and management of the disease. With new treatments on the horizon, we further propose a definition for advanced BCC that may be used as a guide for healthcare professionals involved in disease diagnosis and management.

Figure 1

Example cases of complex BCCs. (A–C) Advanced facial lesions, (D) large ulcerated head lesion, (E) MRI of the patient in D demonstrating skull destruction and local invasion of the cerebellum, and (F) multiple trunk lesions.

Figure 2

The hedgehog inhibitor pathway. (A) In the absence of the sonic hedgehog ligand, the patched receptor (PTCH) inhibits the activity of smoothened (Smo), allowing suppressor of fused (SUFU) to bind to and inactivate GLI transcription factors. (B) Binding of the sonic hedgehog ligand to PTCH allows activation of Smo, inhibiting the binding of SUFU to GLI. The GLI transcription factors are then able to enter the nucleus and modulate transcription of hedgehog pathway-associated genes. (C) Vismodegib and LDE225 inhibit Smo activation, preventing inhibition of SUFU binding and subsequent changes in hedgehog pathway-associated gene transcription.