ABSTRACT
INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant tumor in adult white populations. If BCCs are not treated for years, if they cause massive destruction of the surrounding tissues, if they are considered unresectable or not eligible for radiotherapy they become progressively 'locally advanced' (laBCC) or metastatic (mBCC). These tumors are defined as 'difficult-to-treat BCC.' AREAS COVERED: A comprehensive search on PubMed was conducted to identify relevant literature about the several approved and recommended treatment options for the management of difficult-to-treat BCC published from January 2012 to July 2022. Surgical options, radiotherapy, hedgehog inhibitors, immunotherapy, and combined treatments are discussed. The keywords used were basal cell carcinoma; difficult-to-treat BCC; management of difficult-to-treat BCC; surgical therapy; radiotherapy; hedgehog inhibitors; immunotherapy. EXPERT OPINION: Identifying the best approach to DTT BCCs is one of the main challenges for the dermato-oncologist. The introduction of HHI for the treatment of advanced BCCs has revolutionized the clinical management of DTT BCCs. The immune checkpoint inhibitor cemiplimab has been approved for the treatment of locally advanced or metastatic BCC refractory to HHI therapy or in patients intolerant to HHI therapy. Multidisciplinary teams (MDTs) play a key role in managing these complex patients.