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

Abstract

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.

Neoadjuvant Therapy for Non-melanoma Skin Cancer: Updated Therapeutic Approaches for Basal, Squamous, and Merkel Cell Carcinoma

“…By definition, a neoadjuvant approach aims to reduce the size of the tumor, in order to make it eligible for other potentially curative techniques. The most typical circumstance requiring a neoadjuvant treatment regards advanced tumors, when there may be a significant risk of functional and cosmetic deficit from immediate surgery because of size, number, or location of the cancers [ 10 , 11 ]. In evaluating tumor response to treatment, RECIST (Response Evaluation Criteria In Solid Tumors) criteria are often used, defining complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) [ 12 , 13 ].…”

Qualitative Patient Interviews to Characterize the Human Burden of Advanced Basal Cell Carcinoma Following Hedgehog Pathway Inhibitor Treatment

“…Surgical excision, when possible, is the standard treatment of BCC. However, inadequate or incomplete excision increases the risk of recurrence, and such tumors may require re-excision [ 3 – 5 ]. Fewer than 1% of cases progress to locally advanced or metastatic disease, collectively referred to as advanced BCC (aBCC) [ 6 ], and may consequently require systemic therapy [ 7 ].…”

“…European Medicines Agency (EMA) and US Food and Drug Administration (FDA)-approved and guideline-recommended therapies that target the hedgehog signaling pathway (hedgehog pathway inhibitors, HHIs) have been used as a first-line systemic therapy against aBCC not amenable to curative surgery or radiotherapy. Eventual discontinuation of first-line HHI therapy is common because of progression of disease or adverse events [ 3 – 5 , 8 – 14 ]. In 2021, the FDA and EMA approved the use of cemiplimab, a programmed cell death-1 inhibitor, for the treatment of patients with aBCC previously treated with an HHI or for whom an HHI is not appropriate [ 15 ].…”

Treatment of Nevoid Basal Cell Carcinoma Syndrome by Surgery Combined With ALA-PDT: A Case Report

“…Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin-Goltz syndrome, is a rare multisystem disease caused by a mutation in the patched gene. 1 It is inherited in a dominant autosomal manner with complete penetrance and variable expressivity. This syndrome is characterized by multisystem abnormalities, especially the early appearance of multiple basal cell carcinomas.…”

“…Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin–Goltz syndrome, is a rare multisystem disease caused by a mutation in the patched gene 1 . It is inherited in a dominant autosomal manner with complete penetrance and variable expressivity.…”