A Practical Guide for the Follow-Up of Patients with Advanced Basal Cell Carcinoma During Treatment with Hedgehog Pathway Inhibitors

Abstract

The Hedgehog pathway inhibitors (HPIs), vismodegib and sonidegib, are increasingly employed in the treatment of patients with advanced basal cell carcinoma (BCC). The aim of this review is to create a synthesis of available information in the literature regarding the follow‐up of patients with advanced BCC treated with HPIs and to provide the treating physician with a structured practical guide to standardize clinical practice. Several challenges during treatment are addressed: to optimally evaluate tumor responses, to differentiate between resistance (HPI rechallenge not possible) and recurrence (HPI rechallenge may be possible) in case of BCC regrowth, to readily assess for toxicity and tolerability issues, to provide patients with practical ways and behaviors to effectively cope with adverse events, and to improve patient adherence and quality of life. Implications for Practice This is a practical guide for clinical practice regarding the monitoring and follow‐up of patients with advanced basal cell carcinoma (BCC) during treatment with the Hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib. This review aims to bridge the gap in knowledge of assessing tumor response for BCC with both an externally visible component and an infiltrating component measurable with imaging. Furthermore, it addresses the follow‐up for adverse events as a challenging multistep process involving practices aiming to readily assess new‐onset symptoms of HPI toxicity, perform total‐body skin examination, and improve patient adherence and quality of life.

Hedgehog Pathway Inhibitors: Clinical Implications and Resistance in the Treatment of Basal Cell Carcinoma

“…Before beginning HPI treatment, it is imperative to assess the tumor in both the external/visible aspect and imaging for the infiltrating component with follow-up every three months. It is also important to stage the tumor according to the eighth TNM classification used by the Joint Committee on Cancer and Union of the International Cancer Control (UICC) [ 4 ]. For BCC of the head and neck, physical examination and imaging are used to assess the following: T (primary tumor), N (regional lymph node), and M (distant metastasis).…”

“…For BCC of the head and neck, physical examination and imaging are used to assess the following: T (primary tumor), N (regional lymph node), and M (distant metastasis). For BCC of the perianal, vulva, or penis, physical examination should determine the T, while the N and M are determined by imaging only [ 4 ].…”

“…Stable disease is defined as no increase or decrease in the size of the tumor. A progressive response, which is progression of the lesion, is a ≥20% increase in the sum of the diameters and increase in the diameter by 5 mm or the appearance of a new lesion [ 4 ].…”

“…In a study by Danial et al, primary resistance, in which the tumor never responded to treatment, occurred in 50% of the patients and secondary resistance, in which there was recurrence after the initial response to treatment, occurred in 20% of the patients [ 7 ]. Each category of resistance requires clinical examination and imaging studies for detection [ 7 , 4 ]. The cause of resistance was principally due to the mutation(s) of the SMO [ 7 ].…”

“…It is interesting to mention that recurrence after HPI discontinuation might not be due to resistance but may be explained by the persistence of a slow-cycling tumor cell population that is activating the WNT signaling pathway. The re-introduction of the HPI can achieve the same previous clinical response [ 4 ].…”