<p>Locally advanced basal cell carcinoma (laBCC) presents unique challenges to dermatologists and requires a multidisciplinary approach to treatment. For patients whose tumors are not amenable to surgery, treatment options range from local radiation therapy to systemic approaches with HHIs and immunotherapy.</p>

I do not manage laBCC directly, but I do act as a steward to good care for my patients. I want to make sure that my colleagues present patients with all their treatment options. Sometimes, you encounter someone who has a lot of comorbidities and a short life expectancy, and it may not make sense to treat their laBCC, so you just do wound care.

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For younger people who have laBCC, I try to make sure that they are getting regular skin examinations after treatment. Some patients have psychosocial issues that led them to neglect their BCC for, say, 10 to 20 years. Often, these patients require a lot of touchpoints, and you need to advocate for them and ensure that they come in for their skin checks.

I see and treat several patients with laBCC every month. For all my patients with laBCC, the first thing that I recommend is for them to have a “cheerleader.” That cheerleader may be their spouse, neighbor, or child, and they are needed because, no matter what the treatment path is, it will require some encouragement and social support.

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The first treatment that we, as dermatologists, often consider for patients with laBCC is an HHI. In the dermatology office, these are quite accessible, and dermatologists should not be afraid to use them. Vismodegib and sonidegib are the US Food and Drug Administration (FDA)–approved HHIs, and they are both taken orally once daily. The biggest issues with HHIs are the side effects, but there are ways that you can help manage them, primarily through dosing holidays or alternative dosing schedules. Patients may have to take some breaks. I have established a preference for sonidegib because it has certain pharmacokinetic properties that I believe provide an advantage, and I also have seen clinically that the side-effect profile is well tolerated.

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When an HHI is ineffective or its side effects are intolerable, we must consider immunotherapy with the PD-1 inhibitor cemiplimab. I do not provide such infusions in my office, but I utilize my medical oncology colleagues. Cemiplimab is an FDA-approved treatment for laBCC, and I have seen great responses with it. However, the biggest problem is that some patients do not receive additional treatment after an HHI has failed. We need to work on encouraging these patients to continue the fight against laBCC.

In my practice, once a patient starts an HHI, we continue it for as long as they tolerate it, or we modify the dosing schedule to give the patient drug holidays to prolong the duration of disease control. In my experience, there is very little difference between the 2 HHIs. They are both given daily, and their true limiting factors are their toxicities.

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After taking an HHI for a while, patients typically come back and say something like, “Doctor, I really can’t tolerate this drug.” They may develop dysgeusia, which, in turn, may affect their caloric intake and lead to weight loss. They may experience fatigue or muscle spasms, which can be very unpredictable. They may also develop alopecia, which is sometimes permanent. This is an important quality-of-life aspect for many of our patients with laBCC, and we have to be very respectful of that. So, we have come up with innovative ways to modify HHI dosing to limit these effects as much as possible. Studies have evaluated intermittent dosing and even stopping treatment in patients who achieve a complete response and then rechallenging them with an HHI if the disease progresses.

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Now, we also have cemiplimab for laBCC, which is used for patients whose disease has progressed on an HHI, who cannot tolerate an HHI, or who are not candidates to receive an HHI for a variety of reasons. ICIs do have side effects related to their mechanism of action, but most patients tolerate them well. However, it is important to recognize that some of these side effects can be chronic and irreversible. Side effects include endocrinopathies that may require thyroid hormone replacement, and then there are very rare side effects such as cardiac issues (eg, myocarditis) and encephalitis. So, we have to be careful with how we discuss these drugs with our older patients. It is important to provide a complete picture to the patient in terms of the pros and cons for all the treatment options.