Case 4: Infiltrative Basal Cell Carcinoma

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Ahmad Tarhini, MD, PhD:Our final case is a case of infiltrative basal cell carcinoma that will be presented by Dr McKean.

Meredith McKean, MD:Case 4 is an 88-year-old man who grew up in Puerto Rico and presented to the dermatologist with a nonhealing ulcer on the lateral aspect of his nose. A biopsy was performed, and it demonstrated infiltrative basal cell carcinoma. The location and size of this lesion made surgery and radiation very difficult, and there were a number of different adverse effects anticipated from both of these treatments. The patient therefore went on to refuse both treatments and was started on vismodegib, 150 mg daily.

Ahmad Tarhini, MD, PhD:Dr Emerick, we are interested in what criteria would make this patient a surgical candidate. Is this patient a candidate for an excision or Mohs surgery, in your opinion?

Kevin S. Emerick, MD:From the tumor that we can see in that picture, certainly the patient is a candidate for surgical resection. We know that basal cell carcinoma is very responsive to surgery and has a very high cure rate. Of all the things we’re going to talk about, if we want to think about cure as our primary goal, surgery perhaps has the best overall outcome. So yes, it certainly is an option for this patient. To help guide whether this is a good candidate, we would want to have some more information about this tumor and what surgery would look like. For example, is this tumor going all the way through, such that would surgery end up creating a through-and-through defect with a large opening into the nasal cavity? That’s important because that requires, then, a big surgical reconstruction—not just the excision but a reconstructive surgery that may take weeks in a staged fashion that would have a significant impact on this patient’s quality of life. Or is it a more superficial surgical excision that could be performed in a relatively straightforward fashion with limited morbidity and limited time?

Certainly on the mind of this patient, and any patient with a tumor on their nose, is appearance, and “How will that impact on my quality of life if we surgically remove this?” Although we should probably think about that for any of the treatments and what happens when a tumor melts away from radiation or some type of a systemic therapy. If we just think about that basic question of if this patient is a surgical candidate, the answer is absolutely. But just because we can operate may not mean that we should, and that’s where hidden in that nuance is talking to the patient a bit, understanding what their goals are. We have some patients who are going to prioritize cure, saying “Whatever it takes, Doc. As long as this never comes back.” This might be different for a patient based on their age. Someone who is 88 years old, like this patient, can come in a lot of different flavors that may or may not have a long life expectancy that may have an impact on how they guide us on a role of surgery or other treatments.

Ahmad Tarhini, MD, PhD:Going back to your advice about multidisciplinary discussion, to the community practitioner, how should this case be approached?

Kevin S. Emerick, MD:Recognizing that there are multidisciplinary treatment options is the first step. I would suspect this patient might start in a dermatology office, maybe even before they get to a Mohs [surgery] office. It’s important for the folks in the community to recognize there are different roles. That’s the first step, and I think that when you know there are options, it helps encourage us to make sure that those patients hear those options. If it’s in a great, well-organized multidisciplinary clinic, that’s fantastic. But if not, maybe by finding some key people in your community, you could have an efficient series of visits. Or maybe you could even have a virtual tumor board and a conversation over the phone that may help provide options to that patient and guide both the team and the patient to the best option.

Ahmad Tarhini, MD, PhD:Sounds great. Let’s talk about the role of radiation therapy. What patients do you think should go to radiation rather than surgery?

Kevin S. Emerick, MD:I think patients with basal cell carcinoma are generally very responsive to radiation, so it is worth considering. We have to think about, in terms of, if it is perhaps less effective than surgery. When we think about the adverse effects or radiation, they start to offset that appealing part where we say, “Oh, good, we could avoid surgery.” But radiation is an everyday Monday-through-Friday treatment for about 6½ weeks in order to get the effect that you want for this type of a tumor. That might be OK for some patients, but for many patients in this setting who are 88 years old, that actually becomes a much greater wear and tear in terms of fatigue daily, getting in for treatment, getting up on the treatment table, and so forth. That may actually have more morbidity than surgery or a systemic treatment. It is an option, but perhaps not our first option because of those issues we just talked about.

Ahmad Tarhini, MD, PhD:Dr McKean, in your mind, what are the goals of treatment? What are we trying to achieve with this patient?

Meredith McKean, MD:It’s interesting. This is an 88-year-old patient. Back to the point about any 88-year-old can look very different, age is a number. For this patient, if they have a number of comorbidities, this may be trying to alleviate their symptoms—the pain, the discomfort that they’re having—and considering that as your goal for these treatments versus trying to actually help this patient live longer from the long-term risk of this metastasizing elsewhere.

Ahmad Tarhini, MD, PhD:Agreed. Obviously, we would also work on maintaining function and structure if possible, without disfiguring surgery if indicated. Dr Wong, what are the options in terms of systemic therapy for this patient?

Deborah J. Wong, MD, PhD:Fortunately, for patients who either are not candidates for a local therapy or choose not to undergo local therapy, we do have 2 FDA-approved agents for basal cell carcinoma that’s locally or advanced, unresectable or even distantly metastatic. They’re hedgehog inhibitors. The first is vismodegib and the second is sonidegib. They work by inhibiting the hedgehog pathway, so they’re small-molecule inhibitors of a cell surface receptor called smoothened. This pathway is known to be hyperactive in basal cell carcinoma.

Ahmad Tarhini, MD, PhD:Going back to the case, our patient was treated for 6 months with vismodegib until there was no evidence of basal cell carcinoma. He was then sent to the dermatologist for several blind biopsies in this area. All biopsies came back negative for basal cell carcinoma, and vismodegib was discontinued. He remains disease-free at the last follow-up. One thing is tolerability and adverse effects. Dr McKean, can you comment on the expected adverse events of hedgehog inhibitors?

Meredith McKean, MD:With hedgehog inhibitors, there is a unique profile. These patients can have some of the same targeted therapy adverse effects of fatigue and nausea. Some of the other things that we see, though, are debilitating muscle spasms and other adverse effects that may require either holding therapy or having additional medications on board.

Ahmad Tarhini, MD, PhD:In terms of duration of treatment, Dr Wong, how long would you treat?

Deborah J. Wong, MD, PhD:These treatments are started with the idea to continue them until unacceptable toxicity or until disease progression. Fortunately, what we’ve seen from the data is that, in fact, we can have quite durable responses. I think with vismodegib, progression-free survival in the landmark study was 22 months, and that was both for locally advanced as well as distantly metastatic disease. We are seeing that patients can do quite well on therapies. As Dr McKean mentioned, the adverse-effect profile is unique, and it can be limiting in terms of treatment intensity. In the studies, we’ve seen almost a third of patients who have to discontinue therapy because of adverse effects—muscle spasms, dysgeusia, alopecia, and the like.

Ahmad Tarhini, MD, PhD:When we achieve the goal that we’re looking for, that’s probably a time to stop as well. In this case, it was interesting to see that the patient achieved a complete response. The biopsy came back negative for disease, and in my practice, I would do the same. I would hold the drug and monitor these patients closely. I have done, in some cases, a treatment holiday or given patients a break, treated for a few weeks, and then they took a holiday for a few weeks. Then we can treat again, dose reduce to tolerance, and so on.

Transcript edited for clarity.