Videos

Drs Babakoohi and Atlas share clinical pearls for community oncologists on treating basal cell carcinoma.

Basal Cell Carcinoma Clinical Pearls

A look at how common metastatic basal cell carcinoma is in clinical practice and when to consider frontline immunotherapy.

Metastasis Patterns of Basal Cell Carcinoma

Experts review the safety and toxicity data of anti-PD-1 antibody agent cemiplimab for basal cell carcinoma treatment.

Safety of Cemiplimab for Basal Cell Carcinoma

Jennifer Atlas, MD, presents the case of a 66-year-old woman with locally advanced basal cell carcinoma not responding to frontline treatment.

Clinical Scenario 2: A 66-Year-Old Woman with Locally Advanced Basal Cell Carcinoma

Tell me about monitoring or follow-up visits and strategies within your clinic, Dr Babakoohi?

: For these patients, we have very close monitoring. We usually do not necessarily follow the standard rule that when you have a normal skin cancer, for example, have a skin check every 6 months. This is not the case in these situations. We see these patients much more frequently. I see them at least a couple of months after starting inhibitor therapy. Sometimes we see that they're clinically not responding. In that case, we don't need even to do a biopsy. We see that for example, large ulcerating lesion staying same, but in some cases that we see a great response, or we see a clinical feature that can be consistent with response. I proceed with scalping biopsies depending on the size of the lesion. Many times, frequently I get like 5 biopsies at the center and then 12, 3, 6, 9 o'clock to evaluate all the margins on the center for the response to see if there is any tumor present or not. The patient continues inhibitor therapy or prefers to have some type of no treatment because of adverse effects or for any other reason. We keep close monitoring. We do imaging, we take pictures frequently. I know you also do that. Make my life easier when I see your patients. This is important because we need to see the trend of changes and different pictures to not to put the patient through numerous biopsies, if we don't need that. And photo documentation, which fortunately we have the technology these days is one of the, in my opinion, necessary tools in monitoring these patients.

What would you say as far as would you expect to see a recurrence job? It's really variable and since kind of using an upfront neoadjuvant systemic approach here those objective response rates, we do see excellent responses. But that's including both stable disease, partial responses and complete responses. It’s hard to give definitive hard numbers there because there's not any neoadjuvant trial.

: I agree. I remember that when hedgehog inhibitor therapy came, there was one case series in Israel, 9 patients just off top of my head, then couple of more case 3 reports and case series came and obviously basal cell carcinoma frequently, because this is not very aggressive, especially if get hit by some treatment frequently maybe this patient don't show up for follow up. Many times, they go with other providers if they move to another city, because this is sometimes a chronic disease. It's not like some other cancers that takes people's life in matter of weeks or month. We don't know exactly how much the rate recurrence is because it's a relatively new treatment option that we have. We have that the standard numbers based on literature for a decade that for example, most micrographic surgery, 98 to 99% chance of cure or excision 95% these are traditional numbers or radiation oncology people have some numbers off top of my head. I'm not radiation oncologist at 90% depending on the location and the type of tumor. But I agree with you that we do not have solid data, obviously with a large tumor in a high-risk area. We always expect some recurrence, but I don't think there is any solid data.

What I can say is that the prognosis for locally advanced basal cell carcinoma is that amongst those 40 to 44% patients for locally advanced disease are going to have a response to a hedgehog inhibitor. The responses can be durable, and we do have a percentage of those that will have complete responses and not go on to need any additional local regional management. In my clinical practice most of these patients who have a locally advanced tumor, what my goal is from a medical oncology standpoint is in an ideal world to have a complete response, if not to try to get a partial response and work with my multidisciplinary team to go for curative therapy that may include surgery, radiation, most surgery in some format.

Shahab Babakoohi, MD, describes his monitoring strategies for patients with basal cell carcinoma.

Monitoring Strategies for Basal Cell Carcinoma

Let’s talk about systemic therapy options for locally advanced high-risk disease. I want to start first by talking about the mechanism of action of our 2 different drug classes that we can use. First-line therapy for patients who have locally advanced un-resectable disease or are not amenable to radiation would include using hedgehog inhibitors. We have 2 approved agents on the market, and they work in a similar manner. The hedgehog signaling pathway is crucial in causing basal cell proliferation and can lead to tumor growth.

Mutations can happen in one of 2 locations in this signaling pathway at patched one homolog or at SMO location, which is smoothened muscle. These are the 2 locations that we are trying to use hedgehog inhibitors for patients, which most of them are going to have mutations in those locations that lead to the pathogenesis of a basal cell carcinoma. The 2 trials that led to the approvals of these agents first with this vismodegib was the ERIVANCE trial. And secondly, the BOLT trial for sonidegib. These are our 2 commercially available hedgehog inhibitors.

The objective response rates for our 2 hedgehog inhibitors specifically with vismodegib as per data from the ERIVANCE trial is 43%. And for locally advanced patients for sonidegib is 44%. Both of these are acceptable options to administer for patients with locally advanced basal cell carcinomas. Patients will receive these medications orally and they are at flat based dosing of the medications. Looking at our other potential drug class that can be used is a PD1 inhibitor called penpulimab. This is a mechanism of action that many of us in the oncology world are well familiar with now using an anti-PD1 antibody, which is a monoclonal antibody to help recuperate the anti-tumor response of exhausted T-cells with finding two PD-L1 and PD-L2 for certain PD1 inhibitors on the tumor cell. In the study that led to the approval of cemiplimab we had patients including in cohorts that had a locally advanced cohort and a metastatic cohort. This was the 1620 study, which is a phase 2 open-label non-randomized study. On that study 84 patients had locally advanced disease. To meet eligibility criteria to go on to receive cemiplimab patients had to either have had progressive disease while on a hedgehog inhibitor were not an appropriate patient for hedgehog inhibition or patients had stable disease as their best response after nine months of therapy. Another qualifying factor was a patient who had received hedgehog inhibition but had to discontinue due to intolerance to therapy. Which initial treatment would we select for this patient, Dr Babakoohi?

: For advanced basal cell the decision is made that patient is not a candidate for surgery or radiation at the first stage, usually we proceed with inhibitor therapy trial. In some patients, if the patient responds well then in dermatology close monitoring that we do for our advanced BCC [basal cell carcinoma] patients here we monitor clinically and after couple of months on average, the time that we expect some response it can change based on our clinical exam clinical evaluation. We do surveillance biopsies from several spots of the tumor if the patient is responding which is obviously great, then the next step will be the decision or for example, if the tumor is small enough to go for surgery or depending on patients’ preference or demographic, they may want to continue patient individual therapy. In that case also we need to consider the tolerance, sometimes patients have side effects and they're tolerating because of the response, and they achieve good response. They prefer to have your input for having some intermittent therapy lowering the dose or some strategies or drug to see if they stay in remission for that. However, if our clinical evaluation shows that the patient is not responding in that case we need to go back in multidisciplinary approach and see whether patient is a candidate or surgery or radiation treatment that was not chosen at the first step because of all considerations that we discussed or if not then we need to consider second line of systemic therapy by medical oncology, which will be immunotherapy.

I agree. This patient would be an ideal patient to start with a neoadjuvant systemic approach as his frontline treatment. And that would be with a hedgehog inhibitor in this situation. And once again, with close surveillance and repeat evaluation with multiple team members, including dermatology based on response intolerance to drug, for some of those scenarios, we discussed developing intolerance or stable disease after 9 months of therapy. That may be the patient that if they are not a candidate for local regional management with either surgery or radiation with curative intent, that we would be looking at second-line systemic therapy in the form of cemiplimab, which does have based on that phase 2 study objective response rates of 29% with the vast majority of patients who fell into the response group, having partial responses, 23% were partial responses versus 6% with complete responses. It does require multiple checkpoints with the multidisciplinary team as a patient's case or care advances.

Dr Jennifer Atlas leads a conversation on systemic therapy options in basal cell carcinoma with a review of clinical trial data.

Systemic Therapy Options for Basal Cell Carcinoma

Let's review treatment options for patients with locally advanced basal cell carcinoma such as we've described in this clinical scenario. Dr Babakoohi, what do you see as the role of radiation therapy in basal cell carcinoma?

: Radiation therapy is very effective way to treat basal cell carcinoma. Response rate is great, but less than standard surgical excision when you do radiation because you have not removed the tumor so when you do follow up, you need close attention to the area for discovery recurrence at the site of radiation because radiation can cause some skin changes like that fibrotic tissue and scar like tissue that happens in the area. You need very close dermatology follow-up for very close monitoring to make sure the tumor is not back. Radiation also, it's not feasible in all the patients. For example, patients who received radiation before in that area, many times our radiation oncology colleagues are not able to provide further radiation in the same area. Also, there are some tissue scars from previous surgeries and radiation oncology colleagues sometimes hesitate to radiate the area which is already traumatized. For this purpose, also in my experience for younger patients with history of multiple skin cancers, that can be another challenge because you foresee multiple other cancers coming up and radiation several times on usual sensitive areas like face is not easily feasible. Obviously, this is something in the area of radiation oncologist specialty so they may be able to give more insight than me, but this is the experience that we see in daily practice or meetings in our multidisciplinary team meetings. Also, radiation itself after several years can increase skin cancer in radiation. For example, people who get radiation for breast cancer after 20 years there is a chance of developing skin cancers at the area of radiation. If you have a patient who is very young and you give too much radiation, you should consider that in several years, some skin cancers also can happen in that area. Overall, radiation has been beneficial in many patients, mostly in patients who are at higher risk on more your side regarding their age. And I have seen good results with radiation.

: Can you tell me about the goals of surgery for basal cell carcinoma and who's considered a surgical candidate?

: Surgery is a standard of care for skin cancer and the goal having free margins. If they removed the tumor and stop pathology shows free margins you pretty much, most likely cured the cancer, although the risk of recurrence exists in any surgery and depending on the location. In some locations, like for example, on your shoulder or your back, because the surgeon has the luxury of having enough tissue. The chance of recurrence is less because they can have very safe margin. But when they do, for example, surgery, more sensitive area, like in most micrographic surgery, close to the eyelid then it's very hard to get very large safe margin, but overall, the goal of surgery, having free margins and having no tumor more left, which is the goal.

Are there any limitations to different surgical approaches in treating basal cell carcinomas, especially the low risk versus high-risk disease?

: Yes. Standard excision that is considered you summarize where nicely the lowest basal carcinomas surgical excision, which is standard excision, just have a safe margin and take the lesion off, stitch it off or send it to pathology. That's a standard of care and can be successful in low-risk areas. It high rate of success, but for sensitive areas, like as you mentioned, face, genitalia in patients for high risk or immunocompromised the chance of having the perennial invasion or more infiltrated extension of the tumor is higher. And in these people, most micrographic surgery usually is the treatment of choice because during the procedure you look under microscope to make sure your margins are free and if not, you go back to their room and take more tissue. These 2 techniques should be used appropriately depending on the histopathology patient demographic and clinical features.

And certainly, for patients who do not meet candidacy for either curative surgical resection or radiation, then we fall back onto our systemic therapy options, which come in the form of hedgehog inhibitors and now anti PD1 antibody dosing with some cemiplimab. Those exist for patients who once again have locally advanced disease, including those with regional involvement of lymph nodes, or are metastatic patients, which is a small fraction of what we see. I see more locally advanced patients, but who may have surgeries or radiation that is being looked at in sensitive areas like we've mentioned previously, or there's a high risk that there's going to be positive margins or morbidity involved with those local regional treatments. Systemic therapy may be optimal first choice for them.

Experts review the currently available treatment options for locally advanced basal cell carcinoma.

Treatment Options for Locally Advanced Basal Cell Carcinoma

Which patients? We addressed this, but Dr Babakoohi, which patients do you see that you ultimately refer to medical oncology and at what point in their journey do you have that referral made?

: It depends on the clinical features at presentation. There are some patients that need to be referred from get-go. For example, if you see a patient who presents with a large tumor on face, not treated for many years, keep growing, approaching close to the eye or other vital organs, in these patients from the first moment that dermatologist sees the patient realizes that this is not a typical scenario to do, for example, a surgery because of functional impairment or just figuring effects or surgery, or many times they send them to surgery as the standards of care. Then surgeon evaluates the patient, realizes that the surgery will need, for example, very large complex repair causing very adverse cosmetic or functional outcomes. In those cases, from the beginning, hopefully, they are sent to medical oncology for evaluation to see if there are other approaches in multidisciplinary team approach for treatment like consideration of radiation or systemic therapy. There are some patients that, as you mentioned, in the middle of the journey are transferred to medical oncology. These are patients who initially have standard of care, for example, surgery, but during surgery or frequently most micrographic surgery because these are high-risk patients, they realize that the tumor is more aggressive or advanced than was thought initially. For example, tumor has invasion. During surgical excision, they get close to the vital organs or maybe important areas like eyes or ears, and they see that the margins cannot become clear. With these features, they need to send the patient to oncology for consideration of systemic therapy because they know that surgery is not going to clear the disease completely.

Certainly, from a medical oncology standpoint, I want to see as many patients who have high-risk features as early as possible in their journey to really weigh in not only on when the timing of systemic therapy might be of value but to help kind of in that multidisciplinary decision-making process. Do you find any challenges to bridging patients to medical oncology that you have found impact their care or outcome either from our institution or within the community?

: In our institution, obviously not. Any patients who needs medical oncology attention, we have the blessing of having you here. We don't have that barrier here. To my knowledge on the referrals that we receive, in our institution there is no barrier for receiving those patients who need medical oncology consult. The most important factor is prompt attention on time action by the primary provider who sees the patient in community. The earlier referral before proceeding with possibly multiple procedures is preferable.

From my perspective, certainly within academic institutions and as well in the community, it's all about setting the stage for a patient when they have high-risk disease. Setting that stage, it is scary sometimes to be sent to a cancer center or to be meeting medical oncology, surgical oncologist, or radiation oncologist setting that stage of we're going to have an interdisciplinary approach and team because you have high-risk disease early on, sets that stage for entry, for us to all have those various conversations. I find that once again, working in that multidisciplinary approach can really tell a patient and reassure them, hey, we have aggressive disease, but we have multiple different options for treatment and we're going to investigate what's best for you.

Dr. Shahab Babakoohi explains when to refer a patient with basal cell carcinoma from a dermatology practice to a medical oncologist.

Referring Patients with Basal Cell Carcinoma to Medical Oncology

Let’s move on to some clinical scenarios. Our first clinical scenario is a 74-year-old White man of Irish descent who presents with a 4.5-cm right auricular lesion. His medical history is significant for hypertension that’s been well controlled with medication, and his biopsy demonstrates a locally advanced infiltrative basal cell carcinoma. Let’s talk about comanagement of these patients with basal cell carcinomas, such as this patient at our institution, and how we comanage this as a team.

High-risk or advanced basal cell carcinoma needs a multidisciplinary approach. In our institution, we have a tumor board for cutaneous oncology. In our team, we have dermatologists, medical oncologists, radiation oncologists, surgical oncology, and also a micrographic surgery team. We all work together for advanced patients or high-risk patients to make the best treatment plan for them. We receive many referrals from outside providers. In those cases, almost all the time we already have the pathology diagnosis made by an outside provider. In case that patient is referred to us, we start the diagnosis and management for patients already established in our system. As an oncology dermatologist, I see them. We proceed with the biopsy. We make the diagnosis. If it’s an advanced disease, we’ll inform our medical oncology colleague Dr Atlas. From there, we’ll start working together. A patient is usually discussed in our multidisciplinary tumor board for choosing the best option for management.

You described it wonderfully. These high-risk basal cell carcinomas truly need a multidisciplinary team and approach. Each patient is going to have their care personalized to not only location but pathologic features of their disease in the context of their age and comorbidities. They’re going to need long-term surveillance and follow-up often with multiple members of the team to ensure the best care is delivered. That’s something we emphasize at our program because we not only want to treat the lesion we’re treating right now, but we also want to help prevent and do excellent surveillance additional lesions that may come, as well as manage toxicity for those who ultimately go on to receive radiation or systemic therapy. Having an interconnected group that can collaborate regularly on challenging cases is crucial to the care of these patients. In this patient, he has a locally advanced cancer that’s in a tough location in the auricular region, and it also has an infiltrator pattern. This is someone we would absolutely want to be treated in a multidisciplinary format because he has multiple high-risk features.

Jennifer Atlas, MD, presents the clinical scenario of a man with locally advanced basal cell carcinoma.

Clinical Scenario 1: A 74-Year-Old Man with Locally Advanced Infiltrative Basal Cell Carcinoma

 program titled “Basal Cell Carcinoma Treatment Advances.” I’m Dr Jennifer Atlas. I’m a medical oncologist practicing at Atrium Health Levine Cancer Institute [in Charlotte, North Carolina]. Joining me is my colleague Dr Shahab Babakoohi, who is an oncologist and dermatologist here at Levine Cancer Institute. Welcome, and thank you for joining me.

We’re going to discuss advances in the treatment of patients with basal cell carcinoma. We’ll present clinical scenarios and discuss our treatment approaches to illustrate how we incorporate data into practice to manage patients with basal cell carcinoma at our institution. Let’s get started on our first topic.

Dr Babakoohi, could you please describe the incidence patterns and patient characteristics of basal cell carcinoma?

Thanks for having me. Basal cell carcinoma is the most common skin cancer in United States, with nearly 3 million cases reported every year. The common risk factors for skin cancer are older age and history of sun exposure. These are the main risk factors we see in basal cell carcinoma. For the histopathology, there are different subtypes of basal cell carcinoma. Superficial and nodular subtypes are very common, and they are fortunately minimally aggressive compared with the others. Infiltrative morphea form or basal squamous subtypes are at higher risk of recurrence. Local invasion needs more attention.

From a medical oncology standpoint, I’m predominantly seeing the higher-risk forms of basal cell carcinoma, which is the infiltrative pattern in basal squamous carcinomas. It’s interesting because nonmelanoma skin cancers make up 80% of what we see, but only a small fraction reach a medical oncologist or a multidisciplinary team. Tell me about the testing and diagnosis that goes into treating basal cell carcinoma.

The diagnosis, almost all the time, is made by skin biopsy. Fortunately, skin biopsy is an easy procedure because skin is easily accessible, and it’s done on an outpatient basis. It takes a few minutes to do a skin biopsy. The risks are very minimal. Most of the time, histopathology is typical under a microscope. Other neuropathologist colleagues make the diagnosis very straightforward. Occasionally there’s some overlap with features of other tumors or invasive squamous subtypes. Sometimes they do special staining. But most of the time, pathology is the way to go. In cases when we have advanced basal cell carcinoma after a pathology diagnosis, patient is referred to a multidisciplinary group, including medical oncologists. Sometimes they need to do further tests, including imaging or other further evaluations, to see the extent of the disease. This happens when they come to you.

Let’s talk about how we risk stratify and categorize low-risk vs high-risk basal cell carcinomas. I wanted to start by talking about the NCCN [National Comprehensive Cancer Network] Guidelines, as well as our institution’s take on how we risk stratify these patients. When we think of low-risk basal cell carcinoma, we’re thinking of primary lesions. Typically, when we’re looking at locations, we’re talking about lesions that are under 2 cm when they’re present on the trunk or extremities and lesions on the face and other high-risk areas like the tibial that are less than 1 cm in size. We’re looking at lesions that are well defined. There’s typically no carry neural or vascular invasion. These aren’t immunosuppressed patients.

Conversely, looking at high-risk patients, we’re talking about patients with ill-defined borders. They are locally advanced tumors greater than 2 cm on the trunk and in extremity and in high-risk areas on the face, genital area, and pretibial, especially if they’re greater than 1 cm in those locations. These may be in patients who are immunosuppressed. For instance, we think about our solid organ transplant patients and our patients who maybe have autoimmune disease or other malignancies, especially hematologic malignancies that may have suppressed their immune system. We’re also thinking about patients who may have perineural invasion or vascular involvement as high-risk features and, as Dr Babakoohi described earlier, some high-risk pathologic features such as basal squamous cell carcinoma and infiltrative pattern of disease. Dr Babakoohi, can you think of any additional risk factors that help you stratify between low-risk and high-risk lesions?

You pretty much covered it. Pathology, infiltrative, and basal squamous and morpheaform basal cell carcinoma is also sometimes tricky because morphea form can show itself like an old scar on face and be undiagnosed for years. Eventually, a dermatologist takes a sample and realizes that this is morpheaform basal cell carcinoma. That’s very important because if that lesion is sitting there for years, the possibility of having more extensive disease is higher. These are the cases that, during most micrographic surgery, they realize that the extension of the disease is more than what they thought because of the chronicity of the disease.

I’ll also add to the high-risk category patients who are having recurrent lesions or lesions in sites where they have previously had surgery or radiation. Those can be certainly more challenging in high-risk cases.

Shahab Babakoohi, MD, describes the incidence patterns, options for testing and diagnosis, and risk stratification for basal cell carcinoma.

Shahab Babakoohi, MD

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