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Advanced Non-Melanoma Skin Cancer Treatment | Partnering With Your Team on Care Decisions

Advanced Non-Melanoma Skin Cancer Treatment | Partnering With Your Team on Care Decisions from Patient Empowerment Network on Vimeo.

 When making advanced non-melanoma skin cancer care and treatment decisions, what factors help determine the best approach for YOUR disease? Dr. Soo Park reviews current treatment options, emerging research, and shares advice for partnering with your healthcare team.

Dr. Soo Park is a Medical Oncologist at Moores Cancer Center at UC San Diego Health. Learn more about this expert.

 

Related Resources:

An Expert’s Perspective on Advanced Non-Melanoma Skin Cancer ResearchAn Expert’s Perspective on Advanced Non-Melanoma Skin Cancer Research What Do You Need to Know About Advanced Non-Melanoma Skin CancerWhat Do You Need to Know About Advanced Non-Melanoma Skin Cancer? What Is Non-Melanoma Skin Cancer?


Transcript:

Katherine:

Hello and welcome. I’m your host, Katherine Banwell. In today’s program, we’ll be discussing advanced non-melanoma skin cancer, what it is, how it’s treated, and you’ll learn tools for advocating for yourself.   

This program is part of the Patient Empowerment Network toolkit series, which was created with the goal of helping patients learn more about their cancer and empower them to play a proactive role in their care. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to program materials. If you haven’t already, click that link to access a guide to help you follow along during the webinar.  

At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today, in order to help us plan future webinars. And finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you.  

Well, let’s meet our guest. Joining us is Dr. Park. Welcome. Would you please introduce yourself?  

Dr. Park:

Great, thanks. So, my name is Sue Park, and I’m an associate professor of medicine at the University of California here in San Diego, and I focus on cutaneous oncology. So, I see patients with all types of skin cancers. And in particular, I focus on non-melanoma, because I think most patients realize that the other skin cancer that is widely known is melanoma.   

Katherine:

Okay, that’s great. Thank you so much for dividing that up, and thanks for taking the time to join us today.  

Dr. Park:

Yeah, of course.  

Katherine:

So, Dr. Park, non-melanoma skin cancer is a group of cancers. Would you define it for us?  

Dr. Park:

Yeah, so, non-melanoma skin cancers is just basically a broad blanket term for any skin cancer that is not a melanoma. And so, that’s things like basal cell skin cancer, squamous cell skin cancer, Merkel cell skin cancer. So, anything that’s not considered a melanoma. A melanoma is another type of skin cancer, but it develops from a different type of skin cell.  

Katherine:

Okay, that’s good to know. So, what are the most common types of non-melanoma skin cancer? I think you’ve just mentioned that, but maybe you could mention them again, and maybe define each one.  

Dr. Park:

Yeah, so, there are lots of different types of non-melanoma skin cancers, but the two most prevalent ones are basal cell skin cancer and squamous cell skin cancer, and they actually both come from the same cell of origin in the skin. but there are actually two different types of skin cancers because ultimately that one cell, develops into another cell.  

And so, for basal cell skin cancer, the cell that it comes from is a basal cell, and that’s why it’s called basal cell skin cancer. And that is very different than squamous cell skin cancer. So, as the name says, squamous cell skin cancer actually comes from a squamous cell, and these are both cells that are in your skin, and both of these cancers are mainly driven by the sun exposure.  

But even though they’re both non-melanoma skin cancers and they’re the most common, with basal cell being the number one most common skin cancer actually in the world, I think a lot of people don’t recognize that, because we don’t capture the occurrences of basal cell skin cancer very well, because it’s so common. But those are the two main types of skin cancers that I think a lot of treatments are focused on right now.   

Katherine:

And are these cells – can they develop into cancer anywhere on the body, on the skin of the body?  

Dr. Park:

Yeah, so, anywhere that you have any type of cutaneous skin, these cells reside, and typically they happen in areas where the skin is exposed to the sun. So, for example, they often happen on the head and neck, because we just get lots of sun exposure there.  

Katherine:

Yeah, yeah, okay. So, who typically diagnoses this stage of skin cancer? Is it a dermatologist, or somebody else?  

Dr. Park:

So, that really depends on the stage of the skin cancer. So, when I say stage, I mean how advanced is it. For an early stage skin cancer, those are typically really small. And oftentimes, patients will have a few of these; and some patients have a lot of these, maybe on their face, their neck, their scalp, across their hands and arms. And typically, they notice a small lesion that won’t go away or is getting a little bit irritated.  

And so, they see the dermatologist first. So, the dermatologist is often the first person that sees patients whenever the patient has noticed like a small skin abnormality that’s not getting better. But sometimes, they also see patients that do not see the dermatologist first.  

They actually either see a medical oncologist like myself, or a head and neck surgeon who I work closely with, because some patients have a tumor or a cancer that’s really large, and it’s too large to the point where a dermatologist is not able to offer them anything. And so, if the tumor is really large, that’s a later stage cancer. So, it’s not as stage.  

Katherine:

Yeah. Now, this may seem like a silly question, but don’t the cells sometimes show up at like a mole, so you wouldn’t even know you had it?  

Dr. Park:

Yeah. So, that’s more common for melanoma. It can show up as a mole, but you’re exactly right. For both non-melanoma skin cancers like basal cell and squamous cell skin cancer, it can look just like a little lesion that you might have thought you hit yourself on like the door handle, and it’s not getting better.  

Some of these cancers actually appear, and then they go away on their own, and then they come back. And so, sometimes it’s really hard to see that it is a skin cancer, it was a skin cancer. But I think what’s really important is that it’s a lesion that’s either getting worse, or it’s not going away, so you should really tell your doctor about.  

Katherine:

Yeah. We know that there’s a multidisciplinary team involved with advanced non-melanoma skin cancer care. Who are the members on the team?  

Dr. Park:

So, I think now, because we have so many more treatments to offer patients, if I’m specifically talking about a non-melanoma skin cancer on the head and neck, which is where it most commonly occurs, because of sun exposure, I think the multidisciplinary team is really important. That typically consists of a medical oncologist like myself, typically a head-and-neck surgeon, and sometimes a plastic surgeon, as well, depending on what we come up with as a treatment plan.  

It also often involves a radiation oncologist. So, that’s a special type of doctor that gives radiation treatment. We always want to keep the dermatologist involved, as well, because most of these patients do have a primary dermatologist that’s been really involved in their care.  

Katherine:

What about other people on the healthcare team, like that are in a supportive form on the team? 

Dr. Park:

Yeah, that’s just as important, because a lot of these patients may have barriers to care, or they may have social factors that affect their ability to get the care that they deserve, and that they need. 

So, we work really closely with social workers, with nurse navigators, even speech therapists. Sometimes if the cancer is involving some really close to your lip or mouth, sometimes that can be really difficult. We work a lot with audiologists, as well. So, we have a really great multidisciplinary team.  

Katherine:

So, once a patient has been diagnosed, what are the tests that help understand more about the patient’s individual disease?  

Dr. Park:

So, it’s always important to get a biopsy, so then we can tell which type of non-melanoma skin cancer it is. 

And that’s when we look at your cancer under the microscope, and a special doctor called a pathologist. And actually, they’re also really important as part of our multidisciplinary team. They look at the tumor under the microscope, and they help us decide and tell us which type of non-melanoma skin cancer it is. 

But aside from that, I think imaging is really important. So, that are things like CT scans, MRI scans. Sometimes we have to also recommend a PET scan, which is another type of special scan. And these images are really to help us look deeper into the structure of your body, because I can only see so much from the outside.  

And they can really help us tell how deep is the cancer; is the cancer around any critical structures? Is it anywhere else in the body? Because if we find cancer far away from where it originally occurred, that may tell us that the cancer is a later stage.  

Katherine:

So, let’s just go with a scenario. Somebody comes in to you, and they have a lesion on their cheek, for instance.   

Would you do a whole body MRI or a CT scan to see if that…once you’ve done a biopsy, you find that it’s cancerous. Would you do a whole body MRI, or a scan of some sort, to see if the cancer was anywhere else?  

Dr. Park:

So, we typically don’t, because we know the patterns that – for instance, like you mentioned, like a skin cancer in your cheek can go to. And so, non-melanoma skin cancers on the face or anywhere in the body, they typically like to go to the lymph nodes that drain that area. And so, if you have a lesion on your face, that’s typically your neck.   

And so, we’ll do a good exam of your face, your neck, but we will also get imaging of those areas. So, we typically get an imaging focused on the head and neck. If we find something abnormal there, then that may tell us we need additional imaging in the other parts of the body. But more often than not, we don’t start with a whole body scan.  

Katherine:

Okay. What questions should patients ask about their test results?  

Dr. Park:

So, I think patients should definitely ask, “What type of skin cancer do I have? How did it arise? Where all in my body is the skin cancer? What does my blood work look like?” And I think patients should also be aware that for many years now, we send tumor samples for something called molecular sequencing, and that just tells us different types of mutations that may be in your tumor. And that’s really important, because there are some drugs we have now that are only for patients that have specific mutations in their tumor.  

And so, if you are one of those patients that has a specific mutation, that opens the door to another type of therapy for you. And, you know, that’s something that’s now recommended, actually, by a lot of cancer societies, to really send your tumor for some type of molecular sequencing, so we can level the playing field for all patients, and offer them the full range of treatments that we have.  

Katherine:

Yeah. What are the common mutations?  

Dr. Park:

So, for basal cell skin cancer, almost all basal cell skin cancers are driven by abnormality in a certain pathway called the hedgehog pathway. Yeah, I’m – 

Katherine:

Interesting. Why? 

Dr. Park:

It was named, I think, by someone. All these names are people by someone that discovered it, and they get the rights to name the pathway. But for a basal cell, it’s the hedgehog pathway. And so, in the hedgehog pathway, there are certain types of mutations specifically associated with that pathway. And one of them, among these mutations, we look for drugs that can inhibit this pathway. So, there are drugs that specifically target the hedgehog pathway.  

They’re called hedgehog inhibitors, and they’re oral medications or pills that you can take every day. And those are for patients with basal cell skin cancer, because the basal cell skin cancer came about because the hedgehog pathway is not normal. But for squamous cell skin cancer, squamous cell skin cancer often has a lot of mutations. And unfortunately, they’re the type of mutations that we actually don’t have a drug for at this moment. But one unique thing about squamous cell skin cancer is that it has so many mutations.  

And so, that means that it has a better chance of responding to a different type of treatment. It’s an IV treatment known as immunotherapy. And so, that’s something that’s relatively recent, I think, in the past five years now. We’ve started using immunotherapy for patients that have squamous cells skin cancer, and it’s worked remarkably well.  

Katherine:

How do these cancers typically progress? What are the stages?  

Dr. Park:

Yeah, so, if it’s just a really small cancer like that’s on your face, it’s typically an early stage or a stage I. And I’m specifically talking about squamous cell skin cancer, because actually for basal cell, we don’t have any formal staging for basal cell.  

Katherine:

Why is that? 

Dr. Park:

It just wasn’t included in the staging systems. So, for basal cell, there’s no formal staging criteria, but we’ll stage it as early stage based on what we think, as a clinician, when we see you; or if we get imaging and we see that it’s spread to other areas, it may be later stage. But for squamous cell skin cancer, it’s earlier stage depending on the size. Sometimes when we get a biopsy, and in the biopsy, if we find high risk things in the biopsy, that may actually put you at a higher stage, even if the cancer is somewhat small.  

So, that could be like a stage III. But if at any point we find on imaging that the cancer has spread elsewhere – so, like you have a cancer that has spread to your liver, or to your lungs, or to the bones in your body, that’s a stage IV. 

Katherine:

Okay. And when is the cancer considered advanced? 

Dr. Park:

I think the cancer would be considered advanced if it’s not something that a surgeon can simply just remove. So, the dermatologist cannot just do a standard Mohs surgery, or the head-and-neck surgeon cannot just do a standard surgery, because advanced means that the cancer is either pretty deep, pretty large; or the surgeon can do surgery, but that means that the surgery would be very disfiguring. Sometimes these lesions can be really big on the face. 

And sure, the surgeon could do the surgery, but if we have to take part of your eye, or part of your nose or your ear, and you have to have major reconstruction, that’s considered probably more of an advanced tumor.   

Katherine:

Okay. As I mentioned, in this webinar, we’re focusing on advanced cancer. So, what is the typical treatment path for someone who’s been diagnosed at this stage of disease, at the advanced stage?  

Dr. Park:

Yeah, so, before – and I really love this question, because in the past, we did not have that much to offer patients except surgery, and then they would get a very extensive surgery. They would get reconstruction. But sometimes it’s hard to get reconstruction after a really major surgery, because you have to heal, and you have to get better. And then, after the surgery, you would typically get radiation to try to prevent the cancer from coming back. But nowadays, we have immune therapy.  

So, immune therapy is a certain type of IV medicine that’s not chemotherapy that works really well for squamous cell skin cancer. And so, nowadays, we can actually give this to you before surgery. So, we can give you a couple of doses of this IV immune therapy medicine before surgery, and really shrink your tumor quite dramatically.  

And then, that makes the surgery a lot easier, smaller. And then, sometimes after we do the surgery, and then we look at what the surgeon has taken out under the microscope, we can’t see any tumor left. And that’s really amazing, because then sometimes we don’t even need to do radiation. So, not only did we make your tumor a lot smaller, sometimes we completely made it go away.   

And then, if that happens, sometimes we don’t even need to do radiation. So, it really helps the patient. And I think this is really important, because this is somewhat newer data, and I still see patients that get referred to me for just surgery. 

But I think a lot of head and neck surgeons are now aware of this data. And so, this is something that’s, I think, becoming more common.  

Katherine:

What about targeted therapies?  

Dr. Park:

So, targeted therapies are, I think, mainly used in basal cell skin cancer. So, targeted therapies are typically oral medications or pills. They’re called targeted, because they’re used in cancers that have a specific target. So, for example, the basal cell skin cancer, the target is the hedgehog pathway, because the hedgehog pathway is abnormal. And so, these pills, they specifically target the hedgehog pathway. But for squamous cell skin cancer, we don’t have any true targeted therapies.  

Katherine:

As patients are reviewing their options with their doctor, what questions should they be asking about their care plan? 

Dr. Park:

I think all patients should be asking, what the goal of the treatment is. They should be asking, especially if they’re being offered any type of treatment, what are the side effects? What can I expect from this, in terms of how much better will it make me? They should really ask about how often the treatments are given, because some patients have transportation issues or financial barriers, and we want to know about that, so we can help them.   

Patients should also ask about any necessary blood work that is needed. They should ask what can they do in the future to prevent a similar type of cancer happening, and just make sure that they’re talking to their families, because I think social support is really important.  

Katherine:

Yeah. I think it’s important for patients to ask how the cancer is going to impact their lives overall, really.  

Dr. Park:

Yeah, exactly, because it will affect every single aspect of your life: your social life, your family life, your mental health, your physical well-being. And so, it’s really important to know and work with your doctor on what you think you can expect now, and also in the future.  

Katherine:

Yeah. Well, how do test results impact treatment options, then? 

Dr. Park:

So, there are sometimes when we have a skin cancer that actually happens inside a gland in your face. It’s one of the salivary glands in your face. And we sometimes don’t know if it’s a skin cancer that happened on the outside and that spread to the gland inside your face, or did it actually first just start inside the gland? Because a cancer that just starts inside the gland is not technically a skin cancer. It’s a different type of head-and-neck cancer, and it’s very, very rare, and it’s treated very differently.  

So, nowadays, because we have that molecular testing, like I talked about, I see lots of patients where they have a cancer in their salivary or parotid gland. We don’t know where it came from. And so, we send it for molecular sequencing or molecular testing, and there are certain clues in the molecular testing that can tell us, oh, it probably actually came from a skin cancer.  

You just didn’t know it; or maybe it’s the skin cancer that kind of was there and went away; or maybe it was a skin cancer you had like five years ago, that you didn’t think caused any problems, but it did spread, because knowing where it came from through molecular sequencing, if it’s really hard to find out where, really impacts the treatment I may give you.  

Katherine:

Dr. Park, we’ve been hearing a lot about innovation technology, or we’ve been hearing a lot about innovations in technology. How are these advances improving skin cancer care?  

Dr. Park:

They’re approving care, because we can offer patients more minimal procedures. We can tell them you don’t need this type of other treatment, and you can have the same outcome. So, we can tell you need less treatment, and the outcomes are just as good, because sometimes more treatment is not always better. More treatment sometimes means more toxicity, more time away from family, more time away from home. Advances mean that we can keep you cancer-free for longer.  

Or even if I can’t ever get rid of the cancer, we have drugs that can keep it under control for a long time, and it stays under control, even if I stop the medicine. So, all those are really remarkable things for our patients, that we have options that can help them live healthy, full lives.  

Katherine:

How do you know if a treatment is working? How is a patient’s response monitored?  

Dr. Park:

For skin cancer, that’s pretty easy, and I think that’s one of the most satisfying things, because I can often see the cancer visibly. I don’t always have to rely on a scan, as for some patients for the cancers in their stomach or something like that. So, patients will often see a dramatic reduction in the size of their tumor, sometimes even after the first treatment I give them. And not only can we tell by looking at them; eventually, I will get a scan to compare it to the scan they had it in the first place, and we see that the tumor has gotten a lot smaller.  

Katherine:

That’s good news. What about side effects of these therapies? How are they managed?  

Dr. Park:

Yeah, so, for immunotherapy, there’s one specific side effect that we don’t find with chemotherapy, and that’s really when your body’s own immune system kind of ends up attacking the other parts of your body. And so, it can cause inflammation of other organs. And so, for patients that experience that, it can be very mild, and it can be all the way to very severe, requiring a patient to go to the hospital.  

But in all cases, we just have to tell the immune system to quiet down a bit, because it’s attacking your body. And so, the way we do that is we give the patient steroids. And so, if it’s really mild, maybe you have like a small rash; maybe we can just give you a steroid cream, or maybe we have to give you a steroid pill. But sometimes, if it’s really severe, we have to tell you to go to the hospital so you can get steroids through your IV.  

Katherine:

Okay. Beyond what has been approved to treat advanced non-melanoma skin cancer, where do clinical trials fit in?  

Dr. Park:

Clinical trials are great, because they’re the reason why we have the drugs that we have today that are working so effectively. And so, I’m really fortunate to be at a center where we offer clinical trials for patients.  

Clinical trials always fit in at any point in the journey, as long as they fit your disease. So, most of the clinical trials we have are for patients that have advanced disease, not for early stage, because the early stage patients don’t really need it; because with just simple surgery, they tend to do really well, and their cancer doesn’t really ever come back and cause issues.  

But clinical trials are really important, because they’re the only way we can study a promising treatment option; see how well it works, and if it works really well, then move it further on to hopefully help a lot of other people. And that’s why we have immunotherapy today – is through clinical trials; and immunotherapy is used for lots of cancers. 

Katherine:

It is, yes. Are there barriers to accessing trials? And if so, do you have any recommendations on how to tackle them?  

Dr. Park:

Yeah, there are barriers to trials, and I think the thing that the cancer community is really trying to work on is barriers to accessing trials if you’re from an underrepresented population in medicine. So, based on your socioeconomic status, meaning how much money do you make or what your education level is, what race are you, what ethnicity, what is your background; because we know that there’s a disparity for those individuals. And so, I think really asking your doctor, staying curious; asking them, “Could a clinical trial help me?” 

Even if you have no idea of really what trials there are, or what they really mean, you can just throw that word out; and that then, the doctor knows that you’re potentially interested, and they can actually give you the information and help you learn more about it, even if you don’t know much about it; because I think it’s still quite a black box, and we’re trying to overcome this barrier, but it’s difficult.  

Katherine:

And what about researching clinical trials online? What sites would you recommend?  

Dr. Park:

So, I have to admit that there are multiple sites, but sometimes they are not very patient-friendly. Even whenever I look at them, they are not very friendly. I think the largest repository of clinical trials is the NCI database. It’s just where every clinical trial that’s open has to be registered, and it’s run by the federal government, I believe. And because it’s not super regulated, it’s just the person working on the trial entering information, and they’re typically of a medical background, sometimes the information is not very easy to digest or understand.  

So, I think really just letting your medical team know that you might be interested in a trial, then they can help you find the right trial for you. And if they don’t have one, they can tell you other areas or other centers that might have one. You are more than welcome to go search in Google and all that, but it can be really hard, and then I don’t want that to make the patient feel that this is not for them.  

Katherine:

Right, right. Are there any recent research highlights that you could share with the audience?  

Dr. Park:

Yeah, so, one thing that just recently came out is that – so, squamous cell skin cancer is actually a lot more common and a lot more aggressive in patients that have an organ transplant. So, I’m talking about patients that have a kidney transplant, or a liver transplant, or heart transplant.  

But the problem is, I can’t really give them immune therapy like I can somebody else that does not have a transplant, because like I said, sometimes one of the side effects of the immune therapy is that it can attack other parts of your body. And so, for patients that have an organ transplant, one of the risks, if I did give them immune therapy, is that it would actually attack their organ that they got from somebody else.  

And except for kidney, because we have dialysis: if I injure that organ, I don’t really have much else, and that does not bode well for the patient. But now, they’re trying to really figure out ways we can actually combine immune therapy with steroids in different doses to really see: can we actually help the patients that have organ transplants? Can we help their skin cancer? But then, can we also not injure their organ? And so, that’s something that a lot of research is being conducted on right now, and it’s really exciting.   

That’s great information. Well, Dr. Park, as we wrap up, what would you like to leave the audience with, in terms of the state of advanced non-melanoma cancer care?  

Dr. Park:

Yeah, I think as a patient, no matter your background, I think it’s just really important to be your own best advocate. And sometimes, that’s easier said than done. Some patients have families that can be advocates for them; but if you are by yourself, you can ask your doctor anything. You have the right to know, because it is your health and your body, and we do want to hear from you, because we do want to work with you to provide the best care that we can for you. 

Katherine:

Dr. Park, thanks so much for joining us today. I really appreciate it.  

Dr. Park:

Thanks so much, Katherine. It was a pleasure. 

Katherine:

And thank you to all of our collaborators. If you’d like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready, and don’t forget to take the survey immediately following the webinar.  

It will help us as we plan future programs. To learn more about advanced non-melanoma skin cancer, and to access tools to help you become a more proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us.  

Advanced Non-Melanoma Skin Cancer: What Do You Need to Know About Evolving Treatment and Research

Advanced Non-Melanoma Skin Cancer: What Do You Need to Know About Evolving Treatment and Research? from Patient Empowerment Network on Vimeo.

Treatment options for advanced non-melanoma skin cancers—such as squamous and basal cell carcinoma—are evolving quickly. Dr. Diwakar Davar shares an update on emerging research, discusses current treatment options, and provides tips for partnering with your team on care decisions.

Dr. Diwakar Davar is the Clinical Director of the Melanoma and Skin Cancer Program at UPMC Hillman Cancer Center. Learn more about Dr. Davar.

Download Guide

See More from Evolve Non-Melanoma Skin Cancer

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An Expert’s Perspective on Advanced Non-Melanoma Skin Cancer Research

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Expert Advice for Newly Diagnosed Advanced Non-Melanoma Skin Cancer Patients

Expert Advice for Newly Diagnosed Advanced Non-Melanoma Skin Cancer Patients

Advanced Non-Melanoma Skin Cancer: Who Is on Your Healthcare Team?

Advanced Non-Melanoma Skin Cancer: Who Is On Your Healthcare Team?


Transcript:

Katherine:

Hello, and welcome. I’m your host, Katherine Banwell. Today’s program focuses on helping patients with advanced non-melanoma skin cancer. We’ll review treatments, and research, and share advice for getting involved in care decisions. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to a program resource guide. If you haven’t already, click that link to access information to follow along during the webinar.  

At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars. Finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice.  

Please refer to your healthcare team about what might be best for you. Let’s meet our guest today. Joining me is Dr. Diwakar Davar. Dr. Davar, welcome. Would you please introduce yourself? 

Dr. Davar:

Katherine, thank you for this invitation. My name is Diwakar. I’m a medical oncologist and I’m the Clinical Director of Cutaneous Malignancies and Melanoma at the University of Pittsburgh’s Hillman Cancer Center. My practice largely focuses on advanced skin cancer, including both melanoma and non-melanoma skin cancers. I also direct the translational research laboratory focusing on drug development. I’m glad to be able to contribute towards this program. And, I’m happy to answer any questions that you and your colleagues might have. 

Katherine:

Well, thank you so much for taking time out of your schedule to join us today. 

Dr. Davar:

Sure. 

Katherine:

Today, we’re focusing on the most common forms of advanced non-melanoma skin cancer. What does it mean to have advanced non-melanoma skin cancer? 

Dr. Davar:

Sure. “Non-melanoma skin cancer” is actually a very broad, heterogenous term and includes patients with cutaneous squamous cell carcinoma, which is actually the commonest cancer in the United States with approximately 1 million cases a year, the vast majority of which are actually not necessarily, particularly serious or deep but do indicate predisposition towards further cancers and exposure to carcinogenic ultraviolet light. 

It also includes the entities of Merkel cell carcinoma as well as basal cell carcinoma. These common cancers ranging from very common cutaneous squamous cell carcinoma to the least common Merkel cell carcinoma and basal cell in between are primarily seen in Caucasian patients. There is a predisposition towards these cancers we discovered in patients who are older, and certainly there is a predisposition in finding these cancers in certain anatomical regions such as the head and neck areas. Most of these cancers happen in older Caucasian patients, typically above the clavicle in the head, neck, around the ears, and on the cheeks and the face. 

Katherine:

Why is that?  

Dr. Davar:

Well, the primary etiologic agent driving carcinogenesis in these cancers is ultraviolet light.  

Again, the vast majority of ultraviolet light exposure happens to people before the age of 12, and it happens predominantly on the head and neck because that is the area that is most exposed to the sun. The cancer takes a while to form because the carcinogenic effects take a while to cause the cancer. So predominantly, patients, as they start hitting their 70s and 80s, it becomes increasingly common and occasionally, these cancers can actually end up being serious and start causing advanced cancers.  

Dr. Davar:

You know, in most cases, the definition of what is considered an advanced cancer is stage IV disease. If you have lung cancer, advanced lung cancer is stage IV cancer that has spread to the opposite lung, or to the brain, or the liver. 

If you have advanced melanoma, it is cancer that has spread to a distant organ such as the lung, the liver, or the brain. Skin cancer is very, very different. Because of its unique anatomical location, even a large tumor that potentially can be cut out but hasn’t necessarily spread can still threaten vital organs. You can have a 3 cm tumor near the eye that is threatening the globe. If it is not shrunk, the surgical resection of this tumor will potentially involve removing the eye.   

Similarly, you can have a very large tumor that is not necessarily spread, but is involving the right side of the cheek near the jaw. In which case, the potential surgical removal of this tumor would involve the extremely disfiguring surgery of jaw removal, what is known as mandibulectomy.   

Given the nature of these tumors and the location of these tumors, the definition of locally advanced for this particular cancer has started to incorporate more elements of the location and the ease of which the cancer can be removed, which is very distinct from cancers in other locations, and also the proximity of these cancers to critical structures such as the nose, the lips, the eye, as well as critical vascular and neurovascular structures in the neck, such as the carotid artery, the internal and external jugular veins, and the vagal nerve bundle. 

Katherine:

What approaches are currently available to treat these more common forms of advanced non-melanoma skin cancer? 

Dr. Davar:

Right now, the most common mode of treatment is typically treating cancer that is localized.  

Again, even with the extremely increasing incident of these cancers, the vast majority of cancers that we detect are still localized and are amenable to easy surgical eradication by a trained dermatologist or a trained mole surgeon. A trained dermatologist, a trained mole surgeon, a plastic surgeon, these are commonly the physicians that encounter these patients. Surgical removal is still the primary mode of eradications of these lesions. However, increasingly, there is a role for early systemic therapy and local regional therapy to improve patient outcomes for reasons that we can talk about. Still, the vast majority of patients are still treated surgically and then increasingly, there is the role for referral to medical oncologists and radiation oncologists to talk about alternative forms of treatment that may be needed after that. 

Katherine:

What sort of alternative therapies? Are you looking at targeted therapies? Immunotherapies?  

Dr. Davar:

The primary reason for which advances have happened in this disease is really the advent of effective systemic immunotherapy and the spillover of immunotherapy into the patient landscape in these diseases. The reason for that is as follows. Immunotherapy essentially is most effective in tumors that carry a high tumor mutation burden. For example, melanoma has a tumor mutation burden on average of about 15. And the tumor mutation burden in melanoma is driven by the fact that melanoma, cutaneous melanoma is an ultraviolet light-driven skin cancer.  

However, non-melanoma skin cancers have tumor mutation burdens that are many, many magnitudes higher than that of melanoma. For example, the median tumor mutation burden in cutaneous squamous cell carcinoma is 50. Melanoma is 15. The median tumor mutation burden in cutaneous squamous cell carcinoma is three times that of melanoma. Similarly, for Merkel cell carcinoma. A large majority of Merkel cell carcinoma is caused by an unusual virus known as a Merkel cell polyomavirus. Both the viral driven tumors and the non-viral driven tumors have high tumor mutation burdens, and the same is true of basal cell carcinoma because of ultraviolet light exposure.  

The primary reason why immunotherapy has gotten a foothold in these diseases is because the underlying etiologic agent that drives carcinogenesis, ultraviolet light for the majority of these, and the Merkel cell polyomavirus for the subcategory of non-melanoma skin cancer that is Merkel are both associated with a response to immunotherapy.  

As a result of that, immunotherapy, anti-PD-1 immunotherapy is now standard of care for patients with tumors that are either locally advanced undissectible or locally advanced and/or metastatic, that is, that they have spread. They are now available for use and FDA-approved for this indication in both Merkel, basal, as well as non-melanoma cutaneous squamous cell carcinoma. 

Katherine:

Dr. Davar, now that we understand approved approaches, can you walk us through ongoing research and developing treatments that patients should know about? 

Dr. Davar:

Yeah. Now, if you think about it, the vast majority of patients with, say, cutaneous squamous cell carcinoma is presenting with large tumors involving the areas of the head and neck region. The average tumor size is approximately 1 to 2 cm.  

There are small groups of patients with much larger tumors and/or tumors with high-risk features. These include tumors that are either anatomically large or 3 cm, 4 cm in size, tumors that involve critical locations, such as the bone, the skull table, the jaw, tumors that are very close proximity to critical structures such as the eye, or tumors involving lift nodes in the neck. 

In these patients, recent work by many groups including ours has demonstrated that perioperative immunotherapy improves outcomes. What is perioperative immunotherapy? In the context of melanoma and lung cancer, giving people immunotherapy before surgery improves patient outcomes. This the same drug that you would normally get after surgery, but giving it before surgery. The very same drug before surgery improves event-free survival.  

It improves the likelihood of cancer not coming back. The primary reason for that is by turning the immune system on even before you take the tumor out, you sensitize the immune system to tumor antigens, you kill more cancer, and you do that while the tumor is present because the immune system acts and recognizes this with the immune therapy acting as a vaccine. This approach has now migrated to non-melanoma skin cancer and is actually transformative, particularly given the location of these tumors which render surgery difficult.   

Therefore, in this disease, not only is perioperative immunotherapy especially transformative in terms in terms of producing dramatic response rates, the median response rate of pathologic perioperative immunotherapy is approximately a path CR rate of approximately 50 percent. In pivotal trials done by Neil Gross, the results of which have been published in prominent journals, neoadjuvant or perioperative Cemiplimab, anti-PD-1 inhibitor has shown path response rates of approximately 50 percent. 

Whether it’s given for two cycles over six weeks or four cycles over three months, this drug really dramatically reduces the tumor and improves the likelihood of the cancer not coming back. More interestingly, recent data has also shown that this affects surgical outcomes in other ways. Historically, in melanoma and lung cancer and other diseases where perioperative immunotherapy is a standard of care, we never considered the nature of the surgery. Patients still underwent the same surgery that they would’ve undergone anyway whether or not they got immunotherapy.  

However, given the dramatic effect of perioperative immunotherapy, increasingly, we are turning out attention, particularly in cutaneous squamous cell carcinoma, which involves critical structures, to the role of surgical de-escalation as well as radiation de-escalation.  

We’re trying to see if by using perioperative immunotherapy, you can give people potentially less radical surgery, make people heal faster, undergo less plastic surgical reconstruction, improve functional outcomes, and also reduce the need for radiation, particularly in the patients who have done extraordinarily well to reduce the risk of radiation-related early and long-term toxicity.  

These results, some of which are recently being presented at prominent national meetings by Dr. Zuur from the Dutch NKI. As well as Dr. Ascierto from the Italian National Cancer Institute in Naples have shown that firstly, the pathological response rates are high but very provocatively, surgical de-escalation has been achieved and is associated with good quality of life. What we are seeing here is that perioperative immunotherapy really has an increasing role. Particularly in this disease, for reasons that have to do with the unique anatomical location of perioperative cutaneous squamous carcinoma.  

Perioperative immunotherapy is also migrating to other non-melanoma skin cancers including Merkel and basal cell carcinoma. Early trials have been done. The drugs appear to be effective. However, trials are still needed to further understand the role of perioperative immunotherapy in these other two entities. However, in cutaneous squamous cell carcinoma, perioperative trials are very advanced, pivotal trials are being designed, and increasingly, this is considered a standard of care for potentially resectable patients.  

You and I have talked about the role of immunocompetent non-melanoma skin cancer but one thing that patients do not necessarily realize that if you have a solid organ transplant such as a liver transplant, a heart transplant, or a kidney transplant, the primary reason for mortality in the first one year is allograft failure. However, if you make it past three years, the primary reason for mortality is cancer, and not cancer of the lung, but primarily, skin cancer. In this instance, the reason that skin cancer is common now, on average, skin cancers in transplant patients are much more common than skin cancer in non-transplant patients.  

In fact, patients with solid organ transplants had 100-fold higher risk of developing skin cancer compared to the general population. It has to do with the immunosuppression that is used. The immune suppression that maintains allograft tolerance also reduces T cell function. 

That reduction in T cell function allows for immune escape and the development of high-risk skin cancers. The most important thing that transplant patients need to do is make sure that they see a dermatologist. Increasingly, as we discover high risk skin cancer, there have been two main approaches that have been identified that are potentially helpful. The first is investigators at two primary sites. One, Dr. Evan Lipson at the Johns Hopkins University and Dr. Glenn Hanna at Mass General Hospital have independently demonstrated, and very provocatively, that in organ transplant patients, very close titration of immunosuppression can be done to allow for the concomitant use of immune modulating therapy.  

Historically, this is a patient population for whom systemic anti PD-1 immunotherapy was technically contraindicated because the primary risk was allograft failure. What Dr. Hanna and Dr. Lipson have demonstrated is that by carefully modulating the doses of immune suppression, you can co-administer systemic anti PD-1 without allograft rejection, and these transformative results have been publicly represented by Dr. Hanna and Dr. Lipson as a paper under review in a prominent journal.  

Concurrently, work by a biopharmaceutical company has demonstrated that the intralesional administration of an oncolytic virus, a cancer killing virus known as RP1, has provocatively demonstrated anti-cancer effect in high-risk, advanced transplant-associated skin cancers.  

These data have been presented by many colleagues, including myself and others at several recent meetings. And the most recent publication of which was by Dr. Mike Migden of MD Anderson Cancer Center in a recent transplant meeting. This drug, which was injected within the tumor by direct visual injection has dramatic effect in up to about 25 percent of the treated patients without any risk of allograft rejection and/or herpes serial conversion because this is an attenuated herpes virus. These two advances have dramatically altered the potential for patients with solid organ cancers who are developing skin cancers to potentially get novel agents that would otherwise, the absence of which, potentially result in mortality. 

Katherine:

Wow. That’s really exciting news. Research often moves quickly and I think you’re just pointing this out. How can patients stay up to date with what’s going on? 

Dr. Davar:

Well, it’s very difficult. The information is moving at the speed of light in this disease. In fact, the first study of perioperative immunotherapy was done two years ago. Right now, perioperative immunotherapy is on NCCN guidelines. 

It’s not FDA-approved, but it’s a strong Class One recommendation on NCCN given the dramatic data that Dr. Gross and many of our colleagues have generated. Just in the span of three years, much has been achieved. The way to stay up to date is to read and also to seek out information from well-trusted sources. Information such as what has been generated by the Health Content Collective, information that is from WebMD and these other areas are very useful, but do check in with your providers. Please make sure your providers are up to date and do not be afraid of asking questions. No provider would ever feel insulted that you are questioning his or her judgment by asking a question.  

I often welcome patients to ask me questions about whether or not I feel like this is the best therapeutic modality. And, do ask if there is a role for novel treatments. This is particularly because when you advance, as I mentioned, at the speed of light, particularly in the context of patients who are immunosuppressed.

Katherine:

Dr. Davar, thank you for that detailed information. It is really valuable. You mentioned, a few moments ago, clinical trials. What are the benefits of participating in a clinical trial? 

Dr. Davar:

Well, the first and the most important benefit of participating in a clinical trial is that oftentimes, your team is larger. Normally, a patient has a doctor. We have a PA and we have a nurse taking care of them. When you have a clinical trial, at that clinical trial, you have three, four, five times that number of people taking care of you. There are research nurses, research coordinators, nurse navigators, and all of these people are looking over your chart helping the doctor cross check and check to make sure that nothing falls through the cracks.  

The first and the most important thing is when you enter a clinical trial, your team grows. You have a primary physician taking care of you, but he has more help and more support. That helps ensure that the best possible care is delivered for our patients. The second benefit of taking part in clinical trials is that you oftentimes have access to the latest and the greatest.  

For example, in the context of non-melanoma skin cancer that is transplant associated, these provocative approaches that are being tested, immune augmentation of immune suppression with concurrent systemic immunotherapy without causing allograft rejection, this is only available in the context of an NCI, ECTCN funded trial that Dr. Lipson is leading. If you’re not a member of one of the ECTCN sites, you do not have access to this trial. If you’re not a patient that is being seen at one of these sites, you, unfortunately, do not have access to this trial.  

The key thing here is, entering a clinical trial represents the ability, potentially, to get a treatment that potentially could improve cancer and save one’s life without causing allograft rejection. In the context of the RP1 study, you could potentially be getting a drug that doesn’t cause allograft rejection and causes cancer aggression in a significant number of patients. But again, it is not a standard of care agent. 

Entering clinical trials helps you because it allows you access to the latest and the greatest in terms of treatment modalities. But also, it allows you to receive the best possible care.  

Katherine:

You know, Dr. Davar, we often hear this term “personalized medicine.” What does it mean? 

Dr. Davar:

Personalized medicine really means individualizing the patient’s treatment for that particular patient’s tumor. No two tumors are the same. Every tumor is different just as every person is different. Therefore, identifying and crafting the optimal treatment plan really involves identifying the most available and up-to-date information about the person’s tumor and contextualizing the treatment options in that setting.  

For example, in the context of Merkel cell polyoma, the virus associated with Merkel cell carcinoma, the treatment options would certainly include checkpoint inhibitor therapy with the understanding that the Merkel cell polyomavirus status could change both the response to the treatment but also the monitoring of the treatment because there is and acid that uses antibody titers to track the disease.  

In the context of patients with advanced cutaneous squamous cell carcinoma, the presence or absence of intratumoral CD8 T cells very provocatively can affect the response of checkpoint inhibitor therapy. The key thing to understand about personalized medicine is the more information we have about your tumor, the more informed we are about not only your current treatment, but also what future treatments might be available to you if the current treatment stops working. 

Katherine:

Aside from testing, what other factors are involved when choosing therapy? 

Dr. Davar:

These factors include, particularly for non-melanoma skin cancers, the patient’s age and performance status. We do know that as patients get older, their comorbid piece changes. They have a higher risk of having concomitant second illness such as cardiac issues, diabetes, high blood pressure, cholesterol issues, strokes, and coronary artery disease.  

These diseases in and of themselves do not necessarily affect one treatment choice over another, but it may change how you treat the patient. For example, a 60-year-old patient with melanoma may be a great surgical candidate. A 60-year-old patient with squamous cell carcinoma maybe a great surgical candidate. However, an 85-year-old patient with cutaneous squamous cell carcinoma with a tumor near the eye may not necessarily be a great surgical candidate because even though the tumor could be removed, it would result in the removal of that person’s eye.  

If this person has already has got, for example, age-related issues with balance, age-related issues with difficulty and vision and depth perception, removing this person’s eye, which is a very morbid procedure, but can be done at relatively low surgical risk, could really affect this patient’s quality of life and may force you to rethink what you would do and may result in you offering this patient a different treatment modality such as upfront use of systemic therapy rather than a standard surgical approach.  

The idea is that the more information you have about the patient, the easier it is to contextualize the treatment for a particular patient and particularly in the context of non-melanoma skin cancer. Which often time happens to patients who are, on average, one decade older than patients with melanoma. Taking their age and taking their comorbid conditions is very important in determining the treatment modality and also in making individualized patient recommendations. 

Katherine:

It’s not always easy to access the latest treatments or to find a specialist. I’m wondering what the common obstacles patients face in accessing the best care.  

Dr. Davar:

Some of the major issues are access to highly specialized treatment centers. Across the entire United States, there are clearly comprehensive cancer centers where the NCIS designated these places as being areas where patient care can deliver clinical trials available.  

Oftentimes, there is the breadth of research all the way from population research all the way to clinical trials. Not everybody has access to a comprehensive cancer center. Some patients may be living in a geographical location that is remote. Some patients could be living in a location that is not necessarily remote from a comprehensive cancer center, but may have social determinants of health that make it hard for them to access these comprehensive cancer centers. The only way around this is information.  

Patients need to be able to access information in a fashion that is both trusted, and up-to-date, and secure so that they are enabled and equipped with the right information for them to be able to have informed discussions about their care with their providers. 

Katherine:

This is all such great information, Dr. Davar. As we wrap up, I would like to get your thoughts.  

How do you feel about the future of advanced non-melanoma skin cancer research? 

Dr. Davar:

I am actually extraordinary optimistic about this landscape. When I started out as an oncologist, my big focus was in melanoma. I very quickly realized that most of the excitement was certainly, while in melanoma, was being generated, it was actually spilling over into non-melanoma skin cancer and the primary reason for that is the unique patient level challenges that make this disease a difficult disease to treat. The patient age, the comorbidities, the fact that a vast majority of our patients had gotten transplants, and that resulted in a relative contraindication of the administration of the effective agents that were developed that eradicated the majority of this disease.   

What oftentimes is a challenge, what is one man’s challenge is another man’s potential cure and it’s a potential benefit in an area in which it could be studied.  

What we realize about these challenges is they actually give us opportunities and avenues for research. As we think about non-melanoma skin cancer, we realize that this is an area in which there is tremendous potential where you can potentially give people immune therapy and improved outcomes, but not just improve patient outcomes in making people live longer, but also by reducing the burden of care by reducing the amount of surgery and radiation that people need that enables people to not just live longer, but live longer and maintain their quality of life as they age, and allows them to age with dignity. 

Katherine:

Dr. Davar, it all sounds so exciting. I want to thank you for taking the time to join us today. 

Dr. Davar:

Well, thank you for having me on this lovely program. 

Katherine:

And, thank you to all of our collaborators. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. Don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs.  

To learn more about advanced non-melanoma skin cancer, and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us today.  

What Do You Need to Know About Advanced Non-Melanoma Skin Cancer?

What Do You Need to Know About Advanced Non-Melanoma Skin Cancer? from Patient Empowerment Network on Vimeo.

What information is important for you and your loved ones to know after an advanced non-melanoma skin cancer diagnosis? This animated video reviews the types of advanced non-melanoma skin cancer, current treatment options, and important advice for engaging in your care.

What do you need to know if you or a loved one has been diagnosed with advanced non-melanoma skin cancer? 

Non-melanoma skin cancer describes skin cancers that are not classified as “melanoma.” The main types of non-melanoma skin cancer include: 

  • Basal cell carcinoma 
  • Squamous cell carcinoma 
  • And Merkel cell carcinoma 

When a non-melanoma skin cancer is large and deeply invasive, it is considered advanced. In these cases, the cancer is managed by a multidisciplinary team that could include a dermatologist and surgical, radiation, and medical oncologists.  

Treatment recommendations are based on a variety of factors, including: 

  • The location and size of the cancer. 
  • Test results, including genetic test results. 
  • Potential treatment side effects. 
  • And the patient’s overall health and personal preferences. 

If the cancer cannot be treated by surgery alone, treatment options may include: 

  • Chemotherapy 
  • Radiation therapy 
  • Targeted therapy
  • Immunotherapy
  • Or a clinical trial 

Palliative care may be used in combination with these approaches to help reduce symptoms and to manage treatment side effects. 

Now that you understand more about advanced non-melanoma skin cancer, how can you take an active role in your care?  

  • First, continue to educate yourself about your condition. Ask your healthcare team to recommend credible resources for information.
  • Next, understand the goals of treatment and share your personal preferences with your doctor.
  • Consider a second opinion with a specialist following a diagnosis to confirm your treatment approach.
  • And write down your questions before and during your appointments. Visit powerfulpatients.org/skin to access office visit planners to help you organize your thoughts. Bring loved ones to your appointments to help you recall information and to keep track of important details.
  • Ask your doctor whether a clinical trial might be right for you.
  • Finally, remember that you have a voice in your care. Don’t hesitate to ask questions and to share your concerns. You are your own best advocate.

To learn more about advanced non-melanoma skin cancer and to access tools for self-advocacy, visit powerfulpatients.org/skin. 

Where Do Clinical Trials Fit Into a Non-Melanoma Skin Cancer Treatment Plan?

Where Do Clinical Trials Fit Into a Non-Melanoma Skin Cancer Treatment Plan? from Patient Empowerment Network on Vimeo.

At what point should advanced non-melanoma skin cancer patients consider participating in a clinical trial? Dr. Anna Pavlick discusses the benefits of trial participation and how the eligibility process works.

Dr. Anna Pavlick is a medical oncologist with over 20 years of experience treating patients with skin cancer and is the founding Director of the Cutaneous Oncology Program at Weill Cornell Medicine and NewYork-Presbyterian. To learn more about Dr. Pavlick, visit here

 

Katherine:

Where do clinical trials fit into the treatment plan? 

Dr. Pavlick:

You know, for me clinical trials are something that patients need to see as an opportunity. 

It should always be the first question that a patient should say, “Hey doc, what about a clinical trial?” Clinical trials provide patients with such great resources to either get a standard therapy with something extra, or to look at a novel way of using a known therapy. I think it’s something that every patient should ask their physicians about – and not everybody is eligible, or should go on a clinical trial – but it’s certainly worth asking, “Is there a clinical trial that I could participate in?”  

Katherine:

So, who might be eligible? What’s the criteria? 

Dr. Pavlick:

Well, each trial has different criteria. So, depending on the trials that are available at the institution where you’re being seen – for example, if you have, let’s say, basal cell cancer – the clinical trial may be looking at two immunotherapies as opposed to one immunotherapy. So when we do a clinical trial, there are what we call inclusion and exclusion criteria, and those are pre-determined criteria that you have to check those boxes to make sure those patients fit that particular study.  

So it’s not a random, “You can’t participate because you’re wearing a purple shirt today.” It is, “You have basal cell, but you have never had this drug that the study says you have to have been treated with this drug in order to go on to this study.” So you can’t jump from A to Z. You have to go from A to B to get to C. So, it really is just checking the boxes, making sure that patients fit whatever the deemed criteria are, and make sure they also don’t fall into the exclusion criteria. 

You know, trials will also say, “If you have an unstable medical condition –,” you know if I have a patient who’s telling me that they’re in and out of the E.R. with chest pain because the doc thinks that they have unstable angina and may need a stint – well, that’s not a patient that you want to put on a clinical trial at that point in time. Not to say that it can’t be re-explored at a different point, but people with active other medical issues just add to the complexity of being able to determine what are the side effects, and what are the not – what’s related to study drug, and what’s related to underlying problem?  

How Can Advanced Non-Melanoma Skin Cancer Patients Participate in Their Care?

How Can Advanced Non-Melanoma Skin Cancer Patients Participate in Their Care? from Patient Empowerment Network on Vimeo.

Dr. Vernon Sondak shares encouraging advice for patients to speak up and be active participants in their advanced non-melanoma skin cancer care and treatment decisions.

Dr. Vernon Sondak is the Chair of the Department of Cutaneous Oncology at H. Lee Moffitt Cancer Center and Research Institute. Learn more about Dr. Sondak, here.
 

Katherine:                  

Dr. Sondak, do you think a patient should consider a second opinion or consulting a specialist? If so, what would you say to them, to make them feel comfortable to do that?

Dr. Sondak:                

So, I would remind everyone – as we said earlier – advanced skin cancer is not something you can pass off. “Oh, it’s just skin cancer. Everybody gets skin cancer. It’s just minor. Just put a band aid on it.” I’ve seen people who’ve neglected these cancers for a long time, thinking they weren’t serious, or thinking that the treatments were gonna be too awful, too disfiguring, or too toxic. That’s just not the case anymore.

Everyone with advanced skin cancers should have cutting edge appropriate treatment. Cutting edge doesn’t always mean brand new. It might mean the same surgery we’ve been doing for many years. Just done properly and appropriately for that patient.

So, this is a kind of cancer that usually should be treated by very experienced teams. Especially when drug treatment is needed, often when radiation is needed, and certainly when major surgery is needed. Not just the use of the drugs, but the sequence. Which drug first? Which drug second? When is surgery appropriate? When do we do the radiation?

These are sophisticated decisions, and every patient is different. So, we strongly encourage people to go to a center that has a whole panel of different specialists. And they work and talk to each other. They work with each other, work together, talk to each other, and come up with a plan for each patient. If you just go to one doctor, sometimes – an old saying – when all you have is a hammer, everything looks like a nail. There are times when somebody says, “Well, I can do radiation.” Surgeon says, “I can do surgery.” Oncologist says, “I can do chemo, or targeted therapy, or immunotherapy.”

We want them all together, saying “Yeah, but what should we do for this patient?” That’s the goal that we’re striving for. That’s when you’re gonna be the most likely to get the most successful outcome.

Katherine:                  

Dr. Sondak, what would you like to leave patients with? Are you hopeful?

Dr. Sondak:                

We have seen the most dramatic progress in the treatment of these forms of cancer of the skin – melanoma, merkel cell cancer. basal and squamous cell cancers – in my lifetime. Progress I never ever thought I would see. We are not curing everybody, but we are curing a lot more people than we used to.

Yet I still see things about these forms of cancer on the internet that say, “Oh, this is really aggressive. This needs to be treated right away. Don’t wait. Don’t make me go get a second opinion. Have somebody deal with it.”

No. Time out. First thing, it’s better to do it right than to do it right away. Second thing, you don’t get a second chance to make a first impression, and if you go down the wrong treatment path, sometimes you can’t undo that. There is always time to stop and ask, “Am I doing the right thing? Is there somebody who really specializes in this that I should be seeing?”

But the most important advice at all, of course, is you’ve got to get the diagnosis made in the first place. So, that means you have to be willing to go to the doctor, to the dermatologist, to say, “Hey, this doesn’t seem right. It’s just not healing. It just keeps getting worse. What’s going on?”, and then have to be willing to follow up and go through treatments.

If you do, we are extremely optimistic. We are seeing progress, responses, cures that we never thought possible. So, there’s a lot of reason to be optimistic. It’s not always easy. There are plenty of side effects of all the treatments that we talked about. Including surgery, radiation, and all the drugs. But it’s not like it was even 10 years ago. Huge progress for people at any age. So, really, we really are optimistic.

A Review of Current Advanced Non-Melanoma Skin Cancer Treatment Options

A Review of Advanced Non-Melanoma Skin Cancer Treatment Options from Patient Empowerment Network on Vimeo.

How is advanced non-melanoma skin cancer currently treated? Skin cancer expert Dr. Vernon Sondak reviews advanced non-melanoma skin cancer treatment approaches.

Dr. Vernon Sondak is the Chair of the Department of Cutaneous Oncology at H. Lee Moffitt Cancer Center and Research Institute. Learn more about Dr. Sondak, here.
 

Katherine:                  

Yeah. Let’s turn now to the treatment options for advanced disease. What approaches are currently available to treat advanced non-melanoma skin cancer?           

First and foremost, we always think about, can this thing be entirely removed? Can we get the cancer out and cure the patient once and for all with an operation?

Most skin cancers have not yet spread to the lymph nodes or beyond, even when they’re advanced. So, it follows that if we can remove every last cancer cell from that site, we can cure that patient. That is obviously a worthwhile goal.

But these skin cancers occur in places where a big enough surgery to remove all the cancer can be a pretty deforming surgery. It’s why plastic surgeons get involved a lot. But it’s also why we try combinations of therapy to see if we can get by with less surgery, less radical surgery. Perhaps by adding radiation or adding drug treatments to shrink the cancer.

So, surgery first. Can we do it? Can we just fix this once and for all with surgery and get it done? Whether it’s Mohs, for more advanced cases, usually a general anesthesia type surgery. Often with a skin graft or other kind of plastic surgery reconstruction. Could we just get it all out and have the pathologist tell us, “This is done. This is taken care of”? It’s not a guarantee. There’s no guarantees in this business. Only in the muffler business.

But the odds are good if the pathologist tells us the margins are completely negative. If the pathologist tells us the margins are close here, or positive there, and we don’t think removal of additional tissue is wise, then we may call in the radiation oncologist and say, “Let’s give radiation.” Kill that area where there was a positive margin and give us a margin of safety around the surgery.

In the minority of cases, we say, “This is too big to even tackle with surgery – at least at first – or two widespread. So, we’re gonna use drug treatments. If it shrinks, we may use radiation for surgery later. But first, drugs and let’s see what happens after that.”

So, today we have really three main categories of drug therapy. In the old days we had – and it wasn’t that long ago – we had really one category. I’d say that’s only been in the last – not even – ten years that we’ve had multiple options. But let’s go back 10 years.

Chemotherapy. Standard chemotherapy that people think about with cancer. Hair falls out, nausea as a prominent side effect, suppressing of your immune system, suppressing of your blood counts. That form of chemotherapy was really the only drug therapy we had for advanced melanoma. I mean, advanced non-melanoma skin cancer. Advanced melanoma too could years or more ago.

Now, through progress with melanoma, we have drugs that work in the other kinds of skin cancer. Immunotherapy took the world by storm. It worked so well for melanoma that we tried it in squamous, and merkel cell, and even basal cell cancers, and also saw great results. Now immune therapy is approved in all three of those types of non-melanoma skin cancer.

But there are problems with immune therapy if you have an altered immune system. Especially if you have a kidney transplant, or liver transplant, heart transplant, and we boost your immune system, we run a serious risk of rejection. It isn’t a guarantee, and it can sometimes be managed with additional medications. But it’s something that we have to be very, very, very cautious about, is using immune therapy in someone with a transplant.

So, targeted therapy works when we have a genetic abnormality in a cancer, that we know is only in the cancer, and that we have a drug that can block. For melanoma, if it has a BRAF mutation, we have targeted therapy drugs that target the BRAF mutation.

But non-melanoma skin cancers don’t have BRAF mutations. Squamous cell cancers don’t have mutations that today we can target. Only basal cell cancer, along with melanoma, has a mutation that we can target.

But unlike melanoma – where only some melanomas have the gene mutation in BRAF – basal cells, all the cancers have a mutation in the hedgehog pathway. You can’t pretty much have a basal cell cancer without having a mutation in the hedgehog pathway. Fortunately, we have pills that inhibit that pathway that we call hedgehog inhibitors. Vismodegib, sonidegib, and these drugs are very effective at shrinking even gigantic basal cell cancers.

But the problem with targeted therapy in general, compared to immune therapy, is that the responses don’t tend to last as long. The tumor will shrink very rapidly. But some of those cancer cells figure out a way to mutate further and avoid the drugs that we were using to treat them, and eventually grow back.          

Let me just correct one thing I said about targeted therapy, so I don’t leave the wrong impression. I said there’s not really mutations in squamous cell cancer that can be targeted. There is one called the EGF receptor, or EGFR, that we sometimes target with a drug called cetuximab.

It’s not used as much now with immunotherapy. But it turns out there is some targeted therapy, even for squamous cell cancers. But for basal cell, is where the hedgehog inhibitors are used much more effectively than targeted therapy in most other forms of skin cancer.

What Are Treatment Goals and Considerations for Advanced Non-Melanoma Skin Cancer?

What Are Treatment Goals and Considerations for Advanced Non-Melanoma Skin Cancer? from Patient Empowerment Network on Vimeo.

Skin cancer expert Dr. Vernon Sondak reviews current treatment goals for advanced non-melanoma skin cancer patients. Dr. Sondak discusses factors to consider when making treatment decisions, including age, lifestyle factors, and potential treatment side effects.

Dr. Vernon Sondak is the Chair of the Department of Cutaneous Oncology at H. Lee Moffitt Cancer Center and Research Institute. Learn more about Dr. Sondak, here.
 

Katherine:                          

There are so many factors that come into play when making a treatment decision, including a patient’s age and overall health. So, let’s walk through the considerations when choosing therapy for advanced disease. What are the treatment goals? What does that mean and what are the goals?

Dr. Sondak:                

It’s actually really important and somewhat underrated to think about, “What’s the goal of the treatment?” I think even doctors sometimes, certainly medical students and trainees, it’s something they have to learn a lot about. Because it’s easy to memorize all the names of all the drugs and all the muscles in the body. But thinking about, “What are we really trying to accomplish here?”

The first thing we would like to accomplish, when we can, is cure the cancer. Most of the advanced skin cancers we’re talking about are still curable. We can’t say all, but most. Even in the high stages they are still potentially curable with treatment.

So, of course, if we can cure someone, we might be more aggressive with our treatment plan. More intensive with our treatment than if we’re not intending to cure them. Why wouldn’t we want to cure them? Why would we have a different intention? We’d always want to, but there are times when we say, “Gee, the standard treatments haven’t worked. Now we have to think about what other goals? We can’t cure you anymore.”

It’s pretty rare with skin cancer. But it happens. It happens with melanoma, and it happens with basal, and squamous cell cancers, but rarely.

We can’t cure you. We can help you feel better because the symptoms that this large skin cancer – this advanced skin cancer – is causing. Whether they might be bleeding, or pain, or pressure on a nerve, or whatever it might be. If we can relieve that, that’s palliation. That’s relieving symptoms. There are times we say, “We want to prevent that symptom from happening in the first place. If we don’t remove this, this is gonna start bleeding, or it’s gonna press on the nerves.”

So, even if we can’t cure you, we might want to treat one or more spots to prevent symptoms from occurring. Only in the most extreme, end of the line, kind of situations would we say now our goal is just comfort. We can no longer do anything to really alter the disease. When and how we make those decisions, obviously, they are challenging. But if you don’t start with that point, then you can’t get to the right treatment decision.

If you’ve got a patient who’s not curable, you want to do the least treatment to make them feel better or prevent them from feeling bad. Whereas if you’ve got a patient who is curable, you may be willing to justify much more aggressive treatment, if that’s what’s needed to cure them. 

Katherine:                  

How do patient specific factors, like lifestyle and pre-existing conditions, impact treatment choices?

Dr. Sondak:                

It really depends, but in skin cancer it can affect them a lot.

Number one: Lifestyle. Well, how did we get skin cancers in the first place? Whether they’re melanoma, basal, squamous? Usually, the one common denominator is ultraviolet light. Got it from being out in the sun or occasionally from being in a tanning bed. Something like that. Melanomas, and to a small extent basal cell cancers, tend to be associated with brief intermittent heavy exposure, meaning sunburns. Squamous cell cancer tends to be associated with chronic cumulative years of sun exposure. I was out in the sun all my life, I fished all the time, I was a lifeguard, what have you. That’s generalization.

A lot of overlap. But the common denominator, the common theme, is ultraviolet exposure. One thing about the sun, it doesn’t just shine on one spot all the time. It shines on lots of places. So, you may have a skin cancer here, but that doesn’t mean you didn’t get sun exposure there, or here, or anywhere else.

So, lifestyle factors. One: We can’t undo the ultraviolet exposure you already had. But we can prevent it from accumulating further. So, once a person is diagnosed with skin cancer, they really need to think about protecting themselves from the sun, avoiding sun exposure, and covering their skin, and protecting their skin when they’re in the sun. Ideally, they think about it before they got skin cancer. So, they don’t get skin cancer. Or if they get it, they get a mild, minimal, non-advanced, and easily treatable case.

But we want to make sure that once a person has skin cancer, that they recognize that their lifestyle needs to change. Cigarette smoking, unbeknownst to a lot of people, is also associated to some degree with skin cancers and a lot of other big and bad medical problems. So, we would love to alter people’s lifestyle as far as smoking is concerned. Those are the couple of key lifestyle factors that we always think about.

I think the other area that is so important in deciding about treatment is the overall health of the patient, other medical conditions that they might have, and then lastly, what the patient’s own specific concerns and considerations are.

How Is Advanced Non-Melanoma Skin Cancer Staged?

How Is Advanced Non-Melanoma Skin Cancer Staged? from Patient Empowerment Network on Vimeo.

Skin cancer expert Dr. Vernon Sondak describes how advanced non-melanoma skin cancer is staged and explains which factors are taken into consideration to understand an individual’s diagnosis.

Dr. Vernon Sondak is the Chair of the Department of Cutaneous Oncology at H. Lee Moffitt Cancer Center and Research Institute. Learn more about Dr. Sondak, here.
 

Katherine:                  

And we are going to focus today on advanced disease. So, what makes this type of cancer considered advanced?

Dr. Sondak:                

So, this also is somewhat – I won’t say controversial. I’ll just say it’s not uniformly agreed on by everybody. Not everyone means the exact same thing or has the exact same definition in their mind when they say advanced.

It’s a little different than the stage. The staging of skin cancer is mostly based on the size. So, a small skin cancer is almost never an advanced skin cancer. By small I mean less than 2 centimeters, sometimes. Depending where. Two centimeters is just under an inch.

But 2 centimeters in the middle of your face or on the tip of your nose. That’s already a pretty big problem. So, somebody might say, “Well, that’s kind of advanced.” Yes it is. But that’s not what we’re really talking about here. We’re talking about larger tumors. Tumors that have spread deeply into the tissues, or tumors that have spread and gotten to the next stages. Stage III, meaning in the lymph nodes. Or stage IV, meaning it’s spread beyond the lymph nodes, to the lungs and beyond.  

In terms of stages, in terms of stage III and stage IV, basal and squamous cell cancers, we are talking about much fewer than 2 percent of all those skin cancers. For basal cell, way fewer. For squamous cell, slightly fewer than 2 percent of all cases ever getting to a higher stage, like stage III and stage IV.

Sometimes they can be very advanced without ever spreading to the lymph nodes or beyond because they invade down into the bone. Could be on the top your scalp and invade down into your skull bone. Can be on the cheek, and invade, and follow the track along the nerves of the face. A lot of ways that the skin cancer can become advanced without spreading. But cancers that have spread are automatically considered advanced.

Katherine:                  

Right. That helps us understand the disease and how it progresses.

What Is Non-Melanoma Skin Cancer?

What Is Non-Melanoma Skin Cancer? from Patient Empowerment Network on Vimeo.

Dr. Vernon Sondak provides an overview of the types of skin cancer and defines non-melanoma skin cancer.

Dr. Vernon Sondak is the Chair of the Department of Cutaneous Oncology at H. Lee Moffitt Cancer Center and Research Institute. Learn more about Dr. Sondak, here.
 

Katherine:                  

Let’s start with the basics Dr. Sondak. What exactly is non-melanoma skin cancer?

Dr. Sondak:                

Well, it’s a great question. Sometimes we wish there was a better term, because it obviously is defining this by what it’s not, not by what it is.

Katherine:                  

Right.

Dr. Sondak:                

Melanoma is the most prevalent of the really severe skin cancers. By severe, I mean the ones with the highest chance of spreading and dying. Each year in the United States, there are close to 10,000 deaths from melanoma every year, and about 100,000 cases of invasive melanoma.

But the other forms of skin cancer, and the most common two forms of skin cancer, are basal cell and squamous cell cancers. These two cancers alone, they are about two to three million cases a year, compared to 100,000 melanoma cases.

Katherine:                  

Wow.

Dr. Sondak:                

But probably causing fewer deaths than those 100,000 melanomas. So, there are many, many more of the skin cancers that aren’t melanoma, then there are of the skin cancers that are melanoma.

In fact, there are probably more skin cancers – just if we took basal and squamous cell cancer – there are probably more of those diagnosed every year in the United States than all other forms of cancer put together.

Katherine:                  

Wow. Wow.

Dr. Sondak:                

Now in general, these skin cancers – besides melanoma – are at a low risk of spreading, and metastasizing, and killing the person if their immune system is normal. So, they have almost gotten passed off as, “Oh, it’s just the skin cancer. It’s nothing to worry about.” But when they reach a certain size, when they get to a point where we call them advanced, then now the stakes are higher. It’s not millions of advanced cases, but it’s many tens of thousands of advanced cases in the United States. Some of them do spread and some of them can be life threatening, or even lethal.