Non-Surgical Treatment For Skin Cancer

Non-surgical treatments for non-melanoma skin cancer are expanding, but selecting the right approach requires balancing efficacy, patient preference, and risk factors. In this interview, Abigail H. Waldman, MD, FAAD, discusses key considerations for treatment selection, the role of active surveillance, and the latest advancements in systemic therapies. Learn how dermatologists can optimize patient outcomes while integrating emerging data into daily practice.

Dr Waldman is the medical director of the Mohs and dermatologic surgery center and the director of Mohs surgery at Brigham and Women's Hospital in Boston, MA. She is also an assistant professor of dermatology at Harvard Medical School, specializing in skin cancer treatment and dermatologic surgery.

Transcript:

With multiple non-surgical treatment options available, what key factors should dermatologists prioritize when selecting the best approach for a patient with localized non-melanoma skin cancer?

The things you want to consider are related to the patient. So you want to consider the patient in front of you and think about what will offer the best cure rate and also be convenient and reasonable to do for the patient. So, for instance, if you have somebody who's already in the office, maybe doing a destructive modality like cryotherapy might be more beneficial because it's sort of a one and done type of thing. Whereas if you have somebody far away, sending them a prescription for a cream like five flu or UIL might be a much more reasonable approach for non-melanoma skin cancer. The other things you want to consider in general are should they use a non-surgical approach or a surgical approach. And that's a lot of what our discussion is about. And a lot of it has to do with what are the risk factors for complications during surgery. So any sort of treatment modalities is going to be a conversation between you and your patient.

Active surveillance is gaining interest in select cases. What criteria should dermatologists use to determine which patients are appropriate for this approach, and how do you counsel them on risks and benefits?

So, I often will use active surveillance when the patient just really does not want surgery, and they have a very low risk tumor. And by low risk tumor, I mean something that's in very superficial, maybe a very small basal cell carcinoma in an area that's not really at risk for deformity if it were to grow. So those are the most common times that I use just sort of a watch and wait type of approach. The other time I use it is in patients who are very elderly who have many, many risk factors that would make treatment perhaps worse than the disease. An example would be I have a patient who has a decent sized basal cell, but it's on the foot, very elderly, 98 years old, has a lot of cardiovascular risk factors and bleeding risk factors. And we basically had a conversation decided that the non-healing wound that would be created on his leg after surgery would be worse than this basal cell, which was not really bothering him all that much.

So those are type of monitoring. I tend to also required that the patient's pretty good at following up and communicating if things are changing. And I stress that pretty strongly. If it changes, if it grows and that if you're having symptoms, please do call. And generally, patients that are willing to follow up definitely helps sort of that trust that we can just sort of monitor.

For patients who may be averse to surgery due to comorbidities or personal preference, how do you set expectations regarding efficacy, recurrence risk, and cosmetic outcomes with non-surgical treatments?

Try to be very truthful about the cure rates. I say, oh, you have a superficial skin cancer. The good thing is you actually have a few different options and I'll say, I'll kind of open with the best cure rate is MO'S surgery for this. That being said, there's a risk of bleeding, there's a risk of infection, there's a risk of complications. And on the other hand, we have a topical treatment we could use not as good of a cure rate, but you can help avoid some of the complications associated with surgery.

And then usually I'll kind of leave it up to the patient and to help them decide. I'll say, if this is something that's keeping you up at night and you don't want to do sort of a longer treatment, we should do surgery. If this is something you'd really like to avoid those complications, then we should pick a non-surgical option. So that helps them get into the mindset of like, well, what is a priority for them? Is it curate or is it complications and risk factors like bleeding and poor wound healing and things like that. And then patients are usually pretty smart about identifying really what is most important to them. And so by sort of couching in that way, I kind of just help them make the decision a little bit. And if I feel strongly one way or another, I will say there is a process.

With advances in systemic therapies, particularly for patients with high tumor burden or eruptive keratoacanthomas, how should dermatologists integrate these options into their treatment strategies?

It usually is on the legs where patients will get many, many skin cancers, squamous cell carcinomas usually on the lower leg, but they can be elsewhere. And they tend to happen in kind of an eruptive pattern and sometimes even what's called koebnerizing, meaning they show up in areas that have been damaged or have had surgery. So you'll do surgery on a skin cancer and then all of a sudden four will pop up in the area. And it's hard. You have to say, well, is this just an aggressive tumor that is coming back very fast or is it more of this sort of reactive process that's not really skin cancer, even though it can look like it on pathology. And it has different names that it goes by and it's a little bit of a clinical picture versus a pathologic picture. So, for those lesions where patients will suddenly get 6 or 10 of these eruptive paths, that is usually the best.

I mean, obviously you can surgically remove them, but then that's a lot of surgeries. But usually what we will do is intra lesional five floor UIll, so IL-5 FU and the treatment, they come in and we numb them first and then we inject this 5-FU and turns into a little bit of a blister. Sometimes they need more than one treatment, probably average is about two or three, and then they typically go away. There is also intralesional methotrexate that is also effective in treating these lesions as well. And sometimes if they have very small ones, we'll actually use topical 5-FU under occlusion, meaning under saran wrap or under UNA boots or something like that to help get rid of these very little eruptive kass.

The biggest advancement I think, in systemic therapy for high-risk skin cancer would be the PD-1 inhibitors. The checkpoint inhibitors like cemiplimab, those are very effective for very high-risk skin cancers. And they can be used adjuvantly, meaning after surgery they can be used in place of surgery or neoadjuvantly before surgery. And in terms of the neoadjuvant setting, oftentimes it's to shrink the tumor so that it can be become surgical candidate. So it tends to be used for skin cancers that are very high risk 8 or higher. So they tend to have very high risk features. They tend to be large, larger than a quarter for sure. And even larger, they tend to have perineural invasion, lymphovascular invasion depth that's beyond the fat, and oftentimes poor differentiation or multiply recurrent. So they tend to be high risk skin cancers. And then that in cases where either we would say this patient's not a surgical candidate, so they need another option. And a PD one inhibitor works quite well, but it's not a hundred percent, it's more like a 50% clearance rate, complete clearance.

And then, like I said, sometimes we use it neoadjuvantly where we'll treat for a few treatments and then see if that patient becomes a surgical candidate. And then oftentimes we will also use it afterwards for very high risk in cancers, even if they have clear margins, it can be used in cases where we really want to do the most to keep it from coming back. There are other medications that can be as well in that setting. Sometimes certain medications are used with radiation in those cases to reduce the chance that it comes back. And so those are the most common ways that we use those systemic medications. Now, things you need to take into account is your patient a transplant patient because these medications can increase risk of transplant rejection. And so that's something to consider. Sometimes they're still used in certain instances, but definitely plays a role in decision making.

Are there any emerging data or new clinical pearls that you believe will refine how dermatologists’ approach non-surgical management of non-melanoma skin cancer in the coming years? 

So, I would say that the data that's coming out, there's just for the first time, a letter to Jad that was just published from Brigham and Brown, showing that you can use combination calcipotriol 5-FU as a very effective short course topical for superficial skin cancers like superficial basal cell and squamous cell carcinoma and situ. So all the data prior had been in actinic keratosis. So this is the first evidence that it's effective with over a 90% clearance rate for these low risk skin cancers of the head and neck and other high risk sites, I would say. And so I know that there's a clinical trial ongoing at Boston University, and I do suspect some other papers will come out on this topic, especially after completion of that enrollment of that trial. So I think more and more is going to come out in the next year or two about the use of these short-term treatments. And why that's interesting is just that a lot of times the reason these topicals fail is not because they fail necessarily, but because the patient doesn't complete a course. It's hard to do something twice a day for four to six weeks or even longer. And so the shorter courses, which are five to 10 days might be more effective because patients will actually be able to comply.

Is there anything else you’d like to share with your colleagues regarding non-surgical treatment for skin cancer?

I think just really, you're going to get a lot of questions. I think patients are becoming more and more educated about their options, and I think a big one that's being advertised to them is superficial image guided, superficial radiation therapy. And I think just really knowing how to answer the questions when your patients ask you about it and what the pluses and minuses are, and I'll be talking about it in this talk, but I think just knowing who it's appropriate for and what the downside might be is important because unlike some of these other nonsurgical treatments, the image guided superficial radiation therapy is being actively advertised to them. So they hear about it because they see billboards, they see it online, they see it on their Facebook feed. I mean, it's something that's going to come up more and more. So I think that's where just educating yourself and knowing how to help patients make those decisions.