Topical Therapy for Treating Squamous Cell Carcinoma in Situ

In this interview, Dr Emily Ruiz discusses her session, “Pro and Con: Contentious Concepts” at the 2023 ACMS Annual Meeting. She covered the topic, “Mohs vs Topical Therapy for Squamous Cell Carcinoma in Situ (SCCIS): Pro Topical Therapy.”

Emily Ruiz, MD, MPH, is an associate physician at the Mohs and Dermatologic Surgery Center of Brigham and Women’s Faulkner Hospital in Boston, MA. She is also an assistant professor of dermatology at Harvard Medical School in Boston, MA, and director of the High-Risk Skin Cancer Clinic at Dana Farber/Brigham and Women’s Hospital in Boston, MA.

The Dermatologist: Can you give us a recap of what was covered during your session at the 2023 ACMS Annual Meeting?

Dr Ruiz: In the pro and con of contentious concepts, I presented on pro topical therapy for cutaneous SCCIS. This was part of a session where different topics were presented and 2 people took the counterargument.

The Dermatologist:  What are the advantages of topical therapy over Mohs micrographic surgery when it comes to treating SCCIS?

Dr Ruiz: There are a number of different advantages. One of the big benefits is that topical therapy is nonscarring and so it is nice for small lesions or cosmetically sensitive areas, but it also works well for larger lesions.

We treat even large plaques of SCCIS with topicals and it clears nicely and leaves no evidence of scarring. It was interesting, during the same session of contentious concepts, someone [Dr Seaver Soon] presented on pro superficial radiation therapy and showed a number of examples of superficial radiation for SCCIS. And 1 of the big things he was saying was how nice it heals, but there was still some scarring, but also there was a lot of alopecia from the radiation.

And what is great is that this does not leave scars and it does not cause hair loss and so patients are happy with that. It is also nice because for SCCIS, this can be a field effect. Sometimes you will get clinical changes in 1 area, but the surrounding tissue will have subclinical findings on biopsy and so you can preemptively treat the lesion that has been biopsied, but also the areas around it that might develop into a clinical SCCIS in the near future.

You are addressing issues before they become a problem. It is also great in areas that are difficult to heal, such as the lower leg where there can be edema and since it does not leave a wound that needs to be healed, it can work well in that instance.

Something I did not get to discuss at the meeting was I also sometimes use it after surgery. Sometimes we see on our Mohs margins a lot of actinic keratosis (AK) or SCCIS and instead of removing the SCCIS with Mohs, which can create a much more extensive wound, I take out the invasive component, repair it, and then I will use cream to treat the rest of the SCCIS after it is healed up. And there have been some studies showing that, because SCCIS has this subclinical extension on Mohs, it is more aggressive. I really do not view it that way. I think there is a field effect, and you can treat that with creams rather than trying to chase what looks to be normal skin.

The Dermatologist: Are there any limitations to using topical therapy for SCCIS? If so, what are they?

Dr Ruiz: The biggest limitation is that you cannot always be sure that there is nothing deeper underlying the SCCIS. Biopsies are only partial, and the biggest concern is that there could be a more significant lesion that you are not capturing.

It is important to make sure you are selecting it in the appropriate setting. Do not trust just the biopsy, you want to make sure that correlates with the clinical, but also ensuring that it resolves. Especially with larger lesions, what I always tell patients is even if the whole thing does not resolve, we are going to shrink it down and the surgery will be much smaller, but we do want to make sure that it completely resolves.

And if it does not, that is when I do want to go back and do some biopsies. For patients who just have a lot of skin cancers or a lot of precancerous and SCCIS, it is nice to clean them up with the cream and then it helps to highlight the areas that are not going to go away and that you do need to pay further attention to. I find it sometimes hard to focus in on those areas when there is just so much going on.

The Dermatologist: How effective is topical therapy in treating SCCIS compared with Mohs micrographic surgery?

Dr Ruiz: The data are a bit limited. I covered in the session that a lot of studies done have very short follow up, less than a year. You are not really looking at long-term efficacy and they are in very small patient populations. My colleague here at Brigham and Women's published a few years back our experience with nonsurgical modalities for SCCIS. The majority were treated with fluorouracil twice a day for 4 weeks, but a minority did get imiquimod, ingenol, or cryotherapy.

And we found that at 5 years, there was no recurrence in 95%. That was a very good result compared to 99% of the Mohs group. But still 95% is comparable to a standard excision. Upfront I tell patients that in our hands about 95% of the time these will not come back in 5 years. I do tell them that Mohs would be 99%, but most patients still then opt for the 95% odds with the topical therapy.

The Dermatologist: Can you discuss any potential risks or side effects associated with topical therapy for SCCIS?

Dr Ruiz: When we discuss this with patients, we show them photos of patients who have used topical therapy because the expected response is to get very red, irritated, and depending on the degree of actinic damage you can even get bleeding. I have patients who will come in and say, “I can't use that cream because I'm actually allergic to it,” because they have used it before and gotten red and irritated.

So, I ask about the allergy, and they just have the expected response. It is important to go through with a patient what the anticipated response is. Again, like I said, we show them pictures because if they are aware of what is going to happen, they are more likely to be compliant with it. And then they also can appropriately select the right time to do the cream if they have upcoming events.

That is the biggest side effect. There are some other much less common ones. You can get superinfection with bacteria or viruses, which does not happen very often, but can be managed. Even more rare is the possibility of having a systemic reaction if you have a deficiency in a certain enzyme. But this is quite rare and we do not test upfront for that enzyme deficiency.

The Dermatologist: What factors should be considered when determining whether topical therapy or Mohs micrographic surgery is the best treatment option for SCCIS?

Dr Ruiz: The biggest thing is first determining, “Do you think clinically that the pathology matches with the clinical assessment?” If I think that it looks superficial, then I go ahead and treat with topicals. I treat topically, even if there is adnexcell extension. I do not find that reduces the response. And I also do treat immunosuppressed patients this way.

My first recommendation to a patient if they have an SCCIS, regardless of their underlying medical comorbidities or adnexcell extension, is to discuss field treatment. I always ask, “Has this been treated before?” And if they say yes, I ask when, because sometimes they will say, “I had this treated with cream 10 years ago, but it is probably not related.” But it is very different from if they just used a topical course a couple of months ago or 6 months ago, then you might want to think is there a reason this is not responding. Maybe there is not an invasive component.

I try to home in on what the recurrence is, if it really is a recurrence, and then decide whether this is someone who would be better served with Mohs surgery. Some patients just do not want to do the cream because of the reaction, or they really need that margin assessment. But I find, most of the time, when patients come in to talk to us about it, they do want to go with the topical therapy. So, at least in our patient population, it is for the most part the patient's preference.

The Dermatologist: Can you go over the key points from the session in detail?

Dr Ruiz: I think the biggest point is that for an SCCIS, you can get pretty good responses, 95%, again in our hands, at 5 years with a nonsurgical modality that does not leave a scar. In either a large lesion, or a cosmetically sensitive patient, or in an area that is difficult to heal, this is a good option and is worthwhile thinking about.

I did mention that we now use a combination of 5-fluorouracil and calcipotriene twice a day for about 10 days. This is also off label. It has only been studied in AK and it is not approved for that either, but I have been doing it for a number of years now. Using it for only 10 days rather than 4 weeks really limits the time that someone has the cutaneous reaction from the treatment. It has improved compliance in general.

Again, making sure you correlate your clinical with your pathology is important because we do not want to just treat lesions that are not appropriate if there is a more substantial underlying tumor that needs to be removed surgically.

The Dermatologist: Are there any more insights you would like to share about your session and/or ACMS?

Dr Ruiz: I think that what is always really apparent from any meeting, but especially the Mohs meeting, is there are multiple ways to do things. And it is a really great place to get expert opinions on different subject matters. It is somewhere where I go and when I leave there, I try new things.

I hope that people might put this on their radar as 1 of the treatment options and give it a shot because again, in our experience, it works well, and patients are generally happy. It can help alleviate some of the backlog we are having with removing invasive skin cancers. In our institution, we are really booked out and we have aggressive tumors that have to come off. We have multiple a week, and so it has allowed us to focus on the tumors that really need our help.

Reference:
Ruiz E. Pro and con: contentious concepts. Presented at: American College of Mohs Surgery (ACMS) Annual Meeting; May 4–7, 2023; Seattle, WA.

Watch Dr Ruiz's video interview!