Nonsurgical Approaches for Skin Cancer

In this interview, Dr Emily Ruiz offers a glimpse into her session, “Nonsurgical Treatments for Skin Cancer,” at Dermatology Week Fall 2023. She discusses diverse approaches, from injectables to systemic therapies, and emphasizes the importance of accurate diagnosis, treatment choice, and comprehensive care for patients with various skin cancer types. The interview sheds light on the efficacy, nuances, and evolving landscape of nonsurgical interventions, contributing to improved patient outcomes and experiences.

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 preview of what will be covered during your session at Dermatology Week Fall 2023?

Dr Ruiz: At the fall Dermatology Week, I will talk about nonsurgical treatments for skin cancers and cover a range of different treatments from injectable treatments for reactive skin cancers, to topical treatments for superficial skin cancers, to systemic therapies for advanced cancers. In addition to covering treatments, I'll also be reviewing different chemotherapy preventive strategies that could be utilized for patients who develop multiple skin cancers.

The Dermatologist: What are the key characteristics and diagnostic criteria used to help identify keratinocyte carcinomas (KCs) that may be suitable candidates for nonsurgical treatments?

Dr Ruiz: There are a lot of different key characteristics depending on what the diagnosis is and the treatment we're using for that diagnosis. If we start with the injectables I mentioned, that's for what some people call eruptive keratoacanthomas, which I usually call eruptive squamous atypia (ESA). ESA are dome-shaped papules that typically occur on the arms and legs, and some patients can form them due to trauma or spontaneously, or even in a postsurgical setting. For those tumors, doing surgery can often exacerbate the condition, and so I utilize intralesional 5-fluorouracil (FU) in those situations.

For the diagnosis of ESA, it's important to put together the histology, which usually will reveal well-differentiated squamous cell carcinoma (SCC). The clinical appearance of the lesions is small and dome-shaped, and consider the history that they either spontaneously occur, frequently on the legs and sometimes the arms, or occur in areas of trauma. Therefore, you really must use all those different pieces to make the diagnosis.

When it comes to topical therapies, I'm typically use them for superficial skin cancers, such as squamous cell carcinoma in situ (SCCIS) and superficial basal cell carcinomas (BCCs). For that, we also need to use the pathology with a biopsy showing one of those two diagnoses, but also the clinical appearance because sometimes you can have sampling errors where a biopsy is superficial and will only show a superficial skin cancer. However, in reality, there's a larger lesion that is clearly more invasive. And so, it's important to put the histology in context.

For more advanced cancers that require systemic therapy, such as immunotherapy or other oral medications, they can need a multidisciplinary team. And that's where you consider not only the tumor, the location, and prior treatments, but also the patient and what their goals are, as well as what they're able to undergo given their other comorbidities. So, it really is a multidisciplinary team that weighs in for that diagnosis.

The Dermatologist: Could you provide an overview of the different nonsurgical treatments available for KCs and their respective mechanisms of action?

Dr Ruiz: I mentioned intralesional 5-FU, which is a form of chemotherapy. However, for these reactive conditions, it's not actually the chemotherapeutic properties that we're utilizing. Some people inject steroids into these conditions. I prefer the chemotherapy in my practice, just in the off chance that we're missing the diagnosis of a more aggressive cancer. I feel that there may be some therapeutic benefit in the 1 to 2 months’ delay before we realize that.

For topical chemotherapies, we have several options. We have 5-FU, which I often combine with calcipotriene: it probably has an immunologic mechanism in this setting. So, you're simulating T cells along with the chemotherapy, which is why it works quite well. You can also use imiquimod. This is useful for superficial BCC, and that also works through an immunologic mechanism.

When it comes to systemic agents, we have several options for advanced cancers such as advanced SCC and BCC. We can use immunotherapy, particularly a PD-1 inhibitor, which blocks the PD-1/PDL-1 pathway and is being utilized in many different cancers. Another systemic agent for BCC is a hedgehog inhibitor, and that's useful in basal cells that have a patch mutation.

Additionally, I utilize a medication called capecitabine, which is an oral 5-FU. I use this for patients who have either diffused actinic damage or many SCCs, and it helps treat both of those diagnoses without needing to use topical creams.

The Dermatologist: How does the effectiveness of nonsurgical treatments compare with traditional surgical approaches in terms of disease control, cosmetic outcomes, and overall patient satisfaction?

Dr Ruiz: Sometimes I don't like to directly compare in these settings. I try to think of which treatment is the most appropriate. In terms of dermally invasive skin cancer, surgery is the gold standard and has the highest cure rates. But for superficial skin cancers, such as SCCIS and superficial BCCs, we can get excellent outcomes with nonsurgical treatments. We did a study at our institution several years back that looked at nonsurgical treatments for these diagnoses and found that the 5-year disease-free survival was 95% compared to 99% for most surgeries. Which is not as good as surgeries, but still quite high.

When I think about intralesional 5-FU for ESA, it really seems to work better because surgery just exacerbates the condition. And when you consider systemic therapy, it's not a matter of comparing it to surgery; it's just that surgery might not be an option for that tumor and, therefore, you need to do something different in those situations.

The Dermatologist: What additional tips and insights would you like to share with your colleagues regarding nonsurgical treatments for skin cancer?

Dr Ruiz: I believe that combining all our different treatment options for skin cancers can really help us optimize treatment, especially for patients who have field cancerization or develop multiple skin cancers. Understanding what other options we have besides nonsurgical treatments can help us improve outcomes, reduce surgeries, and improve the patient experience.

And a significant piece of that is chemoprevention. So, what can we do to prevent skin cancers from even forming? This is truly important for these patients. Fortunately, we have a lot of nonsurgical treatment options. It's really helpful to do frequent field treatments. You can do oral chemoprevention with nicotinamide or acitretin, and there are several other options, including photodynamic therapy. All these treatments can help reduce the actinic burden and hopefully reduce the number of biopsies needed and skin cancers that the patient develops before they even need to undergo treatment.

Reference
Ruiz E. Nonsurgical treatments for skin cancer. Presented at: Dermatology Week Fall 2023; September 20–27, 2023; Virtual.