Non-melanoma skin cancers are increasing

Although melanomas draw a lot of attention, non-melanoma skin cancers are also on the increase. Advances in the treatment of actinic keratosis, basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma were explained in a July 27 session at the AAD Summer Meeting in New York. Gary Goldenberg, MD, assistant clinical professor of dermatology at Icahn School of Medicine at Mount Sinai Hospital, reviewed advances during “What’s New in the Diagnosis and Treatment of Non-melanoma Skin Cancer” (U001).

Gary Goldenberg, MD: “I call this the actinic march where cells progress from being just a few mutated to actinic keratosis to in situ carcinoma to invasive carcinoma.”

Actinic keratosis

Multiple studies have shown that actinic keratosis (AK) can progress to squamous cell carcinoma (SCC), but may also be associated with basal cell carcinoma (BCC) and melanoma. One study linked follicular extension as a prognostic factor in this progression and association.

There is direct correlation in genetic mutations between AK and squamous cell carcinoma,” Dr. Goldenberg said. “I call this the actinic march where cells progress from being just a few mutated to actinic keratosis to in situ carcinoma to invasive carcinoma.”

Another study showed that in areas of excised carcinomas in sun-damaged skin with BCC, SCC, and melanoma, AK is prevalent in the surrounding tissue.

“AK may not only be a precancerous growth, but it may also be a signal that other skin cancers are more likely to occur in the area,” Dr. Goldenberg said. “It may also overload the local immune system to such an extent that other skin cancers that are not related to AK may also be more likely to occur. We believe our data has corroborated this concept.”

A successful treatment for AK is time sequential therapy, which is a concept often used by medical oncologists.

“It is therapy that is timed and controlled, and happens in a sequential fashion,” Dr. Goldenberg said. “We already have that in dermatology because multiple studies show that these drugs work best or work well when you combine them with other modalities we have.”

One combination of therapies uses cryotherapy with imiquimod or ingenol mebutate and a second combination uses photodynamic therapy with ingenol mebutate.

“If we combine destructive therapies like cryotherapy or photodynamic therapy with a topical field therapy like imiquimod and ingenol mebutate, it works better,” Dr. Goldenberg said.

Basal cell carcinoma

That approach of combining therapies is also used to manage advanced BCC, which is defined by its location, size, and if the patient previously had surgery for BCC. Two oral medications, vismodegib and sonidegib, are approved by the FDA to treat advanced and metastatic BCC. These medicines can be used alone or as adjuvant therapy with surgery.

“One of the ways we conceptually think about using these drugs is as adjuvant to surgical procedures. You can shrink a tumor with these two medications and then resect and develop a smaller scar. There is some evidence with vismodegib that you are able to do that,” Dr. Goldenberg said.

Squamous cell carcinoma

Surgery is the common treatment for SCC, and so the clinical size of the tumor is important. Tumors of 2 cm or greater have a worse prognosis than smaller tumors. Other key factors in the prognosis of patients with SCC are the depth of the tumor and SCC subtype.

“Tumors that are less than 2 mm in thickness under the microscope seem to do better than those that are 6 mm or greater in size,” Dr. Goldenberg said. “With tumors between 2 and 6 mm, there is an intermediate risk, and that risk is for local recurrence and metastasis.”

Other types of treatment that are sometimes used to manage SCC are electronic brachytherapy and superficial radiation, he said.

Merkel cell carcinoma

The incidence of Merkel cell carcinomas is increasing, most likely because they are linked to a Merkel cell polyomavirus that affects older patients with immunosuppression.

“More people who are immune-suppressed are living longer, and this may contribute to the increase in this viral-associated tumor,” Dr. Goldenberg said. “The issue we have as dermatologists is we still don’t think of Merkel cell as one of the common non-melanoma skin cancers, but studies show that we do need to think about Merkel cell more than we usually do.”

That aging population is a common thread in the increase in incidence of all non-melanoma skin cancers.

“We have an aging population that is living longer and spending more time outside without listening to dermatologists about using sun protection,” Dr. Goldenberg said. “We are going to be dealing with these skin cancers for long time. Optimizing our therapy and stressing prevention are important, as is understanding what treatments are available.”

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