PracticeUpdate Conference Series World Congress of Dermatology 2019

Expert Outlines Nonsurgical Options for Diffuse Epidermal Field Cancerization Surgical excision risks “fatiguing” patients and may place themat higher risk for metastasis.

P atients with diffuse field cancerization of the skin are often not good candidates for surgery. Nonsurgical options for this category of condi- tions were outlined in a presentation at WCD 2019. “We all see a lot of patients who have diffuse field cancerization, and I think of actinic keratosis and squamous cell in situ as essentially the same thing,” said Chrysalyne D. Schmults, MD, of Brigham and Women's Hospital and Harvard Medical School in Boston during her presentation, attended by Elsevier’s PracticeUpdate . “There is a histological spectrum. There is a clinical spectrum. You can’t really tell the difference too well between [the two] clinically. But, oftentimes, you can tell the difference between a dermally invasive squam and epidermally limited [actinic keratosis] squam in situ. … This is something that we as dermatologists can really get quite good at: discerning with our clinical eye what looks like epidermal disease and what looks like dermally invasive disease.” For patients with diffuse epidermal disease, she continued, “if you try to approach patients like this by excising every squamous cell in situ, these patients really get fatigued. They get discouraged with their care, and sometimes they even leave care for a period of time, which is bad because then they come back with more invasive disease. … We do need to treat this epidermal field canceriza- tion, however, because this epidermal disease is a set-up for dermally invasive squamous cell cancer. “These are the same types of patients who are going to end up with squam after squam after squam, and people who get 10 or more dermally invasive tumors ultimately start to accumulate a pretty high risk of local recurrence and nodal metastasis – in our data, about a 37% risk of local metastasis, and about one-quarter of these patients will finally get a tumor that metastasizes.” Inone recent trial, 932patientswhohadexperienced two or more basal cell or squamous cell cancers in the past were randomized to 5% 5-fluorouracil (5-FU) twice daily or placebo for 4 weeks. There was a 75% reduction over 12 months in the number of

squamous cell cancers that occurred in the active therapy group, compared with placebo. This effect was seen only in the first year, however. “This points to the chronicity of this condition and the fact that we need to keep treating and retreating these patients over and over again,” said Dr. Schmults. In another recent study, calcipotriol plus 5% 5-FU given for 4 days twice a day was compared with 5% 5-FU plus placebo. Even 3 years later, patients who received the combination therapy developed fewer new squamous cell cancers and had higher numbers of tissue-resident memory T cells in their skin than those who received 5-FU alone. “It seems that by adding the calcipotriol, you’re getting some kind of longstanding increased immune surveil- lance in the skin that helps people not to get so many dermal invasive squamous cell cancers,” Dr. Schmults suggested. With regard to the treatment of superficial basal cell carcinoma, a randomized study of 601 patients compared imiquimod cream for 6 weeks with 5% 5-FU twice daily for 4 weeks and methyl ami- nolevulinate photodynamic therapy (MAL-PDT) delivered twice, 1 week apart. Imiquimod was found to be superior to 5-FU and noninferior to MAL-PDT at 3 years. “So, if you have a biopsy and you know you have a superficial basal, then go ahead and use imiqui- mod on that lesion. But when you’re talking about field cancerization of a big field of disease, it’s impractical to use imiquimod, and 5-FU performs the best for squam in situ and [actinic keratosis] anyway,” concluded Dr. Schmults. Finally, a study out of Australia demonstrated that nicotinamide 500 mg taken twice daily in 386 patients who had had at least two nonmelanoma skin cancers in the previous 5 years reduced rates of squamous cell carcinoma by 30% and basal cell carcinoma by 20%, compared with placebo. Based on these findings, Dr. Schmults said, “we are putting pretty much all our patients [with] this kind of field cancerization epidermal disease on nicotinamide.”

Dr. Chrysalyne D. Schmults

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WCD 2019 • PRACTICEUPDATE CONFERENCE SERIES