VANCOUVER, B.C. – In the clinical opinion of Dr. Mariusz Sapijaszko, treating actinic keratosis without field therapy creates a disadvantage "because this is not an individual lesion disease," he maintained at the annual meeting of the Pacific Dermatologic Association.
Actinic keratosis "is a field concept disease. I tell patients ‘the sun has not been shining only on your left temple. It’s been shining all over your face and scalp, neck, and arms. ... It’s time to start looking after your skin with sun protection and lesion-directed field therapies.’"
Dr. Mariusz Sapijaszko
An estimated 11% of all dermatologic visits in the United States are for actinic keratosis (AK) and "we worry about it because the natural course of AK lesions is unpredictable," said Dr. Sapijaszko of the Western Canada Dermatology Institute, Edmonton, Alta. It’s not easy to predict which lesions will progress to in situ or invasive squamous cell carcinomas (SCCs).
An estimated 40%-80% of cutaneous SCCs arise from, or near, an AK lesion, which supports the concept of field UV damage. AK lesions may persist, regress, or progress, depending on the patient’s immune status. Some lesions that regress will recur, from 32% within 1 year to 92% within 5 years. Progression can lead to hypertrophic AKs, in situ SCC, or invasive SCC. It can be difficult to distinguish AKs and early forms of SCC or even other nonmelanoma skin cancers, "so it’s important to treat all AKs," Dr. Sapijaszko said. Lesions that can progress to SCC include those that are hyperkeratotic, painful, have atypical features such as broader or deeper presentations, as well as those difficult to clear with standard therapies and those that occur in immunocompromised patients.
Locally destructive, mechanical ways to treat AKs include liquid nitrogen cryosurgery, electrodessication and curettage, and excision. "All of these treatments are highly operator dependent, because clearly if you use liquid nitrogen cryotherapy enough you will destroy that lesion but you will not destroy the surrounding DNA damage that has been present," he said.
Field-directed therapies, however, provide an opportunity for a more complete treatment effect. Options include 5-FU (5-fluorouracil), imiquimod, ingenol mebutate, and photodynamic therapy as well as chemical peels and laser resurfacing. Chemical peels and laser resurfacing "have less robust data, but they’re operator dependent, because you can do laser resurfacing with 100 microns or 300 microns," Dr. Sapijaszko said.
"That can depend on the technique you use, and the laser you use, and the patient in front of you." Some of the field treatment options are easier to apply than others. For example, 5-FU is applied twice daily, while imiquimod is applied twice weekly; yet all boast complete clearance rates in the 40%-50% range. "Side effects are also similar between these agents," he said. "Pain is not a big issue except with 5-FU; some patients experience a significant burning sensation."
The newest approved field therapy option, ingenol mebutate, has a dual mechanism of action: it causes cell death within 24 hours and it has been shown to reduce the number of UV-induced mutated p53 patches in mice. "This is important because we’re not just treating the lesions that we see, we want to treat the molecular changes that lead to the actual problem," Dr. Sapijaszko said. "Having decreased mutations is a huge advantage. Direct cell death leads to secondary inflammation. The immune response is characterized by cytokine release and activation of endothelial cells, leading to infiltration of lymphocytes and neutrophils, which contributes to clearance of tumor cells."
Before ingenol mebutate came on the market, investigators randomized patients with AKs to one of three treatment groups: imiquimod 5% cream, 5-FU 5% ointment, or cryotherapy (Br. J. Dermatol. 2007; 157 [suppl. 2]:34-40). Compared with their counterparts, patients in the imiquimod group fared significantly better in terms of sustained clearance of cleared lesions (73% vs. 54% in the 5-FU group, vs. 28% in the cryosurgery group (P less than .01).
"I wish we had comparative data to ingenol mebutate, but to me, of these three modalities, imiquimod stands out as the favorite," Dr. Sapijaszko said.
He went on to note that combining the available mechanical and field treatments for AK simultaneously or sequentially can lead to optimal outcomes. "Combination therapy, in particular cryotherapy, has been successfully used with a variety of topicals and has been shown to be highly advantageous, compared with placebo or to some of these agents alone," he said. "In addition, cryotherapy can be used with PDT, chemical peels, and laser resurfacing. Almost nobody in my practice gets one treatment, unless it’s a single individual lesion. Everybody gets recommendations on appropriate sun protection – just being sun smart."