Comparing the efficacy of field treatments for actinic keratosis: a critical appraisal of a randomized trial in the New England Journal of Medicine

Abstract

Aim Jansen et al. conducted a randomized trial to compare the efficacy of four field treatments for actinic keratosis (AK). Setting and design This was a multicentre, single-blind, randomized trial conducted in the dermatology departments of four Netherlands hospitals. Patients were not blinded. The investigator who evaluated the trial outcome was blinded. Study exposure This study included adult patients with at least five AKs on the face or vertex scalp. Patients were randomized to treatment with fluorouracil 5% cream, imiquimod 5% cream, methyl aminolaevulinate photodynamic therapy (MAL-PDT) or ingenol mebutate 0Á015% gel. Outcomes The primary outcome was whether patients had ≥ 75% reduction in AK count 12 months after treatment. Results In total 624 patients participated. The likelihood of having ≥ 75% reduction in AK count 12 months after treatment was significantly higher (twice as high or greater) for fluorouracil than for any other therapy. Approximately 75% of patients treated with fluorouracil experienced ≥ 75% reduction in AK count at 12 months. Conclusions Jansen et al. conclude that 1 year after treatment, fluorouracil was significantly more effective at AK reduction than imiquimod, MAL-PDT or ingenol mebutate. CommentWhat is already known?When patients have multiple actinic keratoses (AKs) in one area, a variety of field treatments can be employed to treat the entire area. There is evidence that field treatments may decrease future AK and squamous cell carcinoma development. 1,2 However, there are very few randomized trials that directly compare different field treatments to help providers and patients choose the most efficacious option. StrengthsThis is a head-to-head evaluation of four common AK field treatments. 3 Rather than an outcome immediately post-treatment, this trial's primary outcome was longer term: AK reduction at 12 months. All severities of AKs were eligible, which was not always the case in prior studies. 4 Additionally, this trial is methodologically sound and appropriately powered. Assessment of validity Internal validity Enrolment, dropout and crossoversThe enrolment rate was 53%, which, while low for a trial, is not unreasonable for a study of nonfatal skin lesions in older patients. The ages of those who did and did not participate were similar, although relatively more eligible men than women participated. Dropout and crossovers were low: approximately 6% dropped out prior to the 12-month followup, and 1% crossed over to a different therapy. RandomizationPatients were randomized 1 : 1 : 1 : 1 to the four treatment arms: fluorouracil 5% cream, imiquimod 5% cream, methyl aminolaevulinate photodynamic therapy (MAL-PDT) or ingenol mebutate 0Á015% gel. Randomization was stratified by ©

Inhibition of photodynamic therapy induced‑immunosuppression with aminolevulinic acid leads to enhanced outcomes of tumors and pre‑cancerous lesions (Review)

“…Finally, third generation photosensitizers are antibody-directed and were developed to have a strong affinity for tumor cells, causing less damage to the surrounding tissues (5,6) The clinical uses of PDT span from multiple neoplastic indications, skin disorders and ocular conditions. Considering the two-dose nature of the treatment, topical PDT is frequently favored over other field therapy options, even if reportedly less effective than other field therapy options such as 5-fluorouracil (5-FU) (13). It has been utilized for other dermatologic conditions, including psoriasis, basal cell carcinoma, verruca, and extramammary Paget's disease (14).…”