Comparing Field Treatment for Actinic Keratosis

When treating actinic keratosis (AK), 5-florouracil and imiquimod demonstrated no difference in the prevention of site-specific keratinocyte carcinoma [KC] during the short- or long-term. However, a decreased risk for any KC (not site-specific) was seen with the administration of 5-florouracil. These findings were published in the Journal of the American Academy of Dermatology.

“5-fluorouracil and imiquimod are frequently prescribed actinic keratosis treatments, but no studies have compared their effectiveness at preventing keratinocyte carcinoma in a real-world setting,” wrote the authors, led by Romain S. Neugebauer, PhD, of the Division of Research at Kaiser Permanente Northern California in Oakland, California.

In the current retrospective, longitudinal study, Neugebauer et al mined electronic health records and identified 5,700 patients diagnosed with AK who filled a prescription for 5-florouracil or imiquimod in 2007. Members of the cohort were then followed for progression to KC.

The researchers found that 5-fluorouracil was correlated with a decreased risk of developing any form of KC compared with imiquimod (adjusted hazard ratio [aHR], 0.86; 95% confidence interval [CI], 0.76–0.97). However, no differences in risk by tumor subtype were observed (squamous cell carcinoma [SCC] aHR, 0.89; 95% CI, 0.74–1.07; basal cell carcinoma [BCC] aHR, 0.87; 95% CI, 0.74–1.03), or site-specific KC (aHR, 0.96; 95% CI, 0.81–1.14). Moreover, no significant differences were found in the 2- or 5-year cumulative risk for KC in those treated with either field therapy.  

One limitation of the current study is that the researchers could not adjust for several known KC risk factors, including skin type, hair color, eye color, and sun exposure history.

“Given the burden AKs pose to the healthcare system with their high prevalence, significant cost, and potential for malignant progression, dermatologists should be aware of how available treatments compare in their effectiveness in preventing KCs,” reflected the authors.

In an interview with Cancer Network, dermatologist Jerry D. Brewer, MD, MS, professor of dermatology at the Mayo Clinic, in Rochester, Minnesota, provided a recommendation based on these findings. “Although no short- or long-term risk of keratinocyte carcinoma was identified, it would still be advisable to consider a field treatment of some sort if one has extensive actinic damage.”

AKs can progress to KC, which includes both BCC and SCC. Lifetime progression rates are estimated at between 0.1% and 20%, with the rate of malignant transformation of untreated AK during a 5-year period being 5.58%. One important goal of AK treatment is to prevent progression to KC, which can not only destroy the skin locally, but also metastasize.

If a patient exhibits multiple AKs at the same anatomical level, field treatments are advised to decrease the AK burden, as well as the risk of later AKs and KCs in the treated area. Several approaches to field treatment of AKs exist, including a gamut of topical agents and light-based treatments. Imiquimod and 5-fluorouracil are two often prescribed field-based treatments. To date, little research has compared the efficacy of topical agents in the prevention of KC.