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Karl D. Lewis, MD


Link Between Risk of Squamous Cell Skin Cancer and Severity of Actinic Keratosis?

By: Celeste L. Dixon
Posted: Monday, June 20, 2022

Especially close follow-up of patients with multiple areas of severe actinic keratosis, particularly those who require treatment beyond initial therapy, is warranted to watch for the development of invasive cutaneous squamous cell carcinoma (SCC), according to research findings published in JAMA Dermatology. Klara Mosterd, MD, PhD, of Maastricht University Medical Center, the Netherlands, and colleagues performed a secondary analysis of a randomized trial that included 624 patients, all with five or more actinic keratoses within a 25- to 100-cm2 area on the head.

Overall, 26 of the 624 patients (3.7%) were diagnosed with invasive cutaneous SCC in the target area during a 4-year follow-up period after the end of treatment. They had been randomly assigned to 5% fluorouracil, 5% imiquimod cream, methylaminolevulinate photodynamic therapy, or 0.015% ingenol mebutate gel. However, that risk rose to 20.9% in those patients diagnosed with severe actinic keratosis (Olsen grade III), and was higher still—33.5%—in the patients with severe actinic keratosis who needed additional treatment beyond the original therapy. These results confirm previous study findings “in which rapid recurrence or persistence after therapy, hyperkeratosis, and palpability were found as risk factors for cutaneous SCC in actinic keratosis,” noted Dr. Mosterd and co-investigators.

The patient cohort was primarily male (89.4%), with a median age of 73 years. The results from the intention-to-treat analysis indicated that the overall risk of cutaneous SCC was lowest in the patient group that was initially treated with fluorouracil (2.2%); the risk was 3.0%, 3.6%, and 5.8% in those treated with ingenol mebutate gel, methylaminolevulinate photodynamic therapy, and imiquimod, respectively.

“An important question that remains to be answered is whether treatment resulting in reduction of actinic keratosis lesions also results in preventing progression of those actinic keratosis lesions into invasive cutaneous SCC,” the authors pointed out.

Disclosure: The study authors’ disclosure information can be found at

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