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Olson grade, need for more treatment are markers of increased skin cancer risk in actinic keratoses

JAMA Dermatology
Reuters Health - 06/05/2022 - In patients with multiple actinic keratoses (AKs), Olson grade III and the need for more treatment were identified as markers for increased risk of cutaneous squamous cell carcinoma (cSCC) in a secondary analysis of a randomized trial.

"There is an alarming increase in sun damage resulting in AK and cSCC," Dr. Shima Ahmady of Maastricht University Medical Center in the Netherlands told Reuters Health by email. "In a population-based cohort study in the Netherlands, AK affected 49% of men and 28% of women aged 50 years and older." (https://bit.ly/3kIsNZB)

"We found that the risk of invasive cSCC was significantly higher in patients with Olsen grade III AK (AK with severe keratosis) compared to AK with mild keratosis," she noted. "In patients with Olsen grade III AK who needed additional treatment, more than a third developed an invasive cSCC within four years. Close follow-up of these patients is therefore indicated."

By contrast, she said, "Because the risk of cSCC was very low in patients with AK Olsen grade 1, follow-up might be omitted, and further studies should be aimed at investigating whether treatment is still indicated in those patients."

As reported in JAMA Dermatology, Dr. Ahmady and colleagues conducted a secondary analysis of a multicenter randomized clinical trial in the Netherlands involving 624 patients (median age, 73; 90%, men) with a minimum of five AKs within an area of 25 cm2 to 100 cm2 on the head.

Participants were randomized to 5% fluorouracil, 5% imiquimod cream, methylaminolevulinate photodynamic therapy, or 0.015% ingenol mebutate gel. The primary outcome was the proportion of patients with invasive cSCC in the target area during a median follow-up of 46 months.

Twenty-six patients were diagnosed with invasive cSCC in the target area.

The total four-year risk of developing cSCC in a previously treated area of AK was 3.7%. Risk varied from 2.2% in patients treated with fluorouracil to 5.8% with imiquimod.

In patients with severe AK (Olsen grade III), the risk was 20.9%, and was especially high (33.5%) in those with severe AK who needed additional treatment.

Among the study limitations, the authors write, "The sample size was calculated to compare 4 field-directed treatments of AK with respect to effectiveness on the reduction of AK lesions and not for comparing long-term risk of invasive cSCC. Thus, a limitation is the small number of cSCC events, resulting in low power to detect small but relevant differences in long-term risk of cSCC with significance."

Further, there were no predefined criteria for additional treatment, which was at the discretion of the treating dermatologist. Also, no placebo group was available, so more studies are necessary to determine whether treatment can be omitted in patients with low-risk AK.

Dr. Abhishek Aphale, Director of Dermatologic Surgery at Fox Chase Cancer Center in Philadelphia commented that the study "lends further support to a notion which is already widely accepted, that AKs are associated with an increased risk of development of cSCC."

"The finding that a vast majority of the cSCC lesions developed in an area clinically diagnosed as AK is somewhat helpful in supporting the notion that AK is a pre-malignant lesion capable of transformation to cSCC," he said by email. "This is significant because this notion is still in debate."

"The confounding factor here is that the original AK was diagnosed clinically, not histologically," he noted. "Therefore, it is unknown whether it was already a cSCC."

"The number of patients in the study who developed cSCC was quite low; therefore, the study lacked the power to detect differences which reached significance," he said. "Additionally, the study population was heavily skewed toward males. While it is accepted that AKs are predominantly diagnosed in men, that ratio is thought to be closer to 4:1 rather than that in this study (about 8:1)."

"A similar study with a higher number of patients with a more proportionate distribution would perhaps be more useful for application in clinical practice," Dr. Aphale concluded.

SOURCE: https://bit.ly/3MZg94R JAMA Dermatology, online April 27, 2022.

By Marilynn Larkin

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