International guidelines introduced for actinic keratosis

Also known as solar keratosis, actinic keratosis (AK) is one of the most common neoplastic skin lesions with the potential to progress into invasive squamous cell carcinoma (SCC). AK lesions typically occur in individuals with chronic photodamage, and are particularly frequent and especially challenging to treat in immunosuppressed individuals, such as organ transplant recipients.

Several different therapies are currently being used for the treatment of AKs, including cryotherapy, electrodessication and curettage, topical 5-fluorouracil (5-FU), imiquimod, ingenol mebutate, and topical diclofenac, as well as photodynamic therapy (PDT) performed with 5-aminolevulinic acid (ALA) solution or methyl aminolevulinate (MAL).

Although all of these treatment options have varying degrees of proven efficacy for the clearance of AKs, none of the newer therapies have been tested in head-to-head clinical trials to reveal clinical superiority among them. As such, it is not uncommon that clinicians find themselves at odds as to which therapy to choose from and which modality could achieve the best clearance results in their patients.

International guidelines introduced

This growing sense of urgency has led to the establishment of the first internationally accepted treatment guidelines for actinic keratosis, a work recently put forth by the collaboration between the European Dermatology Forum and the International League of Dermatological Societies (ILDS).

“There has been a growing need for international guidelines regarding the treatment of actinic keratosis, witnessed in the different conceptions of actinic keratosis and treatment implications in the international community. With the introduction of the global AK treatment guidelines, our hope is to bridge the divide and further advance and standardize the perception of AKs and how to best treat and manage these lesions in different clinical scenarios. This includes optimal treatment strategies and recommendations for solitary AK lesions and groups of lesions, as well as field cancerization cases,” says Professor Eggert Stockfleth, M.D., Klinik for Dermatology, Venereology, and Allergy, St. Joseph Hospital, Ruhr University Bochum, Bochum, Germany.

Dr. Stockfleth spearheaded the guidelines subcommittee, an international expert panel consisting of fifteen dermatologists nominated by the ILDS, three dermatopathologists and one patient representative. The expert team performed a systematic assessment of the efficacy and safety of the available treatment options and put together robust evidence-based (S3) guidelines for the treatment and management of AKs.¹

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Next: Criteria and treatment options

Criteria for guidelines

According to Dr. Stockfleth, the global AK guidelines were formulated under very rigorous conditions and were based on the clinical data from over 500 papers that were included in the extensive Cochrane review. The evidence in the papers was critically reviewed for quality, and the level of evidence for each modality was assessed and graded, the results of which were used to help generate different treatment recommendations for specific clinical scenarios, including patients with solitary AK lesions, multiple lesions (<5 AKs/region, and field cancerization), as well as high-risk AK lesions (i.e., high-risk location or occurring in immunosuppressed individuals such as organ transplant recipients).

The clinical data was vetted and therapeutic recommendations were made and based on a 5-point GRADE (Grading of Recommendations Assessment, Development and Evaluation) scale that included the range:

• Strong recommendation for use (“we recommend”)
• Weak recommendation for use (“we suggest”)
• No recommendation (“we cannot make a recommendation with respect to”)
• Weak recommendation against (“we suggest not to”)
• Strong recommendation against (“we recommend not to”)

“These global guidelines for AKs represent the highest level of evidence-based work that has ever been done on the subject of AKs. The goal of the S3 actinic keratosis guidelines program was to develop a deeper insight into what AKs are and to look at the safety and efficacy of the myriad of new drugs that are currently being used to treat actinic keratoses, as well as to provide a heightened global awareness of AKs and the optimal treatment modalities at our disposal,” Dr. Stockfleth says.

Choosing a treatment option

The development of AKs is a clear biologic signal that the patient has received too much cumulative sun exposure over the years. In these cases, not only can AKs arise, but basal cell carcinoma (BCC) and melanoma can develop as well. When presented with AKs, wary physicians will perform a thorough skin exam regularly, depending on the clinical presentation of the patient.

Therapy for actinic keratosis can basically be divided into lesion-directed treatment options (i.e., cryotherapy, electrodessication and curettage, laser surgery), and field-directed treatment options (i.e. imiquimod, ingenol mebutate, 5-FU, diclofenac, and PDT).

According to Dr. Stockfleth, all of the agents currently available are effective, and choosing the most effective agent and treatment regimen can depend on different factors, including:

• Severity/extent of the clinical presentation
• Downtime and tolerability
• Logistics
• Cost

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Disclosures: Dr. Stockfleth reports no relevant disclosures.

Reference:

1. Werner RN, Jacobs A, Rosumeck S, Erdmann R, Sporbeck B, Nast A. Methods and Results Report - Evidence and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis -International League of Dermatological Societies in cooperation with the European Dermatology Forum. J Eur Acad Dermatol Venereol. 2015;29(11):e1-66.