Updated Evidence-Based Management Guidelines for Actinic Keratosis

Actinic keratosis
Actinic keratosis – a precursor to squamous cell carcinoma or skin cancer on a man’s hand
A guideline on optimal actinic keratosis (AK) treatment based on the latest evidence for general AK management and for specific patient subgroups is provided.

Characterized by intraepithelial keratinocyte dysplasia and molecular alterations shared with normal chronically sun-damaged skin and squamous cell carcinoma (SCC), actinic keratosis (AK) can progress to malignant SCC and is therefore routinely treated. Yet substantial variation existsin treatment for AK, and recent evidence has highlighted treatments that are most effective.

A randomized, single-blind, controlled trial in 624 patients with 5 or more AKs found that topical 5% 5-fluorouracil (5-FU) was significantly more effective in reducing AK counts at 1 year than 5% imiquimod cream, methyl aminolevulinate photodynamic therapy, or 0.015%-ingenol mebutate gel.

These guidelines on optimal AK treatment were published in the Journal of Dermatological Treatment after study authors reviewed the latest evidence for general AK management and for specific patient subgroups as well.

Patients with solitary/few AKs, absence of field cancerization or in-field SCC, and no immunosuppression:

  • Destructive spot therapies (cryotherapy, etc.)
  • Observation if AKs are asymptomatic and nonhypertrophic
    • Discuss the pros and cons of this approach with the patient
    • Counsel patient on “red flag” signs and symptoms (bleeding, rapid growth, pain) if the patient opts for this approach

Patients with numerous AKs and/or evidence of field cancerization or any AKs with history of invasive in-field SCC, without immunosuppression

  • Destructive spot therapies
  • Offer field therapies; 5-FU is the most effective choice for AK
    • Counsel the patient on the relative benefits, risks, adverse events, and time/cost considerations of the patient’s chosen field therapy, including:
      • A single course of 5-FU provides a nearly 3-fold reduction in AKs at 6 months compared with no treatment, and requires fewer destructive spot treatments
      • At 1 year, 5-FU was found to lead to a 75% relative risk reduction for in-field SCC compared with no treatment, but the absolute risk reduction is 3% meaning only 1 out of every 33 patients will derive benefit in SCC prevention
      • Potential benefits of 5-FU therapy diminish 1 year after treatment and it may need to be regularly repeated

Patients with any AKs or evidence of field cancerization, with chronic immunosuppression or high-risk germline mutation

  • ·Aggressive, universal treatment of AK and/or evidence of field cancerization
    • Destructive spot therapies for hypertrophic AKs
    • 5-FU field-therapy as first-line treatment for AK reduction and SCC prevention, repeated at least annually in areas at high risk for SCC
    • Discuss personal preference and quality of life issues with the patient. Evidence is lacking on this treatment approach, but its benefit-to-harm ratio and cost-effectiveness are projected to be favorable in this patient population

Universal recommendations for all patients with AKs

  • ·   Counsel on primary and secondary skin cancer prevention strategies
    • Emphasize the benefits of regular sunscreen use for AK treatment and prevention and SCC prevention


Navarrete-Dechent C, Marghoob AA, Marchetti MA. Contemporary management of actinic keratosis. J Dermatolog Treat. 2021;32(5):572-574. doi:10.1080/09546634.2019.1682504