Background and Aims:
Actinic keratosis (AK) is recognised as a precursor to squamous cell carcinoma (SCC). There are various AK treatments available to lower the risk of SCC transformation and address field pre-cancerisation including lesion-directed therapy such as cryotherapy, curettage and laser ablation, field-directed therapy such as topical gels and photodynamic therapy. However, currently there are no clear recommendations or guidelines as to which modality of treatment is unanimously superior. The purpose of this systematic review is to evaluate the effectiveness of 5-fluorouracil (5FU) in comparison to other treatments in the reduction of actinic keratosis lesions.
Methods:
A systematic search was conducted on the library databases MEDLINE, EMBASE and Cochrane to identify randomised controlled trials (RCTs) that use 5-fluorouracil in the treatment of actinic keratoses in humans. The primary outcome was treatment effectiveness, reported as reduction in the number of actinic keratosis lesions. Secondary outcomes assessed were adverse events, tolerability, cost and adherence.
Results:
After screening, 15 RCTs were included with a total of 1966 patients with actinic keratosis. 5-fluorouracil of different strengths as well as comparison with other treatments such as imiquimod, photodynamic therapy, diclofenac, ingenol mebutate gel was assessed. 5FU is an effective therapy for AKs with 100% clearance rates achieved in up to 75% of patients when used in combination with microneedling and 96% when used as monotherapy after 4 weeks. Overall, 5FU remains a relatively tolerable therapy with expected adverse effects including erythema, inflammation and irritation. Treatment may be limited by duration and adherence to treatment course.
Conclusions and Significance/Impact:
5FU is a safe, accessible and effective therapy for actinic keratoses. Further studies should explore means to enhance treatment efficacy with combination therapies to reduce treatment duration and increase compliance.