Photodynamic Therapy vs. 5-Fluorouracil for Field-Directed Treatment of Actinic Keratosis: A Comparative Literature Review

BACKGROUND: Actinic keratosis (AK) is a common precancerous skin condition arising from chronic UV exposure and often involves field cancerization, where visible lesions coexist with subclinical damage. Effective field-directed treatments are critical for preventing progression to squamous cell carcinoma. HYPOTHESIS: Photodynamic Therapy (PDT) may offer superior efficacy, cosmetic outcomes, and patient adherence compared to topical 5-Fluorouracil (5-FU), despite its higher cost and clinical setting requirement. METHODS: This literature review analyzed peer-reviewed studies from 2015–2025 comparing PDT and 5-FU for field-directed AK treatment. Outcomes assessed included lesion clearance, recurrence, tolerability, adherence, cost, and patient satisfaction. RESULTS: PDT demonstrated high clearance rates (70–90%) and excellent cosmetic results, especially in sensitive or extensive areas. Its major advantages include single-session administration and clinical supervision, which support adherence but are offset by higher costs and pain during treatment. In contrast, 5-FU is an affordable, self-applied topical therapy with good efficacy (60–80%) but requires strict adherence over 2–4 weeks. Side effects such as inflammation, erythema, and crusting often reduce compliance. Emerging studies indicate that pre-treatment with 5-FU may enhance PDT efficacy by increasing protoporphyrin IX accumulation, supporting combination or sequential therapy approaches. CONCLUSIONS: Both PDT and 5-FU are viable treatments for AK in field cancerization. PDT offers improved long-term outcomes and cosmetic benefits, while 5-FU remains a cost-effective choice. Treatment should be personalized based on lesion extent, patient lifestyle, tolerance, and resource availability.