Comparative efficacy of photodynamic therapy versus conventional therapies for actinic keratosis: A systematic review and meta-analysis

BACKGROUND: Photodynamic therapy (PDT) is widely used for actinic keratosis (AK), but its comparative effectiveness versus conventional therapies remains unclear. OBJECTIVE: To systematically evaluate PDT efficacy compared with cryotherapy, 5-fluorouracil, and imiquimod for AK treatment through meta-analysis. METHODS: We conducted a systematic review and meta-analysis, searching PubMed, Embase, Cochrane, and Web of Science databases through June 2025 for randomized controlled trials comparing PDT with active treatments. Primary outcome was complete clearance rate. Risk ratios (RR) with 95 % confidence intervals (CI) were calculated using random-effects models. RESULTS: Thirteen studies (n = 1841) were included. 5-Fluorouracil demonstrated superior efficacy versus PDT at 12 months (74.7 % vs 37.7 %; RR 0.50, 95 % CI 0.40-0.64, P < 0.001). PDT showed comparable efficacy to cryotherapy overall (63.5 % vs 52.4 %, P = 0.154) but was superior for Grade III lesions (56.9 % vs 13.4 %, P = 0.021). Against imiquimod, results varied by population: imiquimod was more effective in immunocompetent patients (53.9 % vs 37.7 %, P = 0.006), while PDT was superior in organ transplant recipients (78 % vs 61 %, P < 0.001). Combination 5-FU pretreatment enhanced PDT efficacy (87 % vs 74 %, P < 0.0001). PDT achieved better cosmetic outcomes than cryotherapy (hypopigmentation: 0-3 % vs 31 %, P < 0.001) and higher patient satisfaction than imiquimod (90 % vs 61 %, P < 0.003). CONCLUSIONS: While 5-fluorouracil monotherapy shows superior efficacy, PDT offers advantages for specific populations and Grade III lesions. Combination approaches optimize outcomes while maintaining PDT's favorable cosmetic and tolerability profile.