Simulated daylight versus conventional PDT for mild to moderate actinic keratoses: A randomized controlled trial

BACKGROUND: Conventional photodynamic therapy (C-PDT) with red light is an effective but painful treatment for patients with actinic keratoses (AKs). Simulated daylight PDT (SDL-PDT) is most likely less painful, but its effectiveness has not been thoroughly investigated. OBJECTIVES: To evaluate if SDL-PDT is non-inferior to C-PDT in terms of effectiveness in the treatment of mild to moderate AKs. Additionally, pain perception, local skin reactions and patient preferences were assessed. METHODS: This single-centre, non-inferiority (-8% margin), randomized controlled trial included adults with symmetrically distributed mild to moderate AKs across one or more anatomical sites. These sites were randomly assigned to treatment with a single session of C-PDT on one half of the affected area and SDL-PDT on the other half, using 5-aminolevulinic acid hydrochloride as the prodrug. Pain during illumination was assessed using a 0-10 numeric rating scale (NRS). Patient preferences were recorded through self-report forms. Follow-up assessments were conducted at 3 months to evaluate early treatment failure and at 1 year to determine overall clearance rates. RESULTS: In total, 69 participants with 1458 mild to moderate AKs were treated. Most lesions (89.9%) were located on the face and scalp and were diagnosed through clinical and dermoscopic evaluation. After 1 year, the clearance rate was 71.0% for SDL-PDT and 85.3% for C-PDT (p < 0.001), thus failing to demonstrate non-inferiority. Illumination was reported to be more painful during C-PDT (mean NRS score of 6.6) compared with SDL-PDT (mean NRS score of 0.8) (p < 0.001). One day after treatment, 98.3% of respondents expressed a preference for SDL-PDT. CONCLUSION: SDL-PDT showed lower clearance rates than C-PDT but caused significantly less pain. Although not supported as a primary treatment for AKs, SDL-PDT may be considered for patients prioritizing treatment tolerability within shared decision-making. This randomized controlled trial was registered at http://www.researchweb.org/ (Project ID: 264721).