Abstract
BACKGROUND: Actinic keratoses (AKs) are precancerous lesions that may progress to squamous cell carcinoma (SCC). Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is an established treatment, often preceded by mechanical curettage to enhance photosensitizer penetration. However, curettage is associated with pain and discomfort, necessitating alternative pretreatment strategies, also applicable in daylight PDT. METHODS: Thirty-six patients with symmetrical facial AKs were randomized to receive MAL-PDT on two contralateral areas: one pretreated with a 10% urea-based keratolytic compound (UBC) for 14 days and the other untreated (control). Protoporphyrin IX (PpIX) fluorescence, clinical outcomes, cosmetic results, and patient satisfaction were assessed. Statistical analyses included the Wilcoxon, Mann-Whitney, and chi-squared tests (p ≤ 0.05). RESULTS: The urea-pretreated group showed significantly higher fluorescence intensity (median: 7 [5-9]) vs. controls (median: 5 [3-6]; **p < 0.0001**), indicating improved MAL penetration. Both groups had significant AK reductions (**p = 0.02**). The reduction in Olsen grade I AKs was greater with UBC (**p < 0.0001**), while no significant differences were observed for grade II lesions. Tolerability and patient satisfaction were high, with no significant differences in pain scores, local skin reactions, or cosmetic outcomes. CONCLUSIONS: Pretreatment with a 10% UBC enhances PpIX fluorescence and improves efficacy in grade I AKs when compared to no pretreatment. Thus, it provides a non-invasive pretreatment option with good efficacy in thin AKs, along with good patient satisfaction and safety.