BACKGROUND: Actinic keratosis (AK) is a common cutaneous keratinocyte dysplasia categorized by Olsen Grade (OG) 1-3. OG 3 AK, which has a higher risk of progressing to cutaneous squamous cell carcinoma (cSCC), presents treatment challenges. While 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is effective for non-hyperkeratotic AK (OG 1-2), its efficacy for OG 3 AK remains debated. METHODS: To evaluate the efficacy and safety of ALA-PDT for the treatment of OG 3 AK, this single-center prospective cohort study included 127 patients with histopathologically confirmed AK, grouped by the Olsen grading (OG 3, n=33
OG 1 or 2, n=94). All patients received four sessions of ALA-PDT and were followed up for 12 months. The primary outcome was initial complete clearance (CC) at 3 months, while sustained CC at 12 months was the secondary outcome. Safety was assessed throughout the study. RESULTS: The initial CC rates were 87.88% (29/33) for the OG 3 group and 92.55% (87/94) for the OG 1/2 group. The sustained CC rates at 12 months were 89.66% (26/29) and 86.21% (75/87) for the OG 3 and OG 1/2 groups, respectively. No significant difference was observed between the two groups for either initial CC or sustained CC rates (p>
0.05). Adverse events were mostly mild and transient, though long-lasting erythema at 12 months was more common in the OG 3 group compared with the OG 1/2 group (23.08% vs. 5.33%, p=0.01). CONCLUSION: ALA-PDT demonstrates favorable efficacy and safety profile for OG 3 AK, supporting ALA-PDT as a valuable non-invasive treatment option for OG 3 AK.