While 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is considered a first-line treatment for non-hyperkeratotic actinic keratosis (AK), its effectiveness for Olsen grade (OG) 3 AK lesions has been debated.

This study shows ALA-PDT is an effective and safe treatment for OG 3 AK, achieving high initial (87.88 %) and sustained (89.66 %) complete clearance rates at 3 and 12 months, respectively, comparable to those observed in OG 1/2 AK (p > 0.05).

These findings support ALA-PDT as a favorable non-invasive treatment option for the patients with OG 3 AK.

Actinic keratosis (AK) is a common cutaneous keratinocyte dysplasia categorized by the 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.

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.

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).

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.

Actinic keratosis

Olsen grade

5-Aminolevulinic acid

Photodynamic therapy

© 2025 The Authors. Published by Elsevier B.V.