Efficacy and safety of microneedling, fractional CO2 laser, and cryotherapy combined with 5-aminolevulinic acid photodynamic therapy in the treatment of actinic keratosis: A multicenter prospective randomized controlled study

Background: Photodynamic therapy (PDT) for actinic keratosis (AK) is limited by the depth of treatment. Microneedling or fractional CO2 laser can facilitate the penetration of photosensitizer, while cryotherapy can treat deeper tissues but is not suitable for field cancerization. Objective: To investigate the efficacy of microneedling, fractional CO2 laser, and cryotherapy in combination with PDT for AK.Methods: Patients with AK were randomized into 4 groups, including group A with microneedling + PDT, group B with fractional CO2 laser + PDT, group C with cryotherapy + PDT, and group D with PDT. After 12 weeks, the clinical, dermoscopic, and reflectance confocal microscopy (RCM) outcomes were assessed.Results: A total of 129 patients were included in this study, with 31, 30, 35, and 31 patients in each group, yielding clinical response rates of 90.3%, 93.3%, 97.1%, and 74.2%, respectively (P=0.026). The RCM response rates were 71.0%, 80.0%, 85.7%, and 54.8%, respectively (P=0.030). The dermoscopic response rates were 77.4%, 83.3%, 88.6%, and 60.0%, respectively (P=0.039). Group C showed the best efficacy in terms of clinical, dermoscopic, and RCM outcomes. Conclusions: All three treatments improved the efficacy of PDT and were well tolerated, with cryotherapy + PDT showing the best efficacy.