Resumen

Objectives: To compare the long-term durability of response of high-density CO₂ laser with low-density CO₂ laser, topical 5-fluorouracil (Efudex), and photodynamic therapy (Metvix) in patients with actinic keratosis using complementary absolute and normalized outcome measures. Introduction: Actinic keratosis (AK) represents a manifestation of ultraviolet (UV)-induced field cancerization, arising within clonally altered keratinocyte populations. While field-directed therapies such as topical 5-fluorouracil, photodynamic therapy, and fractional laser resurfacing (FLR) achieve meaningful short-term clearance, long-term durability remains limited. High-density CO₂ laser resurfacing may provide more sustained field correction through deeper ablation and dermal remodeling. Materials / method: We conducted a retrospective longitudinal analysis of real-world data from patients treated with high- or low-density CO₂ laser, topical 5-fluorouracil, or photodynamic therapy. Treatment episodes were analyzed independently. Outcomes at 6 and 30 months included absolute lesion burden and responder status based on proportional reduction from baseline. Responder proportions were summarized descriptively with exact confidence intervals and prespecified pairwise comparisons. Between-modality differences used rank-based testing with effect sizes estimated by Cliff’s delta. Results: At 6 months, all modalities produced clinically meaningful reductions in AK burden, with no statistically significant differences in responder rates after adjustment. By 30 months, high-density CO₂ laser demonstrated superior durability. Compared with low-density CO₂ laser, topical 5-fluorouracil, and photodynamic therapy, high-density CO₂ laser achieved larger absolute lesion reductions and higher proportions of ≥40% and ≥75% responders (all adjusted p < 0.05). Superiority over low-density CO₂ laser and 5-fluorouracil persisted at the ≥90% responder threshold. Conclusion: High-power and density CO₂ laser provides superior long-term durability of response in the treatment of actinic keratosis compared with low-density CO₂ laser, topical 5-fluorouracil, and photodynamic therapy. The delayed emergence of treatment separation suggests that the benefit of high-density CO₂ laser lies in durable field modification rather than enhanced short-term clearance, consistent with its depth-dependent biological effects on field cancerization.