The use of ablative laser-assisted photodynamic therapy (PDT) has demonstrated a higher likelihood of lesion clearance among patients with actinic keratosis (AK) compared with the use of PDT alone, with no significant difference in level of pain, according to the results of a systematic review and meta-analysis of relevant randomized controlled trials (RCTs). Findings from the analysis were published in the Journal of the American Academy of Dermatology.

The investigators sought to summarize the current evidence on the safety and efficacy of laser-assisted PDT. Patients with a clinical and/or histopathologic diagnosis of AK were included in the review. The patients evaluated were treated with a combination of PDT and laser. Both 5-aminolevulinic acid and its ester methyl aminolevulinate were permitted to be used as photosensitizers. Ablative and nonablative laser devices were both eligible for use. The researchers included only those RCTs in which the study participants (ie, inter-individual trials) or entire body parts (ie, intra-individual trials) were analyzed. Retrospective studies, observational studies, pseudorandomized trials, crossover studies, and case series were excluded from the analysis.

The primary outcomes were lesion-specific complete clearance rates and local adverse events, which were determined by the number of patients or treated areas that experienced skin irritation. Secondary outcomes included cosmetic outcome (quantified as the number of patients or treatment areas with skin dyspigmentation), patient satisfaction (rated globally as “satisfied” or “very satisfied”), and pain that results from treatment (reported on a visual analogue scale from 0 [none] to 10 [extreme pain]). All outcomes had to be reported ≥2 months and ≤6 months after the conclusion of treatment.

The literature identified 817 references, with 7 RCTs (n=240 patients) selected for meeting all eligibility criteria. Of the 7 studies chosen, 6 assessed methyl-aminolevulinate and 1 evaluated 5-aminolevulinic acid as a photosensitizer. Moreover, 3 of the studies investigated one type of laser device, and the remaining 4 studies examined a different type of laser device.

The use of laser-assisted PDT demonstrated significantly higher clearance rates compared with the use of PDT monotherapy (risk ratio, 1.33; 95% CI, 1.24-1.42; I2 =25%; P <.01). A sensitivity analysis with inter-individual trials only demonstrated a similar effect (risk ratio, 1.41; 95% CI, 1.27-1.56; I2 =0%). 

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None of the studies reported the occurrence of severe adverse events or mentioned situations in which patients had to discontinue therapy. The occurrence of dyspigmentation was reported inconsistently.

The investigators concluded that ablative laser-assisted PDT should be offered upfront in patients with difficult-to-treat AKs, such as hyperkeratotic lesions, acral lesions, or AK in organ transplant recipients.

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Steeb T, Schlager JG, Kohl C, Ruzicka T, Heppt MV, Berking C. Laser-assisted photodynamic therapy for actinic keratosis: a systematic review and meta-analysis [published online September 26, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.09.021