Original Research

CO2 Laser Ablative Fractional Resurfacing Photodynamic Therapy for Actinic Keratosis and Nonmelanoma Skin Cancer: A Randomized Split-Side Study

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Follow-up was conducted at 1 week, 1 month, 3 months, and 6 months after the PDT procedure. The primary end points were clinical clearance of NMSC lesions at 1, 3, and 6 months posttreatment and histological clearance at 6 months. Secondary end points assessed quality of life and functional improvements.


Twenty-four potential participants experiencing AKs and/or NMSCs were screened for the study, with 19 meeting inclusion criteria. All participants were white, non-Hispanic, and had Fitzpatrick skin types I or II. Treated areas for all participants had field cancerization defined as at least 1 AK per square centimeter. All 19 participants enrolled in the study completed the posttreatment evaluations up to 6 months. All AFR-pretreated sites showed superior results in reduction in number, size, or hyperkeratosis of AKs at all follow-up visits, with a complete absence of new AK formation at the 6-month follow-up (Table). Conversely, sites treated with standard PDT only showed some recurrence of AKs at 6 months. Of the 3 participants who had biopsy-confirmed BCCs on the AFR-pretreated side, there were 3 persistent lesions after treatment at the 6-month visit. Two participants experienced persistence of a confirmed SCC in situ that was on the laser-pretreated side only (1 on the forehead and 1 on the hand), whereas 1 participant with an SCC on the leg at baseline had no recurrence at 6 months. A participant who received treatment on the lower lip had persistence of actinic cheilitis on both the AFR- and non–AFR-treated sides of the lip.

Scalp and facial sites healed fully in an average of 7 days, whereas upper extremities—forearm and hands—took approximately 14 days to heal completely. Lower extremity AFR-pretreated sites exhibited substantial weeping, resulting in prolonged healing of approximately 21 days for resolution of all scabbing. Pain during treatment was mild to moderate, as field blocks with local anesthesia and topical anesthetic were used prior to AFR treatment. No novel adverse events were reported in the combined use of laser AFR and PDT; all adverse events noted have been recorded in studies of the separate techniques.16,17


In this split-sided study in patients with field cancerization, the use of CO2 laser AFR before treatment with PDT increased AK lesion clearance compared to ALA-PDT alone. Prior studies of fractional laser–assisted drug delivery on porcine skin using topical MAL showed that laser channels approximately 3-mm apart were able to distribute protoporphyrin through the entire skin.6 The ablative nature of AFR theoretically provides deeper and more effusive penetration of the ALA solution than using conventional PDT or erbium:YAG lasers with PDT.7,8 Helsing et al11 applied CO2 laser AFR MAL-PDT to AKs in organ transplant recipients and obtained complete responses in 73% of patients compared to a complete response of 31% for AFR alone. The results reported in our study are consistent with Helsing et al,11 showing a complete clinical response for 14 of 19 patients (74%), of whom 4 (21%) had no recurrence of NMSC and 10 (53%) had no recurrence of AK on the AFR-PDT–treated side.

The pretreatment process required for the laser AFR added time to the initial visit compared to conventional PDT, which is balanced by a reduced PDT incubation time (1 hour vs the approved indication of 14–18 hours for face/scalp or 3 hours for upper extremities under occlusion). The use of microneedling as an alternative pretreatment procedure before PDT also has been investigated, with the aim of decreasing the optimum ALA absorption time. The mean reduction in AKs (89.3%) was significantly greater than for PDT alone (69.5%; P<.05) in a small study by Spencer and Freeman.18 Although microneedling is less time-intensive and labor-intensive than laser AFR, the photocoagulative effect and subsequent microhemorrhages resulting from AFR should result in much deeper penetration of ALA solution than for microneedling.

The limitations of this proof-of-concept study arose from the small sample size of 19 participants and the short follow-up period of 6 months. Furthermore, the unblinded nature of the study could create selection, detection, or reporting bias. Further follow-up appointments would aid in determining the longevity of results, which may encourage future use of this technique, despite the time-consuming preparation. A larger study with follow-up greater than 1 year would be beneficial, particularly for monitoring remission from SCCs and BCCs.


Pretreatment with CO2 laser AFR before ALA-PDT provided superior clearance of AKs and thin NMSCs at 6 months compared to ALA-PDT alone (Figure). Additionally, the incubation period for ALA absorption can be reduced before PDT, leading to a shorter treatment time overall. The benefits of AFR pretreatment on AK clearance demonstrated in this study warrant further investigation in a larger trial with a longer follow-up period to monitor maintenance of response.

A, A patient with actinic keratosis who was randomized to receive laser ablative fractional resurfacing pretreatment on the right side of the forehead. B, At 6 months posttreatment, skin was smoother and more elastic with decreased lentiginosis and more A B uniform color.

The authors thank the patients who participated in this study. Editorial assistance was provided by Louise Gildea, PhD, of JK Associates Inc, part of the Fishawack Group of Companies (Fishawack, United Kingdom), funded by Sun Pharmaceutical Industries, Inc.


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