Efficacy of different photoprotection strategies in preventing actinic keratosis new lesions after photodynamic therapy. The ATHENA study: a two-center, randomized, prospective, assessor-blinded pragmatic trial

Abstract

Background: Treatment of actinic keratosis (AK) and field cancerization with photodynamic therapy (PDT) is an effective therapeutic approach with a significant reduction in the number of AK lesions (–75% or more) associated with a significant cosmetic improvement of the photodamaged skin. Recently, also, the daylight PDT (DL-PDT) has proven to be as effective as the conventional PDT (C-PDT), but with a better tolerability. After C-PDT and DL-PDT it is advised to use photoprotection strategies to improve the clinical evolution and prevent the appearance of new AK lesions that usually appear 3–6 months after the last phototherapy session. However, there are no robust clinical data regarding the type of photoprotection to be used (SPF level, duration of treatment, etc.) after successful PDT.

Study aim: The present study (ATHENA trial) evaluated the efficacy and tolerability of a topical product based on 0.8% piroxicam and 50+ solar filters (ACTX), applied twice a day as sequential therapy after C-PDT or DL-PDT on the evolution of AK lesions number compared to the use of very high photoprotection products commonly used in this clinical setting (SPF50+ or SPF100+ associated with photolyase) (Standard Sunscreens: SS group). Subjects and methods: This was a multicenter, randomized, two-arm, prospective controlled, assessor-masked outcome evaluation, parallel group (1:1), pragmatic study of 6 months duration in patients with multiple AK lesions suitable for photodynamic therapy. The objectives of the study were the evaluation of the evolution of the number of AK lesions during the period of treatment/application of the study products, and the Investigator global clinical assessment score (IGA score; 4: marked improvement, 3: good, 2: moderate; 1 no improvement; 0: worsening) 2, 3, and 6 months after the last PDT session. A total of 68 subjects (50 men, 18 women; mean age 70 years), 34 assigned to treatment with ACTX and 34 to treatment with SS (17 treated with a SPF50+ and 17 with a photolyase-containing SPF100+ products), were enrolled in the study.

Results: The number of AK lesions present before C-PDT/DL-PDT was 11.8 ± 5.8 in the ACTX group and 12.4 ± 6.9 in the SS group. In both groups, there was a progressive reduction of AK lesions observed at baseline (–86% and –87% after 2 months and –88% and –83% at month 3 in ACTX and in the SS group, respectively). At month 6, AK mean lesion number was 1.8 ± 1.6 in the ACTX and 3.2 ± 2.3 in the SS group; this difference was statistically significant (p = 0.03). The IGA score at the end of the study was 3.2 in the ACTX and 2.7 in the SS group (p = 0.05). The percentage of subjects with an IGA score of 4/3 (very good or good) was 81% in the ACTX and 55% in the SS group (p = 0.06).

Conclusion: In subjects with AK treated with C-PDT or DL-PDT, a “medicalized” photoprotection treatment is associated with a favorable clinical outcome with progressive reduction of lesions. In contrast to a very high photoprotection (SPF50+ or SPF100+/photolyase), the use of piroxicam 0.8%/SPF 50+ is associated with a significantly greater improvement in clinical evolution of AK lesions.

Keywords:

• Actinic keratosis
• Photodynamic therapy
• Piroxicam
• Cancerization field

Acknowledgments

Trial number: ISRCTN16168548.