Use of reflectance confocal microscopy to evaluate 5-fluorouracil 0.5%/salicylic acid 10% in the field-directed treatment of subclinical lesions of actinic keratosis: subanalysis of a Phase III, randomized, double-blind, vehicle-controlled trial.

BACKGROUND: Actinic keratosis (AK) is a common skin disorder that can progress to invasive squamous-cell carcinoma. AK can present as clinical (visible) or subclinical (invisible) lesions within areas of chronic sun damage. The importance of treating subclinical AK is gaining support. We present a subanalysis of a previously published Phase III, double-blind, vehicle-controlled study (NCT02289768), to assess 5-fluorouracil (5-FU) 0.5%/salicylic acid 10% treatment of subclinical AK lesions, based on reflectance confocal microscopy (RCM). OBJECTIVE: To determine the efficacy of 5-FU 0.5%/salicylic acid 10% as field-directed treatment for subclinical AK lesions using RCM. METHODS: For inclusion in this subanalysis, patients had to have at least three subclinical AK lesions within a 25 cm2 area of skin. Subclinical AK lesions were diagnosed according to the presence of three key RCM criteria: architectural disarray; keratinocyte atypia and pleomorphism at the basal, spinous and granular layer. Subclinical AK lesions were evaluated by RCM at baseline, after 4, 6 and 12 weeks of 5-FU 0.5%/salicylic acid 10% treatment or vehicle, and 8 weeks following the end of treatment. RESULTS: Twenty-seven patients were included: 17 [mean age = 72.2 years, standard deviation (SD) = 6.3] received 5-FU 0.5%/salicylic acid 10% treatment and 10 (mean age = 76.4 years, SD = 3.9) received vehicle. Eight weeks following the end of treatment, the mean number of subclinical lesions declined (from 3.0 at baseline) to 0.3 (95% confidence interval [CI] 0.06-0.57) for the 5-FU 0.5%/salicylic acid 10% group and 1.6 (95% CI 0.52-2.68) in the vehicle group (reductions of 90% [95% CI 72.1-107.1] vs. 47% [95% CI 24.8-69.5], respectively; P = 0.005). The proportion of patients receiving 5-FU 0.5%/salicylic acid 10% showing complete clearance of three preselected subclinical AK lesions was numerically greater than in the vehicle group (69% vs. 40%, respectively; P = 0.183). CONCLUSION: To the best of our knowledge, this is the first randomized, vehicle-controlled study investigating 5-FU 0.5%/salicylic acid 10% treatment for subclinical AK lesions. The present data suggest some treatment efficacy for subclinical AK lesions detected using RCM. However, this subanalysis was not sufficiently powered and should be reproduced in a larger, subsequent cohort.

Treatment monitoring of 0.5% 5-fluorouracil and 10% salicylic acid in clinical and subclinical actinic keratoses with the combination of optical coherence tomography and reflectance confocal microscopy.

BACKGROUND: Reflectance confocal microscopy (RCM) and high-definition optical coherence tomography (HD-OCT) allow the observation in vivo of dynamic changes in response to non-surgical treatment of actinic keratosis and field of cancerisation. OBJECTIVE: To non-invasively assess the pharmacodynamic changes induced by treatment with low dose 5-fluorouracil and 10% salicylic acid by means of RCM and high-definition OCT in field cancerization and actinic keratosis. METHODS: Twenty patients aged >50 years with diagnosis of actinic keratosis on the head and face and indication for treatment with 0.5% 5-fluorouracil and 10% salicylic acid were enrolled. An area of 25 cm² including visible type I and II AK and subclinical AK was treated once daily during 6 weeks and examination was performed with RCM and HD-OCT before treatment and 2 weeks after the end of treatment RESULTS: High-definition optical coherence tomography results at baseline of mean thickness of the stratum corneum and epidermis were in AK 10.4 (SD = 4.99) and 43.3 (SD = 24.01) µm respectively and in subclinical AK 3.7 (SD = 2.15) and 30.05 (SD = 16.85) µm. At week 8 (2 weeks after the end of treatment) measurements of stratum corneum and epidermis were significantly reduced in AK and subclinical AK for stratum corneum and epidermis. In RCM at week 8 scaling, detached corneocytes, atypical honeycomb, round nucleated cells in the spinosum granulosum layer, round vessels (dermal papillae), inflammatory cells and total AK score were significantly reduced in AK and subclinical AK. CONCLUSIONS: Evaluation of AK and subclinical AK by RCM and HD-OCT showed objective improvement after treatment with 5-fluorouracil and 10% salicylic acid. These methods allowed the study of dynamic changes in the tissue at a subclinical level.