Duration of sonidegib treatment and its relationship with recurrence after complete response: a multicenter retrospective study

Line-field confocal optical coherence tomography (LC-OCT) is a new non-invasive imaging tool that has demonstrated its usefulness in the diagnosis and monitoring of AKs.The aim of the study was to evaluate by LC-OCT and histopathology if lesions arising during treatment with 4% 5-fluorouracil (5-FU) cream on apparent healthy skin surrounding visible AKs, represent subclinical, unmasked AKs.Methods: Eight adult, immunocompetent patients (all males; phototype II-III; mean age: 69 years) with 5, scattered AKs (grade I or II according to Olsen) comprised in an area of 100 cm2 on the face or scalp were enrolled in an open, multicenter study.Patients were instructed to apply 4% 5-FU cream once a day for 4 weeks on the entire 100 cm2 area containing the visible AKs and the surrounding apparent healthy skin.Patients were clinically evaluated at baseline (T0) after 2 weeks (T1), at the end of treatment (T2) and 1 month after the end of treatment (T3).At T1 and T2, in case of evidence of "subclinical AK" arising on previous healthy skin, LC-OCT was performed in each patient, along with a biopsy of a target lesion for histopathological examination.Results: All patients completed the 8-week study.At T0, the mean number of AKs was 4.4 (range: 3-5).After 2 and 4 weeks of treatment, new, previously undetected lesions became clinically visible in 7 and 8 patients, respectively.At LC-OCT examination, these lesions showed signs of AK.Histopathological examination of the target lesions confirmed the diagnosis of AK.With the detection of subclinical lesions, the mean number of AKs during treatment increased to 8.4 (range: 5-15) at T2 and 10.1 (range: 6-17) at T4, respectively.One month after the end of the treatment (T3), the mean number of AKs decreased to 1.4 (range: 0.3). Conclusions:The results of our study, obtained by LC-OCT and histopathological examination, confirm that the lesions arising on apparently healthy skin around visible AKs during treatment with 4% 5-FU represent true, unmasked, previously subclinical AKs, and not simply inflammatory reactions.Our results also suggest that field-directed treatment should be preferred to lesion-directed ones being able to treat both clinical and subclinical AKs.