Reflectance Confocal Microscopy for Treatment Response Monitoring in Locally Advanced Basal Cell Carcinoma Treated...

Background/Objectives: Conventional clinical and dermoscopic assessment may overestimate treatment response in locally advanced basal cell carcinoma (laBCC) treated with Hedgehog pathway inhibitors due to treatment-induced fibrosis, pigment retention, and stromal remodeling. Reflectance confocal microscopy (RCM) enables noninvasive, near-histologic resolution skin imaging and may improve response evaluation accuracy. This study evaluated the role of RCM in monitoring treatment response and guiding presurgical planning in laBCC patients treated with sonidegib. Methods: In this prospective, single-center, observational pilot study, 15 consecutive patients with laBCC unsuitable for upfront surgery received sonidegib 200 mg daily. Treatment response was assessed using integrated clinical examination and RCM at baseline and follow-up. Study-specific response categories (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) were adapted from RECIST principles. Presurgical RCM mapping was performed in partial responders. Interobserver agreement between two blinded RCM readers was assessed using Cohen's kappa (κ). Results: The objective response rate was 93.3% (CR: 26.7%; PR: 66.7%; PD: 6.7%). Dose modifications were required in 73.3% of patients; adverse events occurred in 60.0%, most commonly dysgeusia (33.3%) and muscle cramps (20.0%). Clinical-RCM discordance was identified in 13.3% of patients: lesions classified as CR by conventional evaluation were reclassified as PR after RCM detected persistent basaloid tumor nests, prompting treatment continuation (Interobserver agreement: κ = 0.62-0.86). Conclusions: RCM identified residual disease missed by conventional assessment, directly influencing treatment decisions. These findings support integrating RCM into a multimodal, response-adapted management strategy for laBCC. However, the limited sample size warrants cautious interpretation, and larger multicenter studies are required before broad clinical implementation.