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Background: Basal cell carcinomas (BCCs) have previously been treated off‐label with ingenol mebutate (IM). Ablative fractional laser (AFL) may improve efficacy of IM by increasing drug uptake in the tumour. Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) detect BCC non‐invasively. Our aim was to investigate BCC response and tolerability after combined AFL and IM treatment of low‐risk BCCs. Methods: Twenty patients with histologically verified superficial (n = 7) and nodular (n = 13) BCCs were treated with combined fractional CO2‐laser (10 600 nm) and IM 0.015% or 0.05%, the concentration depending on anatomical location. BCC response was evaluated clinically, by OCT and RCM at day 29 and 90 after first treatment, and histologically at day 90. Treatment was repeated at day 29 if BCC persisted. Local skin reactions (LSRs) were assessed using LSR scale at all visits. Results: At day 29, 18/20 patients received a second treatment due to residual BCC detected clinically, by OCT or RCM. OCT and RCM presented subclinical BCCs in five of 20 cases (25%). At day 90, overall histological cure rate was 70%, corresponding to clinical (65%) and OCT/RCM (60%) cure rates, and agreement between evaluation methods was substantial (kappa ≥ 0.796, P < 0.0001). Clearance rates were similar for sBCCs and nBCCs (P = 0.354) and for lesions treated with IM 0.015% and 0.05% (P = 0.141). LSRs were tolerable, but scarring was observed in the majority of cleared patients. Conclusion: Two treatments of combined AFL and IM show potential to treat low‐risk BCCs with acceptable tolerability. OCT and RCM show promise to detect subclinical BCCs at short‐term follow‐up. [ABSTRACT FROM AUTHOR]

Summary: Background: Physical pretreatments can potentiate the efficacy of daylight photodynamic therapy (dPDT), but clinical comparative studies remain limited. Objectives: Performed in large skin areas with actinic keratoses (AKs) and photodamage, this blinded, randomized clinical trial compared the efficacy and safety of dPDT after tailored skin pretreatment using ablative fractional laser (AFL) or microdermabrasion (MD). Methods: Two ≥ 50‐cm2 side‐by‐side skin areas were randomized to receive a single treatment with AFL‐dPDT or MD‐dPDT. Pretreatment parameters were tailored according to AK grade and skin constitution to ensure standardized immediate end points. Subsequently, methyl aminolaevulinate was applied, followed by 2‐h daylight exposure. The primary outcome comprised blinded assessment of AK clearance at the 3‐month follow‐up. Results: In 18 patients with 832 AKs, AFL‐dPDT provided significantly higher AK clearance (81% vs. 60%, P < 0·001), led to fewer new AKs (P < 0·001) and showed superior improvement in dyspigmentation (P = 0·003) and skin texture (P = 0·001) vs. MD‐dPDT. Peaking at days 3–6, AFL‐PDT induced more intensified local skin responses (P = 0·004), including instances of Staphylococcus aureus infection (n = 3). Patients nonetheless preferred AFL‐dPDT (P = 0·077), due to lower pretreatment‐related pain (P = 0·002) and superior cosmesis (P = 0·035) and efficacy compared with MD‐dPDT. Conclusions: AFL‐dPDT is an effective treatment for patients with AK with extensive field cancerization, although AFL pretreatment is associated with intensified local skin reactions. What's already known about this topic? Different physical skin pretreatments have been shown to potentiate the efficacy of daylight photodynamic therapy (dPDT), but comparison studies are lacking. What does this study add? Using tailored pretreatment parameters to obtain standardized immediate end points prior to dPDT, ablative fractional laser provided superior lesional clearance and enhanced rejuvenating effects, but increased local skin reactions compared with pretreatment with microdermabrasion.Ablative fractional laser‐assisted dPDT represents a viable, intensified treatment strategy for patients with multiple actinic keratoses and large areas of photodamaged skin. Linked Editorial:Wolf. Br J Dermatol 2019; 180:697–698. Respond to this article [ABSTRACT FROM AUTHOR]