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Background: Actinic keratosis (AK) is a common premalignant skin condition that might have the ability to progress into squamous cell carcinoma. Due to the high incidence of AK, treatment of this disease significantly impacts healthcare spending., Objectives: To determine which commonly prescribed field-directed treatment is the most cost-effective, when comparing 5-fluorouracil (5-FU) 5%, imiquimod (IMQ) 5%, ingenol mebutate (IM) 0·015% and methyl aminolaevulinate photodynamic therapy (MAL-PDT) for AK in the head and neck region., Methods: We performed an economic evaluation from a healthcare perspective. Data were collected alongside a single-blinded, prospective, multicentre randomized controlled trial with 624 participants in the Netherlands. The outcome measure was expressed as the incremental cost-effectiveness ratio, which is the incremental costs per additional patient with ≥ 75% lesion reduction compared with baseline. This trial was registered at ClinicalTrials.gov, number NCT02281682., Results: The trial showed that 5-FU was the most effective field treatment for AK in the head and neck region. Twelve months post-treatment, the total mean costs for 5-FU were significantly lower (€433) than the €728, €775 and €1621 for IMQ, IM and MAL-PDT, respectively. The results showed that 5-FU was a dominant cost-effective treatment (more effective and less expensive) compared with the other treatments, 12 months post-treatment., Conclusions: Based on these results, we consider 5-FU 5% cream as the first-choice treatment option for multiple AKs in the head and neck area. What's already known about this topic? Due to the increasing incidence of actinic keratosis (AK), the recommended treatment results in a considerable socioeconomic burden for (dermatological) healthcare. Although cost-effectiveness modelling studies have been performed in which different treatments for AK were compared, a prospective clinical trial comparing four frequently prescribed treatments on effectiveness and resource consumption within a time horizon of 12 months has never been conducted. What does this study add? This is the first study examining the cost-effectiveness of 5-fluorouracil 5% cream, imiquimod 5% cream, ingenol mebutate 0·015% gel and methyl aminolaevulinate photodynamic therapy, with data collected in a randomized controlled trial over a time horizon of 12 months. We found that 5-fluorouracil was a dominant cost-effective treatment (more effective and less costly), based on data from the Netherlands. Linked Comment: Steeb et al. Br J Dermatol 2020; 183:612., (© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Basal cell naevus syndrome (BCNS) is associated with germline mutations in the PTCH1 gene. Postzygotic mosaicism can also cause BCNS. Here we describe two patients, one with multiple basal cell carcinomas (BCCs) and one with clinical BCNS, who had no PTCH1 mutation in DNA extracted from blood. In both patients, we performed genetic analysis on different BCCs, revealing the presence of a shared PTCH1 mutation in all tumours. Our findings show that in patients with symptoms of BCNS and initial absence of a PTCH1 mutation in blood, genetic profiling of BCCs can detect postzygotic mosaicism. What's already known about this topic? Basal cell naevus syndrome (BCNS) is associated with germline mutations in the PTCH1 gene, but it can also be caused by low-grade postzygotic mosaicism in PTCH1. What does this study add? In patients suspected of having BCNS or patients with multiple basal cell carcinomas (BCCs) with a special distribution on the body and no mutation detected in blood, it is worthwhile to search for a shared PTCH1 mutation in their BCCs as this can detect postzygotic mosaicism. This information is important to ensure proper surveillance programmes, choose the right therapy and provide adequate genetic counselling., (© 2018 British Association of Dermatologists.)

Background: Basal cell carcinoma (BCC) is the most common type of skin cancer and incidence rates are increasing. Photodynamic therapy (PDT) is a frequently used treatment, especially for superficial BCC (sBCC). Two topical photosensitizing agents are currently used to treat sBCC, namely 5-aminolaevulinic acid (ALA) and its ester, methyl aminolaevulinate (MAL). Previous research showed a high efficacy for ALA-PDT using a twofold fractionated illumination scheme in which two light fractions of 20 J cm -2 and 80 J cm -2 were delivered 4 h and 6 h after ALA application., Objectives: To evaluate whether twofold ALA-PDT is superior to conventional MAL-PDT for sBCC., Methods: We performed a single-blind, randomized, multicentre trial in the Netherlands., Results: Overall, 162 patients were randomized either to conventional MAL-PDT or twofold ALA-PDT. After 12 months, a total of six treatment failures occurred following ALA-PDT and 13 treatment failures occurred following MAL-PDT. The 12-month cumulative probability of remaining free from treatment failure was 92·3% [95% confidence interval (CI) (83·7-96·5)] for ALA-PDT and 83·4% (95% CI 73·1-90·0) for MAL-PDT (P = 0·091)., Conclusions: The twofold ALA-PDT scheme resulted in fewer recurrences, although the difference between both treatment groups was not statistically significant. However, ALA-PDT resulted in higher pain scores and more post-treatment side-effects compared with MAL-PDT., (© 2017 British Association of Dermatologists.)

Background: A recent noninferiority randomized controlled trial (RCT) indicated that imiquimod can be considered as superior to methylaminolevulinate photodynamic therapy (MAL-PDT) in the treatment of superficial basal cell carcinoma (sBCC). Knowledge of treatment effectiveness in subgroups of patients is of great value in clinical practice to select the most effective treatment for an individual patient with sBCC., Objectives: To explore whether the relative treatment effect of MAL-PDT and imiquimod is consistent across subgroups defined by patient and tumour characteristics., Methods: Data were derived from a single-blinded, noninferiority, multicentre RCT comparing MAL-PDT, topical imiquimod and fluorouracil (ISRCTN79701845). Treatment success was defined as free of tumour recurrence at 12-month follow-up. Subgroup analyses were performed for subgroups defined by sex, age, tumour location and tumour size., Results: Two hundred and two patients received MAL-PDT and 198 received imiquimod. The superiority of imiquimod vs. MAL-PDT was observed in subgroups of females, sBCC on the trunk and large tumours with risk differences in favour of imiquimod of 18·4% [95% confidence interval (CI) 7·8-29·0%], 21·0% (95% CI 10·9-31·1%) and 18·9% (95% CI 7·1-30·7%), respectively. Higher probability of treatment success for imiquimod vs. MAL-PDT was consistently found in all other subgroups with the exception of sBCC localized on the lower extremities in older patients. In the latter subgroup, the risk difference at the expense of imiquimod was -57·3% (95% CI -81·7% to -32·9%)., Conclusions: Imiquimod remains the first-choice treatment for sBCC in terms of effectiveness. In older patients with sBCC on the lower extremities MAL-PDT might be preferred. Results should be interpreted carefully as subgroup analyses were exploratory and not driven by prior hypotheses., (© 2014 British Association of Dermatologists.)

Background: A recent noninferiority randomized trial showed that in terms of clinical effectiveness imiquimod was superior and topical fluorouracil noninferior to methylaminolaevulinate photodynamic therapy (MAL-PDT) for treatment of superficial basal-cell carcinoma (sBCC). Although it was expected that MAL-PDT would be more costly than either cream, a full cost-effectiveness analysis is necessary to determine the balance between effectiveness and costs., Objective: To determine whether imiquimod or topical fluorouracil are cost-effective treatments for sBCC compared with MAL-PDT., Methods: An economic evaluation was performed from a healthcare perspective. Data on resource use and costs were collected alongside the randomized clinical trial. The incremental cost-effectiveness ratio was expressed as the incremental costs per additional patient free of tumour recurrence., Results: At 12 months follow-up, the total mean costs for MAL-PDT were €680, for imiquimod cream €526 and for topical fluorouracil cream €388. Both imiquimod and topical fluorouracil were cost-effective treatments compared with MAL-PDT. Comparing costs and effectiveness of both creams led to a incremental investment of €4451 to achieve an additional patient free of tumour recurrence. The acceptability curve showed that, for a threshold value of €4451, the probability of imiquimod being more cost-effective than topical fluorouracil was 50%., Conclusion: Based on the 12 months follow-up results, imiquimod and topical fluorouracil cream are more cost-effective than MAL-PDT for treatment of sBCC. Hence, substituting MAL-PDT with either imiquimod or topical fluorouracil results in cost savings; these savings will be larger for topical fluorouracil. Long-term follow-up effectiveness data are necessary to confirm the cost-effectiveness of imiquimod vs. topical 5-fluorouracil cream., (© 2014 British Association of Dermatologists.)

Background: Skin cancer incidence rates have been increasing for decades and this increase is expected to continue. Surgical excision (SE) is the treatment of first choice for nodular basal cell carcinoma (nBCC). Photodynamic therapy (PDT) has proven to be an effective treatment for superficial basal cell carcinoma. Its long-term efficacy in nBCC has not yet been established., Objectives: Prospectively compare the efficacy of 5-aminolaevulinic acid (ALA)-PDT and SE in terms of failure rates with long-term follow-up. Determinants of failure in the study population, such as the effect of tumour depth, were analysed retrospectively., Methods: A randomized controlled trial in 173 primary nBCCs in 149 patients. Primary nBCCs were randomly assigned either to PDT (n = 85) or to SE (n = 88). Tumours treated with PDT were illuminated twice on the same day, 4 h after application of ALA cream, 3 weeks after debulking. SE was performed under local anaesthesia with a 3-mm margin, followed by histological examination. An intention-to-treat analysis was performed., Results: In total, 171 primary nBCCs in 149 patients were treated. A 3-year interim analysis revealed that the cumulative incidence of failure was 2.3% for SE and 30.3% for PDT (P < 0.001). Tumour depth and other analysed determinants of failure were not significantly related to treatment failure., Conclusions: SE proved to be significantly more effective than treatment with fractionated illumination ALA-PDT. Therefore, in the treatment of primary nBCC, SE is preferred over PDT following this treatment regimen.