No abstract

published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal.If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the "Taverne" license above, please follow below link for the End User

For the treatment of superficial basal cell carcinoma, a prospective, noninferiority, randomized controlled multicenter trial with 601 patients showed that 5% imiquimod cream was superior and 5-fluorouracil cream not inferior to methyl aminolevulinate photodynamic therapy (MAL-PDT) at 1 and 3 years after treatment. No definite conclusion could be drawn regarding the superiority of imiquimod over 5-fluorouracil. We now present the 5-year follow-up results according to the intention-to-treat analysis. Five years after treatment, the probability of tumor-free survival was 62.7% for methyl aminolevulinate photodynamic therapy (95% confidence interval [CI] = 55.3-69.2), 80.5% for imiquimod (95% CI = 74.0-85.6), and 70.0% for 5-fluorouracil (95% CI = 62.9-76.0). The hazard ratio for treatment failure of imiquimod and 5-fluorouracil were 0.48 (95% CI = 0.32-0.71, P < 0.001) and 0.74 (95% CI = 0.53-1.05, P = 0.09), respectively, when compared with methyl aminolevulinate photodynamic therapy. Compared with 5-fluorouracil, imiquimod showed a hazard ratio of 0.65 (95% CI 0.43-0.98, P = 0.04). In conclusion, 5 years after treatment, the results of this trial show that 5% imiquimod cream is superior to both methyl aminolevulinate photodynamic therapy and 5-fluorouracil cream in terms of efficacy for superficial basal cell carcinoma. We therefore consider 5% imiquimod cream as the first choice for noninvasive treatment in most primary superficial basal cell carcinomas.

A randomized controlled trial including 601 patients previously showed that the effectiveness of imiquimod and fluorouracil cream were not inferior to methyl aminolevulinate photodynamic therapy (MAL-PDT) in patients with superficial basal cell carcinoma after 1 year of follow-up. We now present the 3-year follow-up results. The probability of tumor-free survival at 3 years post-treatment was 58.0% for MAL-PDT (95% confidence interval [CI] = 47.8-66.9), 79.7% for imiquimod (95% CI = 71.6-85.7), and 68.2% for fluorouracil (95% CI = 58.1-76.3). The hazard ratio for treatment failure comparing imiquimod with MAL-PDT was 0.50 (95% CI = 0.33-0.76, P = 0.001). Comparison of fluorouracil with MAL-PDT and fluorouracil with imiquimod showed hazard ratios of 0.73 (95% CI = 0.51-1.05, P = 0.092) and 0.68 (95% CI = 0.44-1.06, P = 0.091), respectively. Subgroup analysis showed a higher probability of treatment success for imiquimod versus MAL-PDT in all subgroups with the exception of elderly patients with superficial basal cell carcinoma on the lower extremities. In this subgroup, the risk difference in tumor-free survival was 57.6% in favor of MAL-PDT. In conclusion, according to results at 3 years post-treatment, imiquimod is superior and fluorouracil not inferior to MAL-PDT in treatment of superficial basal cell carcinoma.

Aims: The reported incidence of metastasis from squamous cell carcinoma (SCC) of the skin and lip varies between 0.5% and 16%. Clinical and histopathological criteria have been proposed to identify tumours that may have an increased risk of metastasis. The aim of this study was to define such high-risk tumours, especially since the incidence of SCC of the skin is increasing. Methods and results: Histopathological features of metastasized skin and lip tumours and a matched group of non-metastasizing tumours were reassessed. Characteristics studied were: tumour width, excision margins, histological subtype, Clark level, Breslow depth, tumour differentiation, inflammation, perineural and angio-invasive growth, ulceration and desmoplasia. Data were statistically analysed separately for skin and labial lesions. Desmoplasia, Clark level, Breslow depth, maximum diameter, angio-invasion, grading, perineural invasion, plasma cells and eosinophilic inflammatory response proved to be statistically significantly related to metastasis of skin tumours. Breslow depth, plasma cells and grading appeared to be statistically significantly related to metastasis of SCC of the lips. Conclusions: A typical metastatic SCC showed: a tumour width of at least 15 mm, a vertical tumour thickness (¼ Breslow) of at least 2 mm, less differentiation, presence of desmoplasia and an inflammatory response with eosinophils and plasma cells.