Acta Dermato-Venereologica issue 50:1 98-1CompleteContent | Page 26

114 SHORT COMMUNICATION

Advances in dermatology and venereology Acta Dermato-Venereologica

Bowen’ s Disease: Long-term Results of Treatment with 5-Fluorouracil Cream, Photodynamic Therapy or Surgical Excision

Maud H. E. JANSEN 1, 2, Diebrecht APPELEN 3, Patty J. NELEMANS 4, Veronique J. WINNEPENNINCKX 5, Nicole W. J. KELLENERS- SMEETS 1, 2 and Klara MOSTERD 1, 2 Departments of 1 Dermatology and 5 Pathology, Maastricht University Medical Centre, P. Debyelaan 25, NL-6229 HX Maastricht, 2 GROW Research Institute for Oncology and Developmental Biology, 3 Department of Dermatology, Radboud Medical Centre, Nijmegen, and 4 Department of Epidemiology, Maastricht University, Maastricht, The Netherlands. E-mail: maud. jansen @ mumc. nl Accepted Aug 23, 2017; Epub ahead of print Aug 23, 2017

Bowen’ s disease( BD) is an intra-epidermally located squamous cell carcinoma( SCC) in situ, which occurs mostly on sun-exposed areas( 1 – 4). Several treatment modalities are described, including surgical excision( SE), imiquimod, 5-fluorouracil( 5-FU), photodynamic therapy( PDT), curettage, and cryotherapy( 4 – 8). The major advantage of SE is histological evaluation. However, SE comes with complications and scarring. Topical therapies are less invasive, often have cosmetic superiority, enable treatment of multiple tumours at once and might be preferable for tumours in locations where excision may be complicated by delayed wound healing.

The clinical efficacy of 5-FU and PDT, compared with SE, was analysed in a large study population at our department.

MATERIALS AND METHODS

Patients were retrospectively selected from the histological database from the Pathology Department of the Maastricht University Medical Centre( MUMC +), Maastricht, The Netherlands. Patients eligible for inclusion were those diagnosed with a histologically confirmed BD between 1 January 2008 and 31 December 2013 and treated by dermatologists. Exclusion criteria were: patients with BD on genitalia / mucous membranes or lesions found nearby an invasive skin cancer. Patient, tumour, and treatment characteristics were reviewed from medical records. The study was approved by the local Medical Ethics Committee.

Tumours were excised with a 5-mm safety margin, followed by routine histological examination. For PDT, application of aminolaevulinic acid( ALA) or methylaminolevulinate( MAL) cream was followed by illumination( Aktilite ®, 630 nm; Galderma, SA, Lausanne, Switzerland) and repeated after one week( 4, 9). For 5-FU, patients applied 5-FU 5 % cream twice daily for 4 weeks( 4)

Treatment failure was defined as clinical evidence of residual tumour, tumour recurrence or progression into an invasive tumour. Tumour presence or keratosis at the site of the initial tumour on first( 3 months) follow-up visit following 5-FU or PDT was considered residual tumour. For SE, information on residual lesions was obtained from the pathology report. Recurrence was defined as a new proliferation at the site of the original tumour. In cases of doubt, the suspicion was histopathologically confirmed.

Descriptive results are presented as numbers and percentages for categorical variables and as means(± standard deviation) for continuous variables. The χ 2 test and one-way analysis of variance( ANOVA) were used to test differences between treatment groups for statistical significance. Cumulative probability of treatment failure at 1, 2 and 5-years follow-up was calculated with Kaplan – Meier analysis and the log-rank test was used for comparison between treatments. Follow-up ended at the date of diagnosis of treatment failure or at the date of last follow-up visit.

Cox regression analysis was performed to calculate hazard ratios( HR) with 95 % confidence intervals( 95 % CI) using SE as the reference group. Variables coding for relevant baseline characteristics( age, sex, lesion diameter, tumour localization and use of immunosuppressive medication) were entered as independent variables to adjust for potential confounding due to differences in baseline characteristics between treatment groups. Missing values on tumour diameter were dealt with using multiple imputation techniques. p-values ≤ 0.05 were considered to indicate statistical significance. Data analyses were performed with SPSS 23.0( IBM Corp., Armonk, NY, USA) and Stata Version 14( Stata Corp, College Station, TX, USA).

RESULTS

A total of 1,688 histological reports on BD were identified. Of those, 847 cases were excluded( Fig. S1 1).

A total of 841 tumours in 608 patients were included. Baseline characteristics are shown in Table SI 1. Most patients were treated with either SE( n = 296) or PDT( n = 241). 5-FU was used in 46 patients. The majority of patients( 78.6 %) had only one BD. Median follow-up was 18 months( range 0 – 87 months).

Cumulative probabilities of treatment failure are summarized in Table I. The number of recurrences following 5-FU remained more or less stable after one year, whereas recurrences post-PDT developed even after 3 years. Crude and adjusted hazard ratios( HRs) for PDT and 5-FU compared with SE are summarized in Table SII 1. After adjustment for differences in baseline characteristics between the treatment groups, PDT is associated with a significantly higher risk of treatment failure than SE( HR 2.71 with 95 % CI: 1.52 – 4.83). 5-FU also showed

1 https:// www. medicaljournals. se / acta / content / abstract / 10.2340 / 00015555-2777

Table I. Cumulative probability of treatment failure after surgical excision( SE) vs. photodynamic therapy( PDT) vs. 5-fluorouracil( 5-FU), based on Kaplan – Meier survival analysis

doi: 10.2340 / 00015555-2777 Acta Derm Venereol 2018; 98: 114 – 115

This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica.