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 .