Surgical Excision Versus Photodynamic Therapy and Topical 5-fluorouracil in Treatment of Bowen's Disease

Summary

There is limited quality research on the effectiveness of treatments in Bowen's disease (BD). Patient and lesion characteristics, patient preferences and costs should be considered when choosing therapy. Surgical excision (SE), photodynamic therapy (PDT) and 5-fluorouracil (5FU) are mentioned as treatment options in guidelines. However no clear and evidence based recommendations are made in terms of effectiveness. Objective: The aim of this study is 1) to evaluate the (cost)effectiveness of 5FU and PDT compared to SE in BD and 2) to compare the effectiveness of 5FU with that of PDT. With a better understanding of the (cost)effectiveness of alternative treatment options, the investigators will supply the necessary evidence for national and international guidelines, to achieve more uniformity in treatment of BD. Study design: Randomized controlled non-inferiority multicenter trial. Study population: Patients ≥18 years, with a histological proven primary lesion of Bowen's disease, visiting Maastricht University Medical Centre, Catharina hospital Eindhoven, VieCuri MC Venlo or Zuyderland Medical Centre Heerlen. Intervention: One group undergoes SE with a 5mm safety margin followed by routine histological examination. The other group receives PDT with application of methyl aminolevulinate (MAL) cream followed by two illuminations with a one-week interval. The third group receives 5FU cream, which has to be applied by the patient twice daily for 4 weeks. Main study parameters/endpoints: The primary outcome is the proportion of patients with sustained clearance at 12 months post-treatment. Secondary outcomes are proportion of patients with clearance at 3 months, the long-term probability of sustained clearance, cost-effectiveness, patient satisfaction, patient preferences, compliance, side effects and cosmetic outcome. Post-treatment, patients will be asked to answer a short questionnaire regarding side effects, experience with the treatment and satisfaction.

Timeline

Start

2019-05-27

Primary completion

2022-03-02

Completion

2024-12-12

Publications

• Background Holterhues C, Vries Ed, Louwman MW, Koljenovic S, Nijsten T. Incidence and trends of cutaneous malignancies in the Netherlands, 1989-2005. J Invest Dermatol. 2010 Jul;130(7):1807-12. doi: 10.1038/jid.2010.58. Epub 2010 Mar 25.
• Background Arlette JP, Trotter MJ. Squamous cell carcinoma in situ of the skin: history, presentation, biology and treatment. Australas J Dermatol. 2004 Feb;45(1):1-9; quiz 10. doi: 10.1111/j.1440-0960.2004.00025.x.
• Background Bowen JT. Centennial paper. May 1912 (J Cutan Dis Syph 1912;30:241-255). Precancerous dermatoses: a study of two cases of chronic atypical epithelial proliferation. By John T. Bowen, M.D., Boston. Arch Dermatol. 1983 Mar;119(3):243-60. No abstract available.
• Background Shimizu I, Cruz A, Chang KH, Dufresne RG. Treatment of squamous cell carcinoma in situ: a review. Dermatol Surg. 2011 Oct;37(10):1394-411. doi: 10.1111/j.1524-4725.2011.02088.x. Epub 2011 Jul 18.
• Background Kao GF. Carcinoma arising in Bowen's disease. Arch Dermatol. 1986 Oct;122(10):1124-6. No abstract available.
• Background PETERKA ES, LYNCH FW, GOLTZ RW. An association between Bowen's disease and internal cancer. Arch Dermatol. 1961 Oct;84:623-9. doi: 10.1001/archderm.1961.01580160087015. No abstract available.
• Background Bichakjian CK, Olencki T, Aasi SZ, Alam M, Andersen JS, Berg D, Bowen GM, Cheney RT, Daniels GA, Glass LF, Grekin RC, Grossman K, Higgins SA, Ho AL, Lewis KD, Lydiatt DD, Nehal KS, Nghiem P, Olsen EA, Schmults CD, Sekulic A, Shaha AR, Thorstad WL, Tuli M, Urist MM, Wang TS, Wong SL, Zic JA, Hoffmann KG, Engh A. Basal Cell Skin Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2016 May;14(5):574-97. doi: 10.6004/jnccn.2016.0065.
• Background Bath-Hextall FJ, Matin RN, Wilkinson D, Leonardi-Bee J. Interventions for cutaneous Bowen's disease. Cochrane Database Syst Rev. 2013 Jun 24;2013(6):CD007281. doi: 10.1002/14651858.CD007281.pub2.
• Background Bonerandi JJ, Beauvillain C, Caquant L, Chassagne JF, Chaussade V, Clavere P, Desouches C, Garnier F, Grolleau JL, Grossin M, Jourdain A, Lemonnier JY, Maillard H, Ortonne N, Rio E, Simon E, Sei JF, Grob JJ, Martin L; French Dermatology Recommendations Association (aRED). Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma and precursor lesions. J Eur Acad Dermatol Venereol. 2011 Dec;25 Suppl 5:1-51. doi: 10.1111/j.1468-3083.2011.04296.x. No abstract available.
• Background Hansen JP, Drake AL, Walling HW. Bowen's Disease: a four-year retrospective review of epidemiology and treatment at a university center. Dermatol Surg. 2008 Jul;34(7):878-83. doi: 10.1111/j.1524-4725.2008.34172.x.
• Background Morley GL, Matthews JH, Verpetinske I, Thom GA. A Comparative Study Examining the Management of Bowen's Disease in the United Kingdom and Australia. Dermatol Res Pract. 2015;2015:421460. doi: 10.1155/2015/421460. Epub 2015 Sep 9.
• Background Morton CA, Birnie AJ, Eedy DJ. British Association of Dermatologists' guidelines for the management of squamous cell carcinoma in situ (Bowen's disease) 2014. Br J Dermatol. 2014 Feb;170(2):245-60. doi: 10.1111/bjd.12766. No abstract available.
• Background Overmark M, Koskenmies S, Pitkanen S. A Retrospective Study of Treatment of Squamous Cell Carcinoma In situ. Acta Derm Venereol. 2016 Jan;96(1):64-7. doi: 10.2340/00015555-2175.
• Background Szeimies RM, Karrer S, Backer H. [Therapeutic options for epithelial skin tumors. Actinic keratoses, Bowen disease, squamous cell carcinoma, and basal cell carcinoma]. Hautarzt. 2005 May;56(5):430-40. doi: 10.1007/s00105-005-0950-5. German.
• Background Westers-Attema A, van den Heijkant F, Lohman BG, Nelemans PJ, Winnepenninckx V, Kelleners-Smeets NW, Mosterd K. Bowen's disease: A six-year retrospective study of treatment with emphasis on resection margins. Acta Derm Venereol. 2014 Jul;94(4):431-5. doi: 10.2340/00015555-1771.
• Background Jansen MH, Appelen D, Nelemans PJ, Winnepenninckx VJ, Kelleners-Smeets NWJ, Mosterd K. Bowen's Disease: Long-term Results of Treatment with 5-Fluorouracil Cream, Photodynamic Therapy or Surgical Excision. Acta Derm Venereol. 2018 Jan 12;98(1):114-115. doi: 10.2340/00015555-2777. No abstract available.
• Background Arits AH, Mosterd K, Essers BA, Spoorenberg E, Sommer A, De Rooij MJ, van Pelt HP, Quaedvlieg PJ, Krekels GA, van Neer PA, Rijzewijk JJ, van Geest AJ, Steijlen PM, Nelemans PJ, Kelleners-Smeets NW. Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: a single blind, non-inferiority, randomised controlled trial. Lancet Oncol. 2013 Jun;14(7):647-54. doi: 10.1016/S1470-2045(13)70143-8. Epub 2013 May 15.
• Background Morton CA, McKenna KE, Rhodes LE; British Association of Dermatologists Therapy Guidelines and Audit Subcommittee and the British Photodermatology Group. Guidelines for topical photodynamic therapy: update. Br J Dermatol. 2008 Dec;159(6):1245-66. doi: 10.1111/j.1365-2133.2008.08882.x. Epub 2008 Oct 13.
• Background M Versteegh M, M Vermeulen K, M A A Evers S, de Wit GA, Prenger R, A Stolk E. Dutch Tariff for the Five-Level Version of EQ-5D. Value Health. 2016 Jun;19(4):343-52. doi: 10.1016/j.jval.2016.01.003. Epub 2016 Mar 30.
• Background Briggs AH, Wonderling DE, Mooney CZ. Pulling cost-effectiveness analysis up by its bootstraps: a non-parametric approach to confidence interval estimation. Health Econ. 1997 Jul-Aug;6(4):327-40. doi: 10.1002/(sici)1099-1050(199707)6:43.0.co;2-w.
• Moermans MMG, Ahmady S, Nelemans PJ, Arits AHMM, Kessels JPHM, van Pelt HPA, Kelleners-Smeets NWJ, Mosterd K. Surgical excision versus topical 5% 5-fluorouracil and photodynamic therapy in the treatment of Bowen's disease: Long-term results of a multicenter randomized controlled trial. J Am Acad Dermatol. 2026 May;94(5):1447-1453. doi: 10.1016/j.jaad.2025.12.034. Epub 2025 Dec 12.
• Ahmady S, van Riel CAM, Kelleners-Smeets NWJ, Mosterd K, Essers BAB. Cost-Effectiveness of Photodynamic Therapy and 5-Fluorouracil Cream versus Surgical Excision in Treatment of Bowen's Disease: A Trial-Based Economic Evaluation. Dermatology. 2025;241(5-6):489-498. doi: 10.1159/000548431. Epub 2025 Sep 11.

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