Surgical excision versus topical 5% 5-fluorouracil and photodynamic therapy in treatment of Bowen's disease: a multicenter randomized controlled trial

BACKGROUND: Randomized controlled trials comparing the effectiveness of 5-fluorouracil cream, methylaminolevulinate photodynamic therapy (MAL-PDT) and surgical excision in patients with Bowen's disease are lacking. background METHODS: In this multicenter non-inferiority trial, patients with a histologically proven Bowen's disease of 4-40mm were randomly assigned to excision with 5mm margin, 5% 5-fluorouracil cream twice daily for four weeks, or two sessions of MAL-PDT with one week interval. The primary outcome was the proportion of patients with sustained clearance at 12 months after treatment. A non-inferiority margin of 22% was used. RESULTS: Between May 2019 and January 2021, 250 patients were randomized. The proportion of patients with sustained clearance was 97.4% (75/77) after excision, 85.7% (66/77) after 5-fluorouracil and 82.1% (64/78) after MAL-PDT. Absolute differences were -11.7% (95% CI -18.9 to -4.5; P=0.0049) for 5-fluorouracil versus excision and -15.4% (95% CI -23.1 to -7.6; P=0.00078) for MAL-PDT versus excision. Both non-invasive treatments significantly more often led to good or excellent cosmetic outcome. results CONCLUSIONS: Based on our predefined non-inferiority margin of 22%, 5-fluorourcail is non-inferior to excision and associated with better cosmetic outcome. For MAL-PDT non-inferiority to excision cannot be concluded. Therefore, 5-fluorouracil should be preferred over excision and MAL-PDT in treatment of Bowen's disease.