5-fluorouracil 5% cream for squamous cell carcinoma in situ: Factors impacting treatment response.

Lin, Christine P; Kibbi, Nour; Bandali, Tarek; Hirotsu, Kelsey; Aasi, Sumaira Z · J Am Acad Dermatol · 2025

retrospective_cohort · Level III

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Abstract

Complete clinical response (CCR) rates for squamous cell carcinoma in situ (SCCis) treated with 5-fluorouracil (5-FU) 5% cream range from 27% to 85%. Factors associated with CCR are not well-established. Retrospective review of biopsy-proven primary SCCis diagnosed between May 1, 2019, and April 30, 2020, and treated with 5-FU 5% cream. Disease status at follow-up was recorded, with treatment failure defined as persistent or recurrent disease. The study included 149 SCCis cases, including 33.6% (50/149) arising in the context of immunosuppression. Eighteen cases failed treatment (10 persistent disease, 8 recurrent disease). By tumor size, CCR was noted in 128/144 (88.9%) tumors measuring <2 centimeters in diameter and 3/5 tumors ≥2 centimeters (60.0%, P = .051). By treatment duration, CCR was observed in 4/7 (57.1%) tumors treated for <2 weeks, 72/83 (86.7%) tumors treated for 2 to <4 weeks, and 55/59 (93.2%) tumors treated for ≥4 weeks (P = .019). On multivariate analysis, treatment failure was significantly associated with shorter treatment durations (odds ratio: 0.26; P = .007) and increasing tumor size (odds ratio: 2.40; P = .037). Shorter treatment duration and larger lesion size were significantly associated with failure of 5-FU in SCCis. Immunosuppression and anatomic location were not significant factors, supporting 5-FU use for SCCis in the immunosuppressed population and highlighting its versatility irrespective of anatomic location.

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