Imiquimod Cream Preceded by Superficial Curettage vs Surgical Excision for Nodular Basal Cell Carcinoma: A Secondary Analysis of a Randomized Clinical Trial.

Abstract

Background: Interest in noninvasive treatment of basal cell carcinoma (BCC) has been increasing. For superficial BCC, it has been demonstrated that imiquimod cream, 5%, has high long-term efficacy, but for nodular BCC (nBCC), long-term evidence is sparse.

Objectives: To evaluate whether superficial curettage (SC) followed by imiquimod cream, 5%, is noninferior to surgical excision (SE) in nBCC after 5 years of treatment.

Design, setting, and participants: In this secondary analysis of the noninferiority Surgery Versus Combined Treatment With Curettage and Imiquimod for Nodular Basal Cell Carcinoma (SCIN) randomized clinical trial, patients with a primary nBCC of 4 to 20 mm were assigned to either SC plus imiquimod, 5%, or SE between January 1, 2016, to November 30, 2017, at 2 outpatient dermatology departments in the Netherlands. The primary outcome of the SCIN trial was the 1-year probability of remaining free from treatment failure; the prespecified secondary trial outcomes were the probability after 5 years of follow-up, completed September 7, 2022. Both an intention-to-treat analysis and per-protocol analysis were planned.

Intervention: SC plus imiquimod vs SE.

Main outcomes and measures: The 5-year probability of remaining free from treatment failure (ie, freedom from recurrence; with 95% CI) was estimated with Kaplan-Meier analysis using data on treatment response from 3 planned follow-up visits at 3 months and 1 and 5 years after the end-of-treatment date. Additional analyses accounting for death as competing risk were also performed.

Results: A total of 145 patients (77 [53.1%] male; median age, 68 [IQR, 31-89] years) with a primary, histologically proven nBCC were randomized to treatment with SC plus imiquimod (n = 73) or SE (n = 72). In total, 15 treatment failures occurred in the SC plus imiquimod group (5 treatment failures occurred between 1 and 5 years after treatment) and 1 in the SE group. The 5-year probability of remaining free from treatment failure was 77.8% (95% CI, 65.7%-86.0%) after SC plus imiquimod and 98.2% (95% CI, 88.0%-99.8%) after SE. The relative risk of treatment failure was 15.93 (95% CI, 2.10-120.64). The 95% CI does not exclude the noninferiority margin of 5.22. Death due to causes unrelated to BCC occurred in 20 patients, and the subhazard ratio from competing risk regression was 16.16 (95% CI, 2.18-119.72).

Conclusions: This secondary analysis of a randomized clinical trial found that although it cannot be concluded that SC plus imiquimod is noninferior to SE, SC plus imiquimod was substantially less effective at 5 years after treatment. Most treatment failures occurred in the first year after treatment, and the probability of tumor-free survival 5 years after treatment with SC plus imiquimod was still 77.8%. The information in this trial can be used to counsel patients on the relative benefits and trade-offs of the different treatment options for nBCC.

Trial registration: ClinicialTrials.gov Identifier: NCT02242929.