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

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.