Topical 5% Imiquimod for the Treatment of Superficial and Nodular Periocular Basal Cell Carcinoma: A Systematic Review of Clinical Outcomes, Safety, and Treatment Strategies.

BACKGROUND/OBJECTIVES: To evaluate the clinical and histological efficacy, safety, and cosmetic outcomes of 5% imiquimod (IMQ) cream, used in monotherapy or in combination, for periocular superficial and nodular basal cell carcinoma (BCC).

METHODS

A systematic search of MEDLINE, PubMed, and Google Scholar (inception-12 June 2025) identified studies reporting IMQ treatment of eyelid/periocular BCC. Randomized, nonrandomized and observational designs were eligible. Risk of bias was assessed with Cochrane RoB 2 or ROBINS-I, and certainty of evidence graded with GRADE.

RESULTS

Seven studies ( = 152 lesions) met the inclusion criteria. The pooled clinical-plus-histological clearance across case series was 82% (95% CI 72-90%). The single RCT ( = 27) reported 100% histological clearance for both IMQ and radiotherapy at 3 months, but IMQ produced superior cosmetic results. Combination immunocryosurgery (IMQ + cryotherapy) achieved 87.5% sustained remission at ≤5 years. Local adverse events-erythema, crusting, or conjunctivitis-occurred in ≥70% (85/122) of treated cases but were mild-to-moderate and self-limiting; systemic reactions were not reported. Forty-seven additional patients in a dedicated safety cohort showed only transient ocular irritation. The certainty of evidence was moderate for short-term clearance and low for long-term control because of small samples and heterogeneous follow-up.

CONCLUSIONS

IMQ 5% is a useful, tissue-sparing option for selected (superficial and nodular subtypes) periocular BCCs where surgery is contraindicated or cosmesis is paramount. Overall clearance is slightly lower than Mohs surgery but comparable to radiotherapy, and cosmetic outcomes are favorable. Larger, standardized RCTs with ≥3-year follow-up are needed to confirm durability, optimize dosing schedules, and validate patient-reported outcome measures.