Topical Treatment of Melanoma In Situ, Lentigo Maligna, and Lentigo Maligna Melanoma with Imiquimod Cream: A Systematic Review of the Literature

INTRODUCTION: The classical management of melanoma is surgery, but this can be challenging because of several factors, such as age, body area, lesion size, among others. Topical imiquimod may be a therapeutic option for the treatment of melanoma in situ and lentigo maligna melanoma due to its efficacy, tolerability, and non-invasiveness. The purpose of this systematic review is to assemble current evidence on the treatment of non-metastatic melanoma with topical imiquimod. METHODS: The PubMed/MEDLINE and Cochrane Library databases were searched as the primary sources using the main search terms “imiquimod” combined with “lentigo maligna” and “melanoma” with the command “AND.” Articles were identified, screened, and extracted for relevant data, following the PRISMA guidelines. RESULTS: A total of 87 studies covering 1803 lesions treated with imiquimod cream were identified and included in this sytematic review. Forty-nine studies were case reports, 16 were retrospective analyses, 3 were open label trials, six were case series; one study was a controlled randomized trial, one was a randomized trial, and one was a single-arm phase III trial. Because of the high number of low-evidence studies, the overall risk of bias resulted high. In 55 studies, imiquimod 5% was used in monotherapy as the primary treatment; only in one study was imiquimod 3.75% introduced. In most cases, the topical treatment was applied once daily, with the exception of nine cases where an increased daily dosage was prescribed. The total duration of the treatment regimen was extremely variable and depended on body area and tolerability, with differences among patients of the same study. In six studies, imiquimod was used as neoadjuvant therapy before the surgical excision, and in 11 studies it was used after surgery as complementary or adjuvant therapy. In total, 1133 of the 1803 (62.8%) lesions were reported to be cleared after the treatment, taking into account that not all of the patients completed the treatment. Of these 1133 lesions, histological clearance was achieved in 645 (56.9%) lesions and clinical clearance only was achieved in 490 (43.2%) lesions; relapse occurred in 107 lesions. CONCLUSIONS: The heterogeneity of the studies included in this systematic review precludes the drawing of any relevant conclusions regarding the application of imiquimod. Its efficacy in melanoma in situ and lentigo maligna melanoma has been demonstrated, but further evidence from controlled studies concerning the modalities is missing.