Long-Term Outcomes of Topical 5% Imiquimod Treatment for Lentigo Maligna: A Systematic Review

Lentigo maligna (LM) is a melanoma in situ frequently located on sun-exposed areas. While surgery is the standard of care, topical 5% imiquimod has emerged as a non-invasive alternative for patients unsuitable for surgery. However, existing literature often lacks long-term follow-up. This systematic review aims to assess the long-term effectiveness and safety of imiquimod in LM, focusing on studies with ≥ 48 months of follow-up.

A comprehensive search was conducted in MEDLINE (PubMed) and the Cochrane Library up to July 2025. Inclusion criteria comprised original studies reporting on LM treated with 5% imiquimod with ≥ 48 months of follow-up.

Six studies (422 patients) met the inclusion criteria: one prospective and five retrospective studies. Median follow-up ranged from 49 to 205 months. Clinical clearance rates varied between 63.6% and 97.1%, with recurrence rates ranging from 0% to 20.7%. Histological clearance was inconsistently confirmed. Progression to lentigo maligna melanoma (LMM) was infrequent (9/422). One retrospective study (n = 111) reported melanoma-specific survival at 10 years as 100% (95% CI 90.5-100%). The presence of a robust local inflammatory response was consistently associated with improved outcomes. Adverse effects were mostly mild and self-limiting. Overall evidence certainty was moderate to low.

This review provides evidence that 5% imiquimod may offer durable responses for LM, particularly in patients who develop a marked inflammatory reaction. Nevertheless, recurrence and occasional progression to LMM underscore the need for long-term monitoring, ideally combining clinical, dermoscopic and histological assessment. Lack of standardized treatment protocols and heterogeneous definitions of response limit comparability between studies.

Topical 5% imiquimod may be a viable long-term treatment option for selected patients with LM, although the evidence is scarce and mostly of low quality. A strong local inflammatory response appears predictive of clinical success. Given the potential for late recurrence and risk of progression to LMM, long-term structured follow-up is essential. Future prospective studies with uniform protocols are warranted.