Topical Imiquimod for Lentigo Maligna: Survival Analysis of 103 Cases With 17 Years Follow-up

March 2021 | Volume 20 | Issue 3 | Features | 346 | Copyright © March 2021


Published online February 23, 2021

Meagan Chambers MS MSc MDa, Susan M. Swetter MDb, Catherine Baker MDa, Elizabeth Saunders MS PhDc,d, M. Shane Chapman MD MBAa,d

aGeisel School of Medicine at Dartmouth, Hanover, NH
bDepartment of Dermatology, Pigmented Lesion and Melanoma Program, Stanford University Medical Center and Cancer Institute, Stanford, CA
cThe Dartmouth Institute for Health Policy and Clinical Practice, Hanover, NH
dDepartment of Dermatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH

Abstract
Topical imiquimod 5% cream has been investigated as off-label primary or adjuvant treatment for melanoma in situ, lentigo maligna type (LM). Herein, we present the largest known case series of lentigo maligna treated with topical imiquimod, with up to 17 years of follow-up, and include a recurrence-free survival analysis. In this case series, 103 lesions were retrospectively evaluated for treatment response and recurrence following a course of topical imiquimod with or without tazarotene gel 0.1% pretreatment between January 1, 2002 and March 31, 2019, and prospectively followed through November 15, 2019. Over median follow-up of 5.1 years (mean = 6.2 years, S = 5.2 years, range, 0.08–17.1 years), including 29.1% LM with >10 years follow-up, we observed a response rate of 97.1% (100/103), with 8 local recurrences (8/100, 8.0%) developing at mean 2.9 years (SD: 2.7 years). Local recurrence was significantly associated with a history of failed excision (P= 0.001), <60 applications of imiquimod (P= 0.04) and partial clinical clearance (P= 0.0003). Recurrence-free survival analysis demonstrated significant risk-stratification for low and high-risk groups (P= 0.0001). Long term risk for recurrence showed significant differences among low- and high-risk cases, with low-risk cases demonstrating favorable long-term outcomes, comparable to conventional and staged surgery. Our observed low recurrence in a large case series with long-term follow-up suggests the efficacy of topical 5% imiquimod for LM and emphasizes the need for randomized control trials comparing imiquimod with, or as an adjunct to, surgical treatment.

J Drugs Dermatol. 2021;20(3):346-348. doi:10.36849/JDD.2021.5660

INTRODUCTION

Topical imiquimod 5% cream has been investigated as off-label primary or adjuvant treatment for melanoma in situ, lentigo maligna (LM) type, although long-term follow-up data are lacking.1 Herein, we present a novel survival analysis based on a case series of 103 LM type (n = 81) or atypical intradermal melanocytic proliferation lesions (consistent with early/evolving LM) (n = 22), who were treated with topical imiquimod and followed up to 17 years thereafter. We report recurrence free survival (RFS) following primary (nonsurgical) or adjuvant treatment (after excision with narrow histologic margins [<1 mm] or histologically positive margins without visible pigmentation) between January 1, 2002 and March 31, 2019 and followed through November 15, 2019.

Treatment protocol was based on evolving best practices; patients were offered surgical resection as first-line therapy or off-label topical imiquimod 5% cream as second-line therapy. Patients were instructed to apply imiquimod five times weekly (weekdays) for 12 weeks with or without pre-treatment using two weeks of daily tazarotene 0.1% gel in order to elicit an appropriate inflammatory response, including erythema and scale.

There were 51 females and 52 males, with average age of 69.9 years (S = 10.4 years, range, 38–92 years). Additional case information is available in Table 1. Primary treatment occurred in 71 cases (68.9%) while 32 cases (31.3%) used imiquimod for adjuvant therapy after surgical resection with margins positive or narrowly excised for LM. Median follow-up was 5.1 years (mean = 6.2 years, S = 5.2 years, range, 0.08–17.1 years); 47 cases (45.6%) had >5 years follow-up, and 30 (29.1%) had >10 years. Lesions were assessed histologically, with post-treatment biopsy one month after completion of treatment when possible (64% of cases), and clinically, including Wood’s lamp for residual pigmentation. Suspected recurrences were re-biopsied at the time of clinical suspicion.

The survival analysis assigned one point each to eight risk factors; age >65 years old, history of invasive melanoma at site of treatment, previous failed excision, no pre-treatment with