Rate of Recurrence of Lentigo Maligna Treated With Off-Label Neoadjuvant Topical Imiquimod, 5%, Cream Prior to Conservatively Staged Excision

Abstract

IMPORTANCE Staged excision of lentigo maligna (LM) often requires multiple stages and can result in significant cosmetic morbidity. Imiquimod cream has been used off-label as monotherapy in the treatment of LM and may be used in the neoadjuvant setting prior to staged excision as a strategy to reduce the size of the surgical margins required to confirm negative histologic margins. OBJECTIVE To examine the rate of recurrence of LM in patients treated with neoadjuvant topical imiquimod, 5%, cream prior to conservatively staged excisions. DESIGN, SETTING, AND PARTICIPANTS This was a retrospective medical record review of 334 patients with 345 biopsy-confirmed LM tumors from June 2004 to January 2012 who were treated with imiquimod prior to undergoing staged excisions at the University of Utah Medical Center and Huntsman Cancer Institute, large academic hospitals in Salt Lake City. INTERVENTIONS Patients were treated with off-label imiquimod, 5%, cream 5 nights per week for 2 to 3 months. Those deemed to have an inadequate inflammatory response were also treated with tazarotene, 0.1%, gel twice weekly. Conservatively staged excisions, beginning with 2-mm margins, were then performed. MAIN OUTCOMES AND MEASURES The rate of recurrence of LM after long-term follow-up. RESULTS Patients included 235 men (70%) and 99 women (30%) with a mean (SD) age of 67 (13) years. Patients were treated with imiquimod cream for a mean of 2.5 months prior to undergoing conservatively staged excisions. There were 12 local recurrences (a rate of 3.9%) with a mean time to recurrence of 4.3 years and a mean length of follow-up of 5.5 years. CONCLUSIONS AND RELEVANCE Neoadjuvant topical imiquimod, 5%, cream prior to conservatively staged excisions for LM allowed for negative histologic margins with a median final margin of 2 mm and a rate of recurrence similar to reported recurrence rates with standard staged excisions by either Mohs surgery or en face permanent sections.

<p>Lentigo Maligna: Clinical Presentation and Appropriate Management</p>

“…120 In addition, it may interfere with adenosine receptor pathways, increasing adenylyl cyclase activity; and may have proapoptotic activity against tumor cells. 13,121 Although it is off label, topical 5% imiquimod cream for LM has been extensively used, with variable results. [122][123][124][125] Complete histopathologic responses (based on targeted biopsies) range from 50% to 93%, recurrence rates range from 7.1% up to 50% and mean follow-up durations range from 6 months to 4.5 years.…”

“…128 Imiquimod as a neoadjuvant therapy has also been used in LM, demonstrating to be useful for decreasing the necessary margin for complete clearance. 121,129 In a study with 334 patients treated with imiquimod 5% cream 5 nights per week for 2 to 3 months followed by staged excisions, there was a median final margin of 2 mm with a recurrence rate of 3.9%, a mean time to recurrence of 4.3 years and a mean length of follow-up of 5.5 years. 121 Addition of tazarotene 0.1% gel to imiquimod cream 5% prior to staged excision has been assessed in a randomized trial of 47 patients in order to improve imiquimod's response.…”

“…121,129 In a study with 334 patients treated with imiquimod 5% cream 5 nights per week for 2 to 3 months followed by staged excisions, there was a median final margin of 2 mm with a recurrence rate of 3.9%, a mean time to recurrence of 4.3 years and a mean length of follow-up of 5.5 years. 121 Addition of tazarotene 0.1% gel to imiquimod cream 5% prior to staged excision has been assessed in a randomized trial of 47 patients in order to improve imiquimod's response. 129 Complete response after 12 weeks was observed histologically in 78% of lesions treated with combined therapy versus 64% treated with monotherapy (p = 0.17).…”

A Distinct Pretreatment Immune Gene Signature in Lentigo Maligna Is Associated with Imiquimod Response

“…Some develop a rapid florid inflammatory reaction to IMQ; others are slow to react or show no inflammatory reaction. Prior studies added topical retinoid treatments to hasten inflammatory responses and improve clearance rates for these patients (Donigan et al, 2018;Hyde et al, 2012). Patients who required 0.1% tazarotene in addition to IMQ to achieve an adequate inflammatory response in a neoadjuvant setting had a higher recurrence rate than those who developed adequate inflammation with IMQ alone, although this was not statistically significant (Donigan et al, 2018).…”

“…Prior studies added topical retinoid treatments to hasten inflammatory responses and improve clearance rates for these patients (Donigan et al, 2018;Hyde et al, 2012). Patients who required 0.1% tazarotene in addition to IMQ to achieve an adequate inflammatory response in a neoadjuvant setting had a higher recurrence rate than those who developed adequate inflammation with IMQ alone, although this was not statistically significant (Donigan et al, 2018). Furthermore, although inflammation is strongly associated with clinical clearance, some patients who lack apparent clinical inflammation have been shown to clear their disease histologically.…”