Why we chose this paper?

Lentigo maligna (LM) is a melanoma in situ occurring mainly on sun-damaged head and neck skin in elderly patients. Surgery is the gold standard, but many individuals are unsuitable due to lesion size, anatomical site, or comorbidities. Until now, there has been no randomized evidence comparing nonsurgical options. This trial provides much-needed high-quality data on radiotherapy and imiquimod, two commonly used alternatives.

Study aim and design

This multicenter, open-label, phase 3 randomized trial (ClinicalTrials.gov NCT02394132) recruited 126 patients with biopsy-proven LM unsuitable for surgery between 2015 and 2021 across Australia, New Zealand, and Brazil. Participants were randomized 1:1 to radiotherapy (fractionated regimens equivalent to 56 Gy) or topical imiquimod 5% applied five days weekly for 12 weeks. The primary endpoint was treatment failure (recurrence or persistence) at 24 months. Secondary endpoints included 6-month histological response, development of invasive melanoma, toxicity, and health-related quality of life (HRQL).

What were the main findings?

• Response rates: Both groups achieved 95% histological clearance at 6 months.

• Treatment failure at 24 months: 20.7% in the radiotherapy group vs 10% in the imiquimod group (OR 2.35; 95% CI, 0.82–6.75; p=0.11). Differences were not statistically significant.

• Progression: No patients developed invasive melanoma during follow-up.

• Tolerability: Both treatments were well tolerated, with mainly grade 1–2 skin toxicity. Radiotherapy caused more short-term dermatitis; imiquimod reactions varied with dose adjustments.

• Quality of life: No long-term HRQL differences between groups. Emotional well-being improved significantly after treatment in both arms.

Limitations and applicability

The trial was underpowered due to early closure during the COVID-19 pandemic and had relatively short follow-up for a slow-growing tumor. Treatment allocation was unblinded, which may have influenced biopsy decisions. Despite these limitations, the results support radiotherapy and imiquimod as effective, safe nonsurgical options when surgery is not feasible.

What’s the take home message?

For patients with complex lentigo maligna who cannot undergo surgery, both radiotherapy and imiquimod are valid, well-tolerated alternatives with high clearance rates and preserved quality of life.