Lentigo maligna (LM) is an in situ melanoma arising on sun-damaged skin. For some patients, radiotherapy and topical imiquimod are established alternatives to surgery. The RADICAL trial aimed to assess efficacy, safety, cost-effectiveness, and patient-reported health-related quality of life (HRQL) of both treatments.
A multi-institutional (8 centres), phase III RCT was conducted between August 2015 and November 2021, randomising patients 1:1 to radiotherapy or imiquimod. The primary endpoint was treatment failure at 27 months post-randomisation. Secondary endpoints included 9-month response, development of invasive disease, toxicity, and HRQL. Self-reported symptoms, emotional and functional impacts were assessed using Skindex questionnaires at baseline and four follow-up timepoints. Blinded dermatologist ratings of standardised photographs assessed 2-year cosmetic outcomes. A cost analysis estimated direct medical costs and indirect costs from both the healthcare system and societal perspectives.
Across 126 randomised patients, response rates were 95% at 6 months in both groups. Treatment failure rates were low (20.7% vs 10.0%; OR 2.35, 95% CI 0.82–6.75, p=0.11), with no statistically significant difference, given the trial's underpowering (stopped due to the pandemic). Both treatments were well tolerated, with predominantly grade 1–2 acute skin toxicity. Severe impacts on HRQL peaked at 3 months (40% skin symptoms, <20% functional and emotional domains) and declined to <7% across all domains by 27 months. Emotional distress reduced significantly from baseline (39%) to 27 months (8%). Cosmetic outcomes favoured imiquimod (p=0.036). Healthcare system costs were substantially higher for radiotherapy (US$2,673 vs US$73 per patient), requiring more visits and greater productivity and travel costs. Societal costs were US$4,379 for radiotherapy versus US$698 for imiquimod.
Imiquimod and RT produce good short-term responses for LM, with a non-significant trend favouring imiquimod at 27 months. Imiquimod offers superior cosmetic outcomes and is substantially less resource-intensive. These findings should inform patient-centred shared decision-making and supportive care planning. I will discuss what's next.