Risk factors for subsequent primary melanoma in patients with previous melanoma: a systematic review and meta-analysis

Background Compared with the general population, people with a previous melanoma are at increased risk of developing another primary melanoma. Understanding the risk factors associated with multiple primary melanomas can inform patient education and tailored surveillance.Objectives To examine the risk factors for subsequent primary melanoma in people with a previous melanoma, by conducting a systematic review and meta-analysis of the available data.Methods A systematic literature search was conducted in CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Embase and MEDLINE. Studies that reported a risk estimate or raw frequencies and conducted between 1982 and August 2022 were included. Adjusted risk estimates were prioritized over univariable risk estimates. PRISMA reporting guidelines were followed. Random effects meta-analysis was conducted to derive pooled estimates. Quality assessment was conducted by two researchers using the Newcastle-Ottawa scale. GRADE was used to rate the certainty and quality of the evidence.Results Data from 27 studies involving 413 181 participants were pooled and analysed. Risk factors assessed included age and sex, environmental, lifestyle, phenotypic, genetic and histopathological factors, and there was wide variation in how they were categorized and analysed. Independent risk factors identified from pooled analyses included male sex [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.40-1.53], increasing age per 10 years (HR 1.19, 95% CI 1.14-1.24), light skin colour (HR 1.44, 95% CI 1.23-1.70), family history [odds ratio (OR) 1.79, 95% CI 1.25-2.56], CDKN2A mutation (OR 5.29, 95% CI 2.70-10.37), a high or moderate naevus count [OR 2.63 (95% CI 1.61-4.30) and OR 1.64 (95% CI 1.07-2.51), respectively], one or more atypical naevi (OR 3.01, 95% CI 1.52-5.97), first lesions occurring on the head or neck, lentigo maligna subtype (HR 1.16, 95% CI 1.15-1.17), other subtype (HR 1.14, 95% CI 1.03-1.27) and inadequate sun protection (HR 1.85, 95% CI 0.98-3.50). Based on the GRADE criteria, there was high to very low confidence in the pooled effect estimates.Conclusions This meta-analysis identified several consistent, independent risk factors for the development of subsequent primary melanoma. These findings will help stratify the risk of subsequent melanoma, tailor skin-check schedules and inform patient education. Understanding the risk factors associated with multiple primary melanomas can inform patient education and tailored surveillance in this at-risk group. We conducted a systematic review and meta-analysis involving 413 181 participants to examine risk factors for subsequent primary melanoma. Independent risk factors identified from pooled analyses included male sex, increasing age, light skin, family history of melanoma, CDKN2A mutation, a high or moderate naevus count, atypical naevi, first lesions occurring on the head and neck, lentigo maligna subtype, other subtype and inadequate sun protection.