Abstract
BACKGROUND: There is compelling evidence that the incidence of melanoma in cigarette smokers is substantially lower than in non-smokers. However, the risks of both recurrence and death appear to be higher in smokers if melanoma does develop. The magnitude of these increased risks is poorly documented. This systematic review aimed to analyse melanoma survival outcomes among smokers compared to never-smokers using published studies, and report the magnitude of any survival differences. METHODS: Searches of Medline, Embase and Cochrane CENTRAL (to 11/03/2024) using terms for melanoma and smoking were conducted. Included studies were those reporting outcomes including disease severity at presentation, risk of death or adverse effects from treatment in smokers and never-smokers with melanoma. No study design or language restrictions were imposed. Risk of bias was assessed using the Newcastle-Ottawa tool. The review protocol was registered with PROSPERO (ID CRD42024518505). FINDINGS: Forty-six studies involving 164,166 melanoma patients, of whom 70,766 had smoked cigarettes, were identified. The pooled individual Hazard Ratios (HR) from multivariable analyses, showed that death from melanoma was 33% higher in current compared to never-smokers (HR 1.33, 95% CI 1.14-1.55, p = 0.0002, 13,971+ patients) with limited heterogeneity (I(2) 11%). However, former-smokers and never-smokers had very similar rates of death from melanoma (HR 1.04, 95% CI 0.94-1.14, p = 0.52, 16,307+ patients) with moderate heterogeneity (I(2) 63%). From univariable analyses, current-smokers had a higher risk of sentinel node-positivity compared to never-smokers (HR 1.35 95% CI 1.13, 1.62, p = 0.001, 5163 patients). Ever-smokers had a greater risk of complications from sentinel node biopsy (Odds Ratio (OR) 2.0 95% CI 1.41-2.85, p = 0.0001, 3745 patients) and lymph node dissection (OR 1.7, 95% CI 1.23-2.20, p = 0.0007, 4596 patients) than never-smokers based on risks from multivariable analyses. INTERPRETATION: Current smokers are more likely to die from their melanoma than never-smokers, while former-smokers appear to have similar risks to never-smokers. Smokers have higher risks of sentinel node-positivity and of complications from node surgery. Study limitations included reliance on self-reporting of smoking status. In only seven studies did patients receive modern systemic therapies, limiting the ability to assess their relative efficacy in smokers and non-smokers. FUNDING: None.