Study Results Show Current Smoking Increases the Risk of Death from Melanoma

Smoking at the time of melanoma diagnosis may be linked to a higher risk of death from cutaneous melanoma, according to the results of a post-hoc study recently published in JAMA Network Open. Smoking is already a known carcinogen linked to bladder and lung cancer, and this study provides evidence that it is an independent risk factor of melanoma-associated death across different subgroups.

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“Because smoking could be considered a risk factor for disease progression, increased vigilance in the management of patients who smoke may be warranted,” authors wrote in the paper.

Previous studies have evaluated the impact of smoking on melanoma survival outcomes, but findings are inconsistent. Investigators conducted a prospective post-hoc analysis of prognostic and smoking data that were originally collected from 2 large, randomized trials (Multicenter Selective Lymphadenectomy Trials [MSLT-I and MSLT-II]).

Patients in the trials were diagnosed with clinical stages 1 or 2 melanoma (Breslow thickness of 1.00 mm or greater or Clark level IV to V). Of the 6279 patients aged 18 to 75 years with available data, 1077 (17.2%) were current smokers, 1694 (27.0%) were former smokers, and 3508 (55.9%) were never smokers.

Risk of melanoma-associated death was highest among current smokers (hazard ratio [HR], 1.48 [95% CI, 1.26-1.75]; P < .001). There was no link between melanoma-associated death and being a former smoker.

A subgroup analysis evaluated the impact of sentinel lymph node biopsy (SLNB) on risk of melanoma-associated death. Primary tumor ulceration is the number 1 risk factor associated with death from melanoma among patients with SLNB-negative status, and smoking is the second highest risk factor associated with melanoma-associated death.

Of the SLNB subgroups, patients with SLNB-negative disease who smoked had the greatest risk of death from melanoma (HR, 1.85 [95% CI, 1.35-2.52]; P < .001), despite smoking being more commonly associated with SLNB-positive status. Additionally, patients with SLNB-negative status who smoked 20 or more cigarettes per day had a 2-times higher risk of death from melanoma compared to nonsmokers (HR, 2.06 [95% CI, 1.36-3.13]; P < .001).

Besides SLNB positivity, other factors that were associated with smoking included male sex, younger age, trunk site, tumor thickness, and tumor ulceration.

Study limitations include combining the findings from 2 separate trials; relying on single time point and self-reported smoking status; combining individuals who recently or distantly stopped smoking into 1 “former smoker” group; and using data from a cohort who did not have access to modern checkpoint blockade or targeted therapies. Continued research is needed to strengthen findings of an association between current smoking and melanoma-associated death.

“The presence of the strong observed association, despite this potential confounder, argues for the significance of smoking specifically in relationship to melanoma progression,” authors wrote in the paper. “Patients with early-stage melanoma should be strongly encouraged to quit[smoking] as a potential mitigation strategy for disease progression.”

REFERENCE

Jackson KM, Jones PC, Fluke LM. Smoking Status and Survival in Patients With Early-Stage Primary Cutaneous Melanoma. JAMA Netw Open. 2024;7(2):e2354751. doi:10.1001/jamanetworkopen.2023.54751