Smoking Tied to Increased Mortality From Early-Stage Melanoma

Patients with clinically localized primary cutaneous melanoma who smoked cigarettes at the time of diagnosis had an increased risk of melanoma-associated mortality, a cohort study showed.

In a post hoc analysis of data derived from two randomized trials involving more than 6,000 patients, current smoking was associated with a 48% greater risk of melanoma-associated death compared with never smoking (HR 1.48, 95% CI 1.26-1.75, P<0.001), reported Katherine M. Jackson, MD, of Saint John's Cancer Institute in Santa Monica, California, and colleagues.

Notably, former smoking showed no association (HR 1.03, 95% CI 0.89-1.20, P=0.68), they detailed in JAMA Network Open.

Furthermore, a heavier smoking habit was associated with worse outcomes. Patients who smoked 20 or more cigarettes a day had an increased risk of melanoma-associated death (HR 1.63, 95% CI 1.33-2.01, P<0.001) compared with non-smokers, as did those who smoked 10 to 19 cigarettes a day (HR 1.48, 95% CI 1.13-1.93, P=0.004). However, light smokers (<10 cigarettes a day) had no increased risk (HR 1.13, 95% CI 0.81-1.58, P=0.47).

“Because smoking could be considered a risk factor for disease progression, increased vigilance in the management of patients who smoke may be warranted,” the authors wrote. Moreover, while the association of continued smoking with melanoma-associated mortality wasn’t addressed in the study, “it seems prudent to recommend smoking cessation to patients with melanoma at the time of diagnosis,” they suggested.

In a commentary accompanying the study, Mary S. Brady, MD, of Memorial Sloan Kettering Cancer Center in New York City, noted that some studies have shown that cigarette smoking is actually associated with a lower incidence of melanoma.

However, “the association of smoking with melanoma survival has not been determined,” Brady wrote. “We did not really need another reason to recommend against smoking, but here we have it. Congratulations to the investigators for providing an answer to the commonly asked query, ‘Is there anything I can do to decrease my risk of melanoma recurrence?'”

This post hoc analysis included data from two randomized trials — the multinational first and second Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT-II).

Median follow-up was 110 months for MSLT-I and 67.6 months for MSLT-II. Patients with clinical stages I or II melanoma with a Breslow thickness of 1.00 mm or greater or Clark level IV to V, and available standard prognostic and smoking data, were included.

This analysis included 6,279 patients (mean age 52.7 years, 57.9% men), 17.2% of whom were current smokers, 27% former smokers, and 55.9% never smokers. Median follow-up was 78.4 months.

Jackson and colleagues found that current smoking was associated with male sex, younger age, trunk site, thicker tumors, tumor ulceration, and sentinel lymph node biopsy (SLNB) positivity.

When broken down by nodal groups, the increased risk of melanoma-specific mortality associated with current smoking was greatest for patients with SLNB-negative melanoma (HR 1.85, 95% CI 1.35-2.52, P<0.001) relative to never smokers.

However, an increased risk was also seen in patients with SLNB-positive melanoma (HR 1.29, 95% CI 1.04-1.59, P=0.02) and those who underwent nodal observation (HR 1.68, 95% CI 1.09-2.61, P=0.02).

The highest risk of all was in those patients with SLNB-negative disease who smoked 20 or more cigarettes a day, which more than doubled their risk of death due to melanoma (HR 2.06, 95% CI 1.36-3.13, P<0.001).

Jackson and colleagues emphasized that their analysis can’t prove a causal relationship between smoking tobacco and melanoma-associated death, pointing out that smoking-associated behaviors such as alcohol and marijuana use may also be contributing factors.

However, they noted that there are a number of potential mechanisms that promote tumor metastasis and worse survival in melanoma patients who smoke, which along with the appearance of a dose-response trend among current smokers in this study, “implicate smoking as a cause for diminished survival of melanoma.”

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