Smoking at the time of a patient’s diagnosis of melanoma is linked to increases in lymph node metastases and increased melanoma-specific mortality risk, according to recent findings.¹

These findings were the results of a recent study conducted to evaluate any link observed between smoking cigarettes and the health outcomes of individuals that have clinically node-negative cutaneous melanoma. This research was led by Katherine M. Jackson, MD, from the Saint John’s Cancer Institute department of surgical oncology.

The investigators acknowledged that prior data from another study had indicated sentinel lymph node biopsy (SLNB) positivity was higher in individuals who were known to smoke.² Other previous research also had highlighted a connection with smoking and ulcerated primary melanoma tumors.³

“In the present study, we report smoking-associated survival data in the completed MSLT-I and MSLT-II datasets,” Jackson and colleagues wrote. “To our knowledge, the present study is one of the largest examining the association of smoking with outcomes among patients with clinical stage I and II cutaneous melanoma.”

Background and Findings

In this cohort study, the investigators used a retrospective analysis of informatio that was drawn from the randomized, multinational trials known as the first and second Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT-II). Enrollment for the former took place between January 1994 - March 2002, while the latter’s enrollment spanned from December 2004 - March 2014.

The research team’s criteria for participant inclusion was being aged 18 to 75 years and having clinical stages I or II melanoma. Participants’ melanoma would have a Breslow thickness of 1.00 mm or more, or Clark level IV to V, in addition to available standard prognostic data and smoking information.

Between October 2022 - March 2023, the team conducted their analyses, recording smoking habits of subjects at a single time at trial enrollment. Through the use of surveys and interviews, the investigators would have subjects self-identify as current, former, or never smokers.

The study also looked into any correlations between smoking status and survival across 3 main cohorts: Group 1, or those who did not receive sentinel lymph node biopsy (SLNB) in MSLT-I; Group 2, or individuals from both MSLT-I and MSLT-II who had SLNB with negative findings (known as the SLNB-negative group); and Group 3, made up of subjects from MSLT-I and MSLT-II who had gotten SLNB with tumor-positive nodes (known as the SLNB-positive group).

The main outcomes which the investigators evaluated were the melanoma-specific survival rates of those categorized by current smokers, former smokers, and ‘never smokers’. They looked at the whole cohort and each subgroup, using nodal observation and evaluating the existence of SLNB-negative or SLNB-positive findings.

Overall, there were 6,279 subjects evaluated by the research team, with a mean age of 52.7 years and 57.9% being identified as male. Extremities were reported by the team to have been the most common tumor site among 43.7%, and the mean Breslow thickness was 2.44 mm.

Among the 3 subgroups of potential smoking types, there were 17.2% current, 27.0% former, and 55.9% never smokers in the study population. The team’s median follow-up time was 78.4 months.

Several notable findings were uncovered, including that being a current smoker was associated with trunk site tumors, being of the male gender, being younger, ulceration, thicker lesions, and SLNB positivity. The investigators noted that current smoking substantially raised subjects’ risk of melanoma-associated death (HR 1.48, 95% CI 1.26-1.75; P< .001).

Notably, the research team found that former smoking was not shown to have such an association. The team also reported that the risk of melanoma-specific death connected with current smoking was shown to be highest among SLNB-negative patients (HR 1.85, 95% CI 1.35-2.52; P< .001), though it continued to be significant for nodal observation patients (HR 1.68, 95% CI 1.09-2.61; P= .02) and for SLNB-positive subjects (HR 1.29, 95% CI 1.04-1.59; P= .02).

A minimum of 20 cigarettes per day was also shown by the team to have doubled smokers’ risk of melanoma-related death among those labeled as SLNB-negative participants (HR 2.06, 95% CI 1.36-3.13; P < .001).

“Quantitative smoking data should be included in melanoma databases, and inclusion of smoking as a stratification factor in clinical trials should be considered,” they wrote. “Although the association of continued smoking was not specifically addressed in this study, it seems prudent to recommend smoking cessation to patients with melanoma at the time of diagnosis.”

References

1. ^{Jackson KM, Jones PC, Fluke LM, et al. 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.}
2. ^{Jones MS, Jones PC, Stern SL, et al. The impact of smoking on sentinel node metastasis of primary cutaneous melanoma. Ann Surg Oncol. 2017;24(8):2089-2094. doi:10.1245/s10434-017-5775-9.}
3. ^{Jones MS, Jones PC, Stern SL, et al. The impact of smoking on sentinel node metastasis of primary cutaneous melanoma. Ann Surg Oncol. 2017;24(8):2089-2094. doi:10.1245/s10434-017-5775-9.}