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Randomized Controlled Trial
. 2024 Feb 5;7(2):e2354751.
doi: 10.1001/jamanetworkopen.2023.54751.

Smoking Status and Survival in Patients With Early-Stage Primary Cutaneous Melanoma

Katherine M Jackson  1 , Peter C Jones  1 , Laura M Fluke  1 , Trevan D Fischer  1 , John F Thompson  2 , Alistair J Cochran  3 , Stacey L Stern  4 , Mark B Faries  5 , Dave S B Hoon  4 , Leland J Foshag  1
Affiliations
Randomized Controlled Trial

Smoking Status and Survival in Patients With Early-Stage Primary Cutaneous Melanoma

Katherine M Jackson et al. JAMA Netw Open. .

Abstract

Importance: While smoking is associated with a decreased incidence of cutaneous melanoma, the association of smoking with melanoma progression and death is not well defined.

Objective: To determine the association of smoking with survival in patients with early-stage primary cutaneous melanoma.

Design, setting, and participants: This cohort study performed a post hoc analysis of data derived from the randomized, multinational first and second Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT-II). Participants were accrued for MSLT-I from January 20, 1994, to March 29, 2002; MSLT-II, from December 21, 2004, to March 31, 2014. Median follow-up was 110.0 (IQR, 53.4-120.0) months for MSLT-I and 67.6 (IQR, 25.8-110.2) months for MSLT-II. Patients aged 18 to 75 years 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. Analyses were performed from October 4, 2022, to March 31, 2023.

Exposure: Current, former, and never smoking.

Main outcomes and measures: Melanoma-specific survival of patients with current, former, and never smoking status was assessed for the entire cohort and for nodal observation and among subgroups with sentinel lymph node biopsy (SLNB)-negative and SLNB-positive findings.

Results: Of 6279 included patients, 3635 (57.9%) were men, and mean (SD) age was 52.7 (13.4) years. The most common tumor location was an extremity (2743 [43.7%]), and mean (SD) Breslow thickness was 2.44 (2.06) mm. Smoking status included 1077 (17.2%) current, 1694 (27.0%) former, and 3508 (55.9%) never. Median follow-up was 78.4 (IQR, 30.5-119.6) months. Current smoking was associated with male sex, younger age, trunk site, thicker tumors, tumor ulceration, and SLNB positivity. Current smoking was associated with a greater risk of melanoma-associated death by multivariable analysis for the entire study (hazard ratio [HR], 1.48 [95% CI, 1.26-1.75]; P < .001). Former smoking was not. 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 < .001), but also present for patients with SLNB-positive melanoma (HR, 1.29 [95% CI, 1.04-1.59]; P = .02) and nodal observation (HR, 1.68 [95% CI, 1.09-2.61]; P = .02). Smoking at least 20 cigarettes/d doubled the risk of death due to melanoma for patients with SLNB-negative disease (HR, 2.06 [95% CI, 1.36-3.13]; P < .001).

Conclusions and relevance: The findings of this cohort study suggest that patients with clinical stage I and II melanoma who smoked had a significantly increased risk of death due to melanoma. Smoking status should be assessed at time of melanoma diagnosis and may be considered a risk factor for disease progression.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Thompson reported receiving grants from the Australian National Health and Medical Research Council during the conduct of the study and advisory board participation honoraria from Bristol Myers Squibb Australia and MSD Australia, advisory board participation honoraria and travel support from GSK Australia and Provectus Biopharmaceuticals Inc, and conference support from Novartis AG outside the submitted work. Dr Faries reported receiving grant funding from the National Institutes of Health during the conduct of the study and advisory board participation honoraria from Bristol Myers Squibb, Merck & Co Inc, Regeneron Pharmaceuticals Inc, and Instil Bio outside the submitted work. Dr Foshag reported receiving grant funding from the John Wayne Cancer Institute during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Patient Randomization Schemes From the First and Second Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT-II)
SLNB indicates sentinel lymph node biopsy; WLE, wide local excision.
Figure 2.
Figure 2.. Melanoma-Specific Survival of Current, Former, and Never Smokers
A, Patients who did not undergo sentinel lymph node biopsy (SLNB) (n = 741); overall P = .06. B, Patients with tumor-negative SLNB (n = 3178); overall P < .001. C, Patients with tumor-positive SLNB (n = 2360); overall P < .001. HR indicates hazard ratio.
Figure 3.
Figure 3.. Adjusted Risk of Melanoma-Associated Death (MAD) in Current vs Never Smokers
A, Data are stratified by smoking volume; B, by smoking volume within nodal groups (tumor-negative sentinel lymph node biopsy [SLNB-negative], SLNB-positive, and SNL plus observation). HR indicates hazard ratio.
See this image and copyright information in PMC

Comment in

References

    1. Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA. Environmental and chemical carcinogenesis. Semin Cancer Biol. 2004;14(6):473-486. doi:10.1016/j.semcancer.2004.06.010 - DOI - PubMed
    1. Blakely T, Barendregt JJ, Foster RH, et al. . The association of active smoking with multiple cancers: national census-cancer registry cohorts with quantitative bias analysis. Cancer Causes Control. 2013;24(6):1243-1255. doi:10.1007/s10552-013-0204-2 - DOI - PubMed
    1. Kessides MC, Wheless L, Hoffman-Bolton J, Clipp S, Alani RM, Alberg AJ. Cigarette smoking and malignant melanoma: a case-control study. J Am Acad Dermatol. 2011;64(1):84-90. doi:10.1016/j.jaad.2010.01.041 - DOI - PMC - PubMed
    1. Gibson JAG, Dobbs TD, Griffiths R, et al. . The association of smoking and socioeconomic status on cutaneous melanoma: a population-based, data-linkage, case-control study. Br J Dermatol. 2020;182(5):1136-1147. doi:10.1111/bjd.18526 - DOI - PMC - PubMed
    1. DeLancey JO, Hannan LM, Gapstur SM, Thun MJ. Cigarette smoking and the risk of incident and fatal melanoma in a large prospective cohort study. Cancer Causes Control. 2011;22(6):937-942. doi:10.1007/s10552-011-9766-z - DOI - PubMed

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