Smoking Cessation Associated With Increased Survival Among Patients With Lung Cancer

Former and current smokers have increased mortality compared to never smokers who were diagnosed with non–small cell lung cancer (NSCLC), according to the results of a study published in JAMA Network Open. Compared to never smokers, former smokers and current smokers experienced 26% and 68% increased mortality, respectively, and both had shorter overall survival (OS) among patients with early-stage disease.

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Smoking cigarettes and/or tobacco is the most significant factor associated with NSCLC, which accounts for 85% of all lung cancer cases. The average 5-year survival rate of NSCLC is below the rates of other common cancers (22.9%), and it has the highest economic burden of all cancers.

Smoking can cause molecular changes that increase with smoking pack-years. Therefore, investigators suggest that smoking cessation, over a period, may be associated with lower levels of biomarkers, which demonstrates the benefits of quitting on risk of cancer growth, progression, and mortality, according to the study.

“Smoking activities may cause molecular changes, as recent evidence has revealed that smoking is associated with certain oncogenic driver mutations and tumor mutation burden (TMB), a metric quantifying the number of somatic mutations occurring within the cancer genome,” the study authors wrote. “For example, the number of mutations in genes that promote oncogenic activities increases with smoking pack-years, and smoking cessation can reduce TMB, thus lowering risks of cancer progression and mortality.”

Investigators evaluated the independent associations of years since smoking cessation, cigarettes per day, and smoking pack-years with OS following lung cancer diagnosis in a prospective long-term cohort of 5594 patients with NSCLC with an average age 65.6 years who were recruited in Boston, Massachusetts, between 1992 and 2022. Within the cohort, 795 (14.2%) patients have never smoked, 3308 (59.1%) were former smokers, and 1491 (26.7%) were current smokers.

According to 30 years of data, early smoking cessation was associated with lower mortality after lung cancer diagnosis. In addition, years between quitting and diagnosis were associated with mortality.

“Doubling the years of smoking cessation preceding a lung cancer diagnosis was significantly associated with improved OS,” the study authors wrote in the article.

The current study expands on prior research that links longevity outcomes to smoking cessation. It also supports past literature, which determined that never smokers have the highest risk of later stage diagnosis.

Never smokers also had a higher proportion of lung adenocarcinomas, a subtype of NSCLC, than former and current smokers. However, the 5-year survival rate following lung adenocarcinoma diagnosis was 16% among former smokers compared to 23% among never smokers.

Current smokers had a significantly higher number of smoking pack-years compared to former smokers at 57 and 44, respectively. Current smokers tended to have an earlier diagnosis than former and never smokers. Of patients who died during the 30 years of follow-up, 79.3% were current smokers, 66.8% were former smokers, and 59.6% were never smokers.

The study has several limitations noted by the authors. The cohort lacked racial diversity, there was not a control for lifestyle confounders—such as physical activity and other healthy lifestyle habits—there was no detailed treatment information, there is possible recall bias, and investigators did not differentiate by cause of death.

“Detailed smoking history collection should be incorporated into future epidemiological and clinical studies to improve lung cancer prognosis and treatment selection,” the study authors wrote.

Reference

Wang X, Romero-Gutierrez C, Kothari J, et al. Prediagnosis Smoking Cessation and Overall Survival Among Patients With Non–Small Cell Lung Cancer. May 5, 2023. Accessed on May 15, 2023. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2804556?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=050523