Tobacco dependence is the most consequential target to reduce the burden of lung cancer worldwide. Quitting after a cancer diagnosis can improve cancer prognosis, overall health, and quality of life. Several oncology professional organizations have issued guidelines stressing the importance of tobacco treatment for patients with cancer. Providing tobacco treatment in the context of lung cancer screening is another opportunity to further reduce death from lung cancer. In this review, the authors describe the current state of tobacco dependence treatment focusing on new paradigms and approaches and their particular relevance for persons at risk or on treatment for lung cancer.
Key points
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Achieving smoking abstinence in the lung cancer screening setting or after cancer diagnosis improves health outcomes.
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Clinicians should actively engage in efforts to minimize stigma associated with continued smoking, especially after the diagnosis of cancer.
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Proactive approaches to offering tobacco treatment to all smokers regardless of readiness to quit can increase smoking abstinence.
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Varenicline is more effective than placebo, bupropion, and nicotine patches in helping smokers achieve abstinence.
Introduction
Tobacco dependence accounts for 1 in 5 deaths and is the number 1 preventable cause of disease and death in the United States, including the cause of about ∼120,000 deaths from lung cancer per year and a contributor to more than 25% of all deaths from cancer. , The overall prevalence of smoking cigarettes has decreased in the United States, yet remains high among the lowest-income individuals, those with substance use disorders and mental health issues, communities of color, and the LGBTQ community. , These are the same groups for which tobacco dependence interventions are less available, and medical misinformation widespread. Compared with other ethnic groups, African American smokers have the highest lung cancer mortality but show the lowest levels of cumulative smoke exposure, an observation often termed the “smoking paradox.” Persons with mental illness are challenged due to poor engagement and agency within a complex medical system and stigma about their ability to comply with a treatment plan. When diagnosed with lung cancer, low socioeconomic status (SES) groups frequently show worse outcomes with treatment and are almost twice as likely to die from lung cancer reflecting both economic and infrastructural factors.
These data suggest that the risk of lung cancer among smokers, especially in these populations with high tobacco use, is early, durable, and potent. Tobacco dependence is the most accessible and consequential target to reduce the burden of lung cancer worldwide. Smoking cessation after a lung cancer diagnosis improves survival and quality of life (QOL) and outreach efforts to direct lung cancer screening (LCS) to smokers in highly tobacco-encumbered but less medically accessible groups would likely yield tremendous health benefits. It remains unclear, however, whether the widespread incorporation of LCS will reach full potential of improving outcomes for smokers or former smokers in low SES tobacco-burdened subpopulations, because these individuals are under-represented among participants undergoing LCS. From a tobacco dependence treatment perspective, the most cost-effective strategy to reduce lung cancer mortality is to reduce initiation of tobacco use, enable aggressive multimodality tobacco dependence treatment for all smokers, and implement an LCS protocol that is anchored on tobacco dependence treatment. The ability to customize this 3-pronged approach to increase uptake in select populations is challenging and should be a priority for all health care providers. In this review, we describe the current state of tobacco dependence treatment, focusing on new paradigms and approaches and their particular relevance for persons at risk for or on treatment of lung cancer.
Benefits to incorporating tobacco treatment into the lung cancer care continuum
In 2014, the Surgeon General’s report highlighted that continued smoking after a cancer diagnosis adversely affects health outcomes and overall survival, but quitting after a cancer diagnosis can improve prognosis, overall health, and QOL. Studies show that continuing to smoke cigarettes after a lung cancer diagnosis is associated with increased risk of recurrence, a second primary lung cancer, treatment-related complications, and worse survival among those with non-small cell lung cancer (NSCLC), including early-stage NSCLC, as well as those with small-cell lung cancer. Furthermore, patients with lung cancer who smoke report lower QOL scores than those who do not smoke. Clinical benefits of smoking cessation may differ by stage of lung cancer. Although a large single-center study showed smoking cessation after the diagnosis of NSCLC improves survival, a multivariate analysis incorporating stage of disease and previous surgery yielded a trend toward survival without statistical significance. A larger meta-analysis, by contrast, of smoking cessation after diagnosis with early-stage lung cancer showed improved outcomes partially attributable to reduced cancer progression. Several oncology professional organizations (the National Comprehensive Cancer Network and the American Society of Clinical Oncology) issued guidelines stressing the importance of smoking cessation and tobacco treatment of patients with cancer. ,
Providing tobacco treatment in the context of LCS is another opportunity to reduce death from lung cancer and all-cause mortality of individuals with a substantial history of tobacco use. The National Lung Screening Trial (NLST) and the NELSON trial both demonstrated a reduction in lung cancer mortality with low-dose computed tomography (LDCT) screening of people at high risk of lung cancer. , Furthermore, in the NLST, current smokers, those with less than a high school education, and African Americans had a higher risk of death. Current smokers who underwent annual LDCT and achieved smoking abstinence had the greatest mortality reduction. Several guidelines recommend, and the Centers for Medicare and Medicaid Services require, that clinicians offer tobacco treatment with LCS. , An estimated half of individuals undergoing LCS will be current smokers ; thus LCS presents an opportunity to combine 2 interventions known to reduce smoking-related morbidity and mortality. , The Society for Research on Nicotine and Tobacco and the American Thoracic Society , have prioritized identifying effective approaches to tobacco treatment in the context of LCS.
Barriers to tobacco treatment in the lung cancer care continuum
A systematic review found that 30% of patients with lung cancer continue to smoke cigarettes after a cancer diagnosis. Furthermore, among smokers undergoing LCS, quit rates are estimated to be only 11%, in part due to a lack of delivery of guideline-recommended tobacco treatment provided by screening programs. , It is critical to recognize and address how stigma, social factors associated with low SES populations, and clinician and system barriers contribute to critical gaps between recommended evidence-based tobacco treatment guidelines and actual delivery of tobacco cessation treatment in the lung cancer care continuum.
Stigma, Guilt, and Shame
Stigma, implicit bias, and nihilism are corrupting influences which reduce an active smoker’s interest in the pursuit of tobacco dependence treatment across the entire lung cancer care spectrum. In fact, the stigma associated with lung cancer differentiates LCS process from all other screening. Many smokers blame themselves and also accept the blame of others for their smoking-related cancer diagnosis or their elevated risk. Studies have identified that patients with lung cancer often feel stigmatized because lung cancer tends to be associated with previous smoking.
Among patients diagnosed with lung cancer, internalized stigma such as self-blame, guilt, and regret, has been associated with increased depressive symptoms, delays in medical help-seeking, and lower QOL. , These factors can lead to unnecessary delay in enrolling in screening programs and diagnosis, engagement in clinical trials, and reluctance to comply with tobacco dependence treatment. , Recognizing the importance of identifying lung cancer stigma, Ostroff and colleagues developed the Lung Cancer Stigma Inventory, a reliable and valid assessment of 3 facets of stigma in lung cancer care settings: internalized stigma (directing negative societal attitudes toward oneself), perceived stigma (negative appraisal and devaluation from others), and constrained disclosure (discomfort in sharing one’s lung cancer status with others).
Acceptance and Commitment Therapy for Lung Cancer Stigma, a patient-focused cognitive behavioral intervention to reduce the self-blame, guilt, and inhibited disclosure is currently being studied. An urgent need exists for development and testing of additional psychosocial interventions that target lung cancer stigma as well as educational materials for clinicians and the general public to address stigma and implicit bias toward smokers. These materials should include information on how common smoking was in the days when many of those eligible for screening started smoking, describe the aggressive media campaigns by the tobacco industry to white-wash the attendant health risks, and delineate how tobacco control policies, in an effort to reduce the social acceptability of smoking, denormalized smoking and stigmatized smokers through positioning smoking as an environmental health issue (secondhand smoke), legislating smoke-free public areas and workplaces, and portraying smoking as a personal choice ultimately leading to a horrible death. Clinicians should approach smokers with sensitivity when discussing smoking status and actively engage in efforts to minimize the stigma associated with continued smoking, especially after the diagnosis of cancer.
Low Socioeconomic Status Barriers
SES is strongly associated with smoking status, the most important risk factor for lung cancer. Smoking prevalence in low SES and other vulnerable populations such as those with mental health illness and substance use disorders has declined at negligible rates compared with the general population. Low SES remains a risk factor for lung cancer diagnosis and mortality even after adjustment for smoking behavior and area-level measures of SES are associated with lung cancer risk in current and shorter-term former smokers only in this population. Conversely, an increase in SES over time was related to a decrease in mortality from respiratory disease, but not from lung cancer. The lack of financial resources or the ability to make healthy financial choices directly undermine the goals of early detection of lung cancer. Patients with lung cancer who do not receive therapy are more likely to be older, not white, male, and unmarried, to have no insurance or public insurance other than Medicare, to live in a low SES neighborhood, to have been seen at a non-National Cancer Institute cancer center hospital or hospital serving lower SES patients, and to have larger tumors. Therefore, SES significantly mediates racial/ethnic cancer survival disparities for several cancers including lung cancer.
Studies demonstrate that patient navigators, laypersons from the community who guide patients through the health care system to connect them with services they may have difficulty accessing, are a promising approach to promote smoking cessation and reduce disparities in cancer screening, diagnosis, and treatment. Among smokers residing in public housing, a smoking cessation intervention delivered by peer health advocates trained in motivation interviewing, basic tobacco treatment skills, and patient navigation increased tobacco abstinence at 12 months. In the LCS setting, a patient navigation program implemented in community health centers increased LDCT screening among high-risk current smokers.
Financial incentives promotes tobacco treatment engagement and smoking cessation in low SES populations. A randomized trial of low income smokers in the primary care setting showed that patient navigation combined with financial incentives increased 12-month tobacco abstinence. Incentives for stopping smoking has not been tested among patients undergoing LCS. A clinical trial in the LCS setting is underway to test the effectiveness of 4 approaches to help patients stop smoking, including an approach that delivers payments for successfully quitting.
Clinician and System Barriers
Clinicians’ experiences and views on smoking cessation services and perceived organizational constraints in settings considered teachable moments (LCS programs and cancer diagnosis) influence change in smoking behavior. , In the LCS setting, studies suggest that smokers with a screen-detected pulmonary nodule are more likely to quit smoking than those with normal results, and that discussing a screen-detected nodule is an opportunity to initiate a conversation about the desire to quit smoking. , Yet research suggests that physicians often missed this opportunity, expressing concern about overwhelming patients by discussing smoking cessation during delivery of abnormal results. Similarly, in the cancer diagnosis context, clinicians avoid talking about smoking because of competing priorities and concerns of implying and/or exacerbating patients’ guilt of smoking, even though patients often expected some conversation on smoking cessation. Barriers include time constraints, lack of awareness about smoking cessation services, and perceptions of responsibility for talking about smoking cessation. Thus, despite improved survival in patients with cancer who quit cigarettes, , many opportunities to promote smoking cessation are missed. ,
Tobacco cessation treatment pathways for patients with cancer have been developed that outline individualized treatment plans. However, within the lung cancer care continuum, tobacco treatment needs to be a team effort. Whether patients are interacting with a provider in the LCS setting, pulmonologists during diagnosis, and/or medical, radiation, and surgical oncologists during treatment, the unique challenges including stigma and cancer-related distress should be addressed. Strategies should include providing clinical evidence on the adverse effects of smoking on treatment outcomes and informing patients about the benefits of stopping smoking on side effects, treatment outcomes, and reduction in likelihood of recurrence. In addition, system-level changes are needed to promote tobacco treatment across lung cancer care. Such changes include incorporating reminders into practice systems, allocating resources for the development of tobacco treatment programs embedded in the cancer care setting, and gaining competency in treating tobacco dependence either online ( https://www.cdc.gov/tobacco/campaign/tips/partners/health/index.html ) or by attending specialized training in tobacco treatment ( http://ctttp.org/accredited-programs/ ).
A recently recognized systemic barrier to tobacco treatment is the issue of structural stigma. The unintended effects of public policies and social norms aimed to reduce smoking can sometimes have adverse effects on health care access and availability of tobacco dependence treatment. For example, the recent United States Department of Housing and Urban Development policy to expand smoke-free public housing needs to be intimately tethered to reliable tobacco treatment services to avoid homelessness and destabilization of families. Clinicians need to be cognizant of the upstream social determinants of health that affect a smoker’s engagement with the health system and how stigmatization of smoking validates discrimination by potential employers (eg, employers absorb a higher net cost of more than $6000 per year when they hire a smoker rather than a nonsmoker, reinforcing a low SES status and reducing access to medical care). There has been a call for medical education to include training in “structural competency,” in which knowledge about diseases is combined with analysis of social systems so that the structural determinants of stigma and health can be addressed.
Guideline-recommended pharmacotherapy and counseling
Understanding Nicotine Addiction
Tobacco dependence is a chronic relapsing disease that is sustained by nicotine addiction. Exogenous nicotine acts on nicotinic acetylcholine receptors (nAChRs) to activate brain dopamine release resulting in the rewarding effects of smoking cigarettes. By engaging with nicotinic receptors in distinct locations (ventral tegmental area [VTA]), nicotine generates a powerful, but incorrect survival signal. In addition, nicotine promotes learned associations (eg, exposure to people, places, or things previously associated with smoking cigarettes) that become persistent over time, placing people at risk for lifelong relapse.
Opt-Out Approaches
Studies suggest that only about 30% of current smokers are ready to quit within the next 30 days. Proactive approaches to offering guideline-recommended tobacco treatment to all smokers regardless of readiness to quit and allowing patients to refuse treatment (“opt-out”) have been shown to have both a high acceptance rate and to increase smoking abstinence. Among participants who quit smoking cigarettes, almost half stated that during initial assessment they were not ready to stop smoking cigarettes, underscoring the importance of engaging all smokers with tobacco treatment, regardless of motivation to quit smoking.
Pharmacotherapy
Pharmacotherapy effectively reduces withdrawal symptoms, and the combination of medication with counseling is more effective than either intervention alone in promoting smoking abstinence. The 7 US Food and Drug Administration (FDA)-approved medications for tobacco treatment include: (1) 5 types of nicotine replacement therapy (NRT) (over the counter: nicotine lozenges, gum and patches; prescription only: nicotine inhalers and nasal spray); (2) bupropion; and (3) varenicline.
Nicotine replacement therapy
NRT, an agonist at the nicotinic cholinergic receptors, delivers nicotine safely and prevents withdrawal symptoms. NRT is a nonaddictive, safe alternative to smoking because there is a much slower release and absorption of nicotine into the blood compared with the immediate nicotine peaks produced by cigarettes. Combination therapy with a transdermal nicotine patch (which delivers continuous dosing to provide steady levels of nicotine with peak blood levels of nicotine at 2–4 hours) and the nasal spray, inhaler, gum, or lozenge (delivers “as-needed” dosing in response to acute cravings; blood levels of nicotine peak 5 to 10 minutes after taking the nasal spray or inhaler and 20 minutes after using the gum or lozenge) is more effective in promoting prolonged abstinence, with a risk ratio of 1.34 compared with use of any single product. The FDA recommends 12 weeks of treatment with NRT, although treatment specialists often extend duration based on patient factors such as cigarette cravings and confidence to remain quit ( Table 1 ). No harm was reported in a randomized clinical trial with extended NRT use.
| Nicotine transdermal patch | ||
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| Nicotine lozenge: blood levels of nicotine peak at 20 min | ||
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| Nicotine gum: blood levels of nicotine peak at 20 min | ||
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| Nicotine inhaler blood: levels of nicotine peak at 5–10 min | ||
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| Nicotine spray: blood levels of nicotine peak at 5–10 min | ||
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