Despite data showing that cigarette smoking is the number one risk factor for the development of lung cancer,1 and a leading cause of preventable disease, disability, and death in the United States, an estimated 30.8 million American adults continue to smoke cigarettes.2 Globally, the number of smokers has increased to an astounding 1.1 billion, resulting in nearly 8 million excess tobaccco--related deaths—480,000 deaths each year in the United States alone related to illness caused by tobacco use or exposure to second-hand smoke.3 Smoking is so addictive that about 30% of survivors continue to smoke even after a lung cancer diagnosis.4
Saverio Caini, MD, PhD
Vieri Scotti, MD
In addition to decreasing survival, smoking after a lung cancer diagnosis can result in increased treatment toxicity, higher risk of treatment failure, greater incidence of secondary primary tumors, and reduced quality of life.5 According to the results from a recent study investigating whether quitting smoking after a lung cancer diagnosis confers a beneficial effect on survival, smoking cessation was associated with a nearly 30% improvement in overall survival.6
The study was conducted by Saverio Caini, MD, PhD, Senior Medical Epidemiologist at the Institute for Cancer Research, Prevention, and Clinical Network, Florence, Italy, and Vieri Scotti, MD, Consultant Clinical Oncologist, Department of Oncology, Radiation Therapy Unit at Careggi University Hospital, Florence, and colleagues; they examined data presented in 21 articles published in MEDLINE and Embase between 1980 and 2021. The articles included information on more than 10,000 patients diagnosed with non–small cell lung cancer, small cell lung cancer, or lung cancer of an unspecified histologic subtype, and the impact on survival after quitting smoking at or around diagnosis or during treatment.
Quantifying the Risks of Smoking on Lung Cancer
According to the study authors, tobacco smoking promotes tumor growth, progression, and dissemination; decreases the efficacy of and tolerance to radiation and systemic therapies; and increases the risk of postoperative complications and secondary primary cancers, although the underlying biological mechanisms causing these potential effects are unknown. One possible explanation for why quitting smoking after a lung cancer diagnosis may offer a survival benefit is data suggesting epigenetic changes induced by tobacco smoking and its cessation may impact DNA methylation levels in patients with lung cancer. For example, there are data from some studies showing that low methylation levels in patients with lung adenocarcinoma conferred a survival benefit.7 However, this is just a hypothesis about one of the potentially many mechanisms at work, and there remains a lot that is unknown about why quitting smoking improves survival, according to Dr. Caini.
“The main result from our meta-analysis showing a nearly 30% survival benefit was derived from a ridiculously small number of studies,” said Dr. Caini. “There should be more research in this area.”
In this interview with The ASCO Post, Dr. Caini and Dr. Scotti talk about the results from their study; why it is never too late to reap the health benefits of smoking cessation; and how oncologists can help their patients to stop smoking.
Advocating for More Research
Did all patients in your meta-analysis, regardless of cancer stage, benefit from smoking cessation? What surprised you about your findings?
Dr. Caini: Unfortunately, we do not have an answer to that question because as you point out, our paper is a meta-analysis of published research on smoking cessation after a lung cancer diagnosis. We were quite surprised to find so few papers, only 21, on this topic, and the reported results could not be stratified by cancer stage because of a lack of information.
“We would love to know more about why some patients experienced a survival benefit [from smoking cessation after a lung cancer diagnosis] and others did not.”— Saverio Caini, MD, PhD
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On the one side, it is quite unbelievable that there is so little information on such an important prognostic factor as smoking cessation. We advocate for more studies with greater detail on this topic, including its interaction with tumor stage at diagnosis.
You analyzed data on 10,000 patients included in the 21 studies. Were they all current smokers, and did gender or race/ethnicity make a difference in which patients experienced a survival benefit from smoking cessation?
Dr. Caini: Yes, the patients were all current smokers. In terms of demographics, we did find some differences in survival based on age and sex, but they were insignificant. However, that may be because only a few of the study results were stratified by age and sex, so, again, we would love to know more about why some patients experienced a survival benefit and others did not. We ran some analyses to see whether the variability of results across the studies could be explained by demographics, but the number of studies, again, was just too small to conduct that type of analysis.
Reducing Treatment Complications
Why is smoking session after a lung cancer diagnosis so important to survival? Is it because no further lung damage is taking place, and these patients have a better response to treatment compared with patients who continue to smoke?
Dr. Caini: That is an important question. Of course, when you quit smoking, there are many health benefits that extend to many diseases in addition to lung cancer, including heart disease.
We analyzed overall survival in the patients in these studies, and it appears the survival benefit from smoking cessation was mainly from the risk of dying of lung cancer. However, why that is true is difficult to say. There is evidence showing that some treatments are more effective and have fewer adverse events in nonsmokers. There is also some evidence showing that smoking cessation may influence reducing tumor dissemination and progression.
Jennifer A. Ligibel, MD
Dr. Ligibel is Director of the Leonard P. Zakim Center for Integrative Therapies at Dana-Farber Cancer Institute. She is also Chair of ASCO’s Energy Balance Working Group and a member of ASCO’s Cancer Survivorship and Cancer Prevention Committees.
Each Prevention in Oncology column will address one of five areas in cancer prevention—alcohol use, obesity, tobacco use, vaccines to prevent cancer-causing infections, and germline genetics—with the goal of providing strategies to reduce the risk of cancer, as well as preventing cancer recurrence and second malignancy during cancer survivorship.
Dr. Scotti: I would just like to add an explanation from the clinical point of view. The results from surgical studies show that most patients have better overall survival when they stop smoking because they have fewer complications after surgery. On the contrary, for smokers with advanced disease, we now have some evidence that immunotherapy is most effective. However, further studies are needed to address this segment of patients and investigate the role of smoking cessation in patients who are candidates for immunotherapy. Until then, we are learning about the positive effects on survival with immunotherapy even after surgery in patients who smoke.
Educating Patients on the Risks of Smoking After Diagnosis
Studies show that many lung cancer survivors continue to smoke after their diagnosis. Please talk about the health risks in continuing to smoke after a lung cancer diagnosis, and how oncologists can help educate their patients about the benefits of not smoking?
Dr. Caini: Unfortunately, for most patients with advanced lung cancer, the prognosis is not good. We must make patients and physicians more aware of the risks involved when patients do not quit smoking. We also need to communicate that message better to patients. Our study suggests that physicians should educate patients with lung cancer about the benefits of smoking cessation, even after a diagnosis, and provide them with the necessary smoking cessation support.
Dr. Scotti: From the clinical point of view, it is important for physicians to keep in mind how critical smoking cessation is for patients. Surgeons are very convinced this is true. We must do more to make oncologists aware of this issue.
“We advocate that smoking cessation activities be integrated with the management of patients with cancer. It is even more important for smoking cessation programs to be integrated with lung cancer screening guidelines.”— Vieri Scotti, MD
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In Italy, we have very good smoking cessation programs for patients with lung cancer and for the general population. Many of these programs are tied to lung cancer screening programs.
We also need to address how to help our patients with locally advanced lung cancer to stop smoking and conduct studies to observe their survival outcomes. When we have those data, we will be able to say to patients, you need to stop smoking because you will have a better survival outcome.
Dr. Caini: The key point is to have an intervention for patients that improves their chances of survival. Improving survival by 20% to 30% is huge. There are not many systemic therapies that convey such a benefit. This information must be communicated well by treating oncologists to patients. We also need to recommend smoking cessation to former and current smokers who undergo screening for lung cancer.
Dr. Scotti: There is a lot of research underway in the value of lung cancer screening. We know that not smoking when you do not have cancer is beneficial, and we now know that smoking cessation, even after a lung cancer diagnosis, is also beneficial. Most patients participating in lung cancer screenings are current or former heavy smokers, and some may have lung cancer.
We advocate that smoking cessation activities be integrated with the management of patients with cancer. It is even more important for smoking cessation programs to be integrated with lung cancer screening guidelines.
DISCLOSURE: Dr. Caini and Dr. Scotti reported no conflicts of interest.
1. Centers for Disease Control and Prevention: What are the risk factors for lung cancer? Available at www.cdc.gov/cancer/lung/basic_info/risk_factors.htm. Accessed July 15, 2022.
2. Centers for Disease Control and Prevention: Current cigarette smoking among adults in the United States. Available at https://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/index.htm. Accessed July 15, 2022.
3. Centers for Disease Control and Prevention: Tobacco-related mortality. Available at www.cdc.gov/tobacco/data_statistics/fact_sheets/health_effects/tobacco_related_mortality/index.htm. Accessed July 15, 2022.
4. Burris JL, Studts JL, DeRosa AP, et al: Systematic review of tobacco use after lung or head/neck cancer diagnosis: Results and recommendations for future research. Cancer Epidemiol Biomarkers Prev 24:1450-1461, 2015.
5. Jassem J: Tobacco smoking after diagnosis of cancer: Clinical aspects. Transl Lung Cancer Res 8(suppl 1):S50-S58, 2019.
6. Caini S, Del Riccio M, Vettori V, et al: Quitting smoking at or around diagnosis improves the overall survival of lung cancer patients: A systematic review and meta-analysis. J Thorac Oncol 17:623-636, 2022.
7. Zhang R, Lai L, Dong X, et al: SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: An epigenomic-smoking interaction analysis. Mol Oncol 13:1235-1248, 2019.