- Purpose of This PDQ Summary
- Smoking as a Primary Risk Factor
- Poorer Treatment Response in Cancer Patients
- Smoking as a Risk for Second Malignancy
- Effects of a Cancer Diagnosis on Quitting Smoking and Remaining Abstinent
- Smoking Intervention With Cancer Patients
- Pharmacological Treatment
- Current Clinical Trials
- Get More Information From NCI
- Changes to This Summary (10 / 22 / 2009)
- Questions or Comments About This Summary
- More Information
Smoking Cessation and Continued Risk in Cancer Patients (PDQ®): Supportive care - Health Professional Information [NCI]
This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER
Smoking Cessation and Continued Risk in Cancer Patients
Purpose of This PDQ Summary
This PDQ cancer information summary provides comprehensive, peer-reviewed information for health professionals about the risks of continued smoking in cancer patients and about quitting patterns and cessation intervention in these patients. This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board.
Information about the following is included in this summary:
- The effect of smoking on recurrence or on diagnosis of a second primary cancer in cancer patients.
- Patterns of quitting and continued smoking in cancer patients.
- Smoking intervention for cancer patients.
This summary is intended as a resource to inform and assist clinicians and other health professionals who care for cancer patients during and after cancer treatment. It does not provide formal guidelines or recommendations for making health care decisions. Information in this summary should not be used as a basis for reimbursement determinations.
This summary is also available in a patient version, which is written in less technical language, and in Spanish.
This summary briefly covers smoking as a primary risk factor for cancer, but the main focus is on the effect of smoking on recurrence or on diagnosis of a second primary cancer; patterns of quitting and continued smoking in cancer patients; and recommendations for smoking intervention for cancer patients. This information will assist health professionals caring for patients during and after treatment. Substantial material on cancer prevention and smoking cessation in the general population is available elsewhere. Because virtually all the available evidence pertains to cigarettes rather than other forms of tobacco such as snuff or chewing tobacco, reference is made to smoking cigarettes rather than to tobacco use.
Smoking as a Primary Risk Factor
The relationship between tobacco use and cancers of the lung and head and neck has been established for almost 50 years. Of the estimated 53,000 cases of head and neck cancer diagnosed each year, 85% are associated with tobacco use. The relative attributable risk for morbidity from smoking for lung cancer is more than 90%; it is between 60% and 70% for other smoking-related cancers (larynx, oral cavity, esophagus, bladder, kidney, pancreas, and other urinary cancers). Evidence suggests that smoking before age 30 years is a strong risk for colorectal cancer, with the risk appearing after a very long induction period (>35 years) in both men  and women. Smokers may also be at increased risk of regional and metastatic disease at diagnosis. In one study, smoking worsened the course or outcome of acute myeloid leukemia, particularly in younger patients and those with unfavorable karyotypes. A study of renal cell carcinoma patients suggests that improvement in renal cell carcinoma risk following smoking cessation may be relatively linear but may take more than 20 years to reduce risk to that of a nonsmoker. Smoking contributes to cancer development by causing mutations in tumor suppressor genes and dominant oncogenes and by impairing mucociliary clearance in the lungs and decreasing immunologic response. (Refer to the PDQ summary on Lung Cancer Prevention for more information.)
Poorer Treatment Response in Cancer Patients
Evidence exists for substantial medical advantage to an individual quitting smoking once cancer is diagnosed. There is substantial evidence that continued smoking may reduce the effectiveness of treatment and increase the likelihood of a second cancer (refer to the Smoking as a Risk for Second Malignancy section of this summary for further information). Continued smoking may also worsen side effects of treatment, though the direct evidence for this is surprisingly limited because few studies have evaluated this issue. If one extrapolates, however, from the extensive evidence of the effects of smoking on cardiovascular disease, pulmonary functioning, immunosuppression, and wound healing due to vasoconstriction, as well as the fairly rapid reduction of some effects following smoking cessation, these results might also apply to cancer patients, particularly if surgical management or lung functioning is involved. More specifically, one study outlines a model of cardiopulmonary toxicities in response to various antineoplastic therapies that may be potentiated by tobacco use; for example, smokers treated with bleomycin or carmustine would evidence higher levels of pulmonary fibrosis and restrictive lung disease, and the anthracyclines would lead to higher risk of cardiomyopathy in smokers. In a study of advanced head and neck cancer patients receiving radiation therapy, patients who continued to smoke suffered mucositis for a longer time (23.4 weeks) than did either patients who quit at the time of radiation therapy and remained abstinent (13.6 weeks) or patients who remained abstinent for at least a month after treatment (18.3 weeks). Extended mucositis may be associated with permanent alteration in appearance. In one study, patients receiving induction chemotherapy for acute myeloid leukemia who continued to smoke were more likely to experience severe pulmonary infection (26% vs. 18%), although overall survival rates did not differ in adults older than 60 years. Following radiation therapy for laryngeal carcinoma, patients who continue to smoke may be less likely to regain satisfactory voice quality. Another area of reasonable concern for patients who continue to smoke is the rate of general complications following any type of surgery; it is documented that wound healing postsurgery is slowed in smokers because both nicotine and carbon monoxide cause vasoconstriction, inhibition of epithelization, and creation of a cellular hypoxia.[7,8] In one study of predictors of complications following resection in lung cancer patients, a history of smoking doubled the likelihood of complications, but smoking at time of admission for surgery did not. No detailed information is provided, however, regarding the time since smoking ceased.
One study found decreased response rates and survival rates in head and neck cancer patients who continued to smoke. Patients who continued to smoke had a significantly lower rate of complete response to radiation therapy (45% vs. 74%) and 2-year survival (39% vs. 66%). Recent quitters were more similar to long-term quitters than to continued smokers in survival likelihood at 18 months.
Another study also showed an effect on survival rates of continued smoking in head and neck cancer patients. Those who stopped smoking had double the chance of survival, irrespective of extent of disease at diagnosis; after 2 years, survival of quitters approached that of nonsmokers. Relative risk for recurrence was about double in quitters and quadrupled in those who continued to smoke, regardless of the amount they smoked. One study failed to find significant differences in prognosis in resected stage I non-small cell lung cancer patients dependent on smoking status; the recurrence and death rates in both former and current smokers did not differ but were double to triple those of newer smokers. These differences failed, however, to reach statistical significance because of the small number of newer smokers; in addition, the lack of differences between former versus current smokers is hard to interpret because no definitions are provided. One study found a consistent trend in small cell cancer patients: continued smokers had the poorest survival, followed by patients who quit at diagnosis, then by patients who had quit on average 2.5 years before diagnosis. Although survival curves of recent ex-smokers did not differ statistically from continued smokers, perhaps because of small numbers, no continued smokers (n = 57) survived past 131 weeks, whereas 6 of those who quit at diagnosis (n = 35) were in complete remission at 1 to 2 years. The relationship between smoking and progression of prostate cancer has also been examined. Another study found a much higher 5-year tumor-specific mortality rate among smokers with stage D2 disease (88% vs. 63%) or non–stage A disease (39% vs. 17%), which was attributed to the effects of continued smoking as an immunosuppressant. Yet another study found longer survival rates in prostate cancer patients who are nonsmokers, but this study did not examine the effects of quitting. Survival and recurrence data for lung cancer are mixed.
Smoking as a Risk for Second Malignancy
Persons who initially present with both smoking-related and non–smoking-related malignancy face increased risk of a second malignancy at the same site or another site if they continue to smoke.[1,2] When prognosis is more favorable for the initial cancer, the evidence is even stronger that continued smoking increases the risk of new primary cancers for up to 20 years after original diagnosis. In two studies of survivors of small cell lung cancer (SCLC) (mostly stage I and II),[3,4,5] risk of a second cancer (mostly non-SCLC [NSCLC]) was 3.5-fold to 4.4-fold higher than in the general population. In those who continued to smoke, the risk was far higher, particularly in those who also received chest irradiation (relative risk [RR] = 21.0) and alkylating agents (RR = 19.0). In individuals who stopped smoking at the time of diagnosis, the risk was no higher than in those who had stopped smoking at least 6 months before diagnosis. In a study of breast cancer survivors who subsequently developed lung cancer, the risk for subsequent lung cancer in those who were treated with thoracic radiation therapy (XRT) alone was negligible, whereas the risk attributable to smoking was substantial (adjusted odds ratio [OR] = 5.6) and even higher for a combination of XRT and smoking (unadjusted OR = 9.0, P < .05; adjusted OR = 8.6, P = .08). Even higher multiplicative risk for subsequent lung cancer from radiation treatment and smoking (RR = 20.2) was identified in a study of Hodgkin disease survivors. This study  found higher multiplicative effects (RR = 49.1) for a combination of radiation and alkylating agents in moderate-to-heavy smokers compared with comparison cases. Another study in Japan confirmed that patients with SCLC who survive at least 2 years greatly reduced their likelihood of a second cancer if they quit smoking.
Patients with oral and pharyngeal cancers who smoke also have an exceptionally high rate of second primary cancers. A follow-up study of more than 1,000 patients with oral cancers found that the risk of a second cancer increased with continued smoking up to almost five times as much (OR = 4.7) for all aerodigestive cancers among long-term heavy smokers (two packs or more per day), even after controlling for alcohol, which carries its own excess risk. No effect was seen for quitting within 2 years, but risk decreased significantly after 5 years' cessation. Another study  confirmed this increased risk, though at a somewhat lower level. More than 1,000 patients with early-stage head and neck squamous cell carcinoma were examined for the joint effects of tobacco and alcohol exposure on second primary tumors (SPT) up to 6 years after initial diagnosis. SPT cases were more likely to be current smokers (27.5% vs. 18.8%) who smoked more for a longer period and used forms of tobacco other than cigarettes or in combination with cigarettes. Overall risk for SPT was approximately double for smokers. Most increased risk was associated with continued smoking (RR = 2.1) and alcohol intake (RR = 1.3) after diagnosis, though no interaction effect was evident.
The relationship between smoking and progression of prostate cancer has also been documented. One study found a much higher 5-year tumor-specific mortality rate among smokers with stage D2 disease (88% vs. 63%) or non–stage A disease (39% vs. 17%), which was attributed to immunosuppressive effects of continued smoking. Finally, the impact of smoking on risk of a secondary lung cancer has been demonstrated in survivors of Hodgkin lymphoma.[12,7]
Effects of a Cancer Diagnosis on Quitting Smoking and Remaining Abstinent
Most patients with a smoking-related cancer stop smoking or make serious efforts to quit at the time of diagnosis.[1,2,3,4] One study reported that approximately half of a group of patients with oral and pharyngeal cancers quit at or after diagnosis; heavier smokers were substantially more likely to quit. Another study found a 12-month abstinence rate of 64.6% among head and neck cancer patients. A quit rate of 52% was reported in 115 head and neck cancer patients just before diagnosis, suggesting that an increase in smoking and cancer-related symptoms drives a substantial part of the decision to quit smoking, in addition to knowledge of the diagnosis. Even patients who continue to smoke may remain motivated to quit. In a group of stage I small cell lung cancer patients, almost 90% had made one or more attempts to quit smoking, though 60% of survivors still smoked at 2 years. In another study, 84% of the sample had made at least one attempt to quit since surgery, and 69% had made multiple attempts. These studies found that while 80% of larynx and pharynx cancer patients remained abstinent after surgery, only 20% of those with oral cavity cancers did so. Patients who had undergone less intensive treatment (in particular, radiation therapy) were more likely to remain smokers; if they quit, they were 2.46 times more likely to resume tobacco use, even after controlling for severity. Higher relapse rates have also been associated with less radical treatment of head and neck cancers. Such a relationship between continued smoking and less severe disease has also been found in cardiac patients. Another group in which secondary prevention may be particularly important is survivors of childhood cancer. In pediatric cancer survivors, initiation of smoking may be as high as in a group of healthy peers. An excellent review of the findings and recommendations in addressing smoking in this population has been published.
Smoking Intervention With Cancer Patients
Surprisingly few smoking intervention studies with cancer patients have been conducted. One study found that when consistent intervention was provided to a group of head and neck cancer patients, about 65% were able to quit and remain abstinent, including about half of those who expressed little interest in quitting at baseline. A large intervention study with head and neck cancer patients used surgeon- or dentist-delivered advice to stop smoking, contracted quit dates, written materials, and booster advice sessions. Partially because of a high drop-out rate, a significant intervention effect was not detected, though differences were in the expected direction. A similar study  also failed to find beneficial effects for very brief (<5 minutes) physician-delivered interventions based on the Ask, Advise, Assist, Arrange model outlined below. More than 400 cancer patients with a range of diagnoses were randomly assigned to receive either intervention or usual care. Approximately half had been diagnosed within the previous 6 months, 46.3% had tried to quit in the previous 6 months, and 84% were considering quitting in the following 6 months. Patients randomly assigned to the intervention group acknowledged receiving advice and resources from their physician consistent with the protocol; however, there were no significant differences in quit rates at either 6-month follow-up (11.9% vs. 14.4%) or 12-month follow-up (13.6% vs. 13.3%). Patients were more likely to quit smoking if they had been diagnosed with head and neck cancer or lung cancer, were lighter smokers, expressed a strong desire to quit, and used additional intervention resources. These results suggest that very brief physician counseling for this high-risk group is not adequate to improve quit rates.
A case-controlled retrospective study  examined the effects of referral to a nicotine dependence center for more than 200 smokers diagnosed with lung cancer compared with smokers without a lung cancer diagnosis. Most lung cancer patients were less likely to have made previous attempts to quit but expressed higher motivation to quit smoking than did individuals without lung cancer. Although the likelihood of being abstinent at 6 months postintervention was higher among lung cancer patients (22% vs. 14%), after adjusting for demographic variables and level of motivation, there was no statistically significant difference. Patients who were closer to diagnosis at the time of intervention were far more likely to be abstinent at 6 months (27.3% vs. 0% for 3–6 months vs. 7% for >6 months, P = .01). In general, a brief smoking intervention consisting of approximately 1 hour of tailored intervention, including prescription of pharmacologic treatment, showed relatively little impact in this high-risk population. However, referral sooner after diagnosis may increase the likelihood of quitting. This study is limited by the self-selection of patients and lack of a nonintervention comparison group.
Considerable work has been done, however, with other patient groups—particularly cardiac patients—establishing the valuable role of physicians and other health care providers in providing smoking intervention in the context of medical care. Specific recommendations for intervening in tobacco use have been published in several contexts. On the basis of outcomes from six major clinical trials of physician-delivered smoking intervention conducted in the late 1980s, the Ask, Advise, Assist, Arrange model was developed. In this model, the physician provides a brief intervention that entails asking about smoking status at every visit, advising abstinence, assisting by setting a quit date, providing self-help materials and recommending use of nicotine replacement therapy, and arranging for a follow-up visit. See the list below for brief and expanded intervention outlines. The Patient-Centered Counseling Key Elements list below provides detailed questions that may be asked in the assist phase in a patient-centered counseling format that is brief enough (5–7 minutes) to be delivered within the context of a usual office visit.
These recommendations form the core of the Public Health Service–sponsored Clinical Practice Guideline [6,7] that extended the recommendations by strongly supporting the value of referral to more intensive counseling. Furthermore, in addition to the documented value of nicotine replacement therapy (using gum, lozenge, patch, nasal spray, or inhaler), there is now clear evidence for the value of the antidepressant bupropion HCl (Wellbutrin SR and Zyban), 150 mg twice a day, as an adjunct for treatment; however, these adjunctive pharmacological treatments have not been tested in cancer patients. Individuals should be advised to check with their physicians.
Not all smokers are equally motivated to stop smoking. One of the most useful models for physicians in understanding the motivational issues in stopping smoking and actually quitting is the Stages of Change Model. Most individuals attempting to change a complex behavior such as smoking go through several predictable stages, from precontemplation to contemplation to preparation and finally action. One of the goals of brief physician counseling is to move patients along these stages, until they are more motivated to quit. In addition, especially for first-time quitters, relapsing and cycling through these stages one or more times is common, until the person develops better behavioral skills. The most common triggers for relapse are stressful situations and social triggers for smoking. One study found that the patterns of relapse in head and neck cancer patients were comparable to patterns of relapse in quitters in the general population. Smokers should be encouraged to anticipate such situations and develop strategies for handling them, as part of developing a new identity as a nonsmoker. It may take more than a year for even motivated smokers to successfully make these changes. The Stages of Change Model is well described and summarized  and is outlined as part of the Ask, Advise, Assist, Arrange Key Elements list below. Other important information such as smoking history (e.g., amount smoked or previous attempts to quit) can be efficiently collected by asking patients to complete a brief set of self-assessment forms in the waiting room. Nicotine addiction can be assessed using the Fagerstrom Test for Nicotine Addiction, and behavioral patterns (e.g., tendency to smoke when under stress) can be assessed using the online Quit Guide.
Tailoring intervention for specific populations may also be important, although this has not been examined specifically in cancer patients. A study of the effects of self-help intervention materials designed for an African American population showed higher quit rates (25%) among those receiving the tailored materials than among those receiving the standard materials (15.4%) at 12 months postintervention.
Other investigators have begun to examine intervention approaches specific to patients at high risk for developing lung cancer, through the use of genetic biomarker feedback (presence of the CYP2D6 genetic abnormality, which increases the risk of developing lung cancer twofold to fourfold) in otherwise healthy smokers. Adding information on genetic risk for cancer to the usual counseling approaches increased initial quit rates significantly, but this effect was not maintained; such an approach may be a useful motivational component to add to a more comprehensive intervention but may not be sufficient in itself.
Ask, Advise, Assist, Arrange Key Elements
|4.||Arrange follow-up support:
Patient-Centered Counseling Key Elements
|3.||Resources for coping with problems
The following information is based on the successful use of pharmacological agents in the cessation of smoking in the general population. None of the following agents have been studied in large placebo-controlled studies in cancer patients for aid in smoking cessation. Dosage adjustments or titrations may be required when administering these agents to oncology patients.
Also used as an antidepressant, bupropion hydrochloride (HCl) (Zyban) is a nonnicotine aid to smoking cessation. It is a relatively weak inhibitor of the neuronal uptake of norepinephrine, serotonin, and dopamine and does not inhibit monoamine oxidase. The exact mechanism by which bupropion HCl enhances the ability of patients to abstain from smoking is unknown; however, it is presumed that this action is mediated by noradrenergic or dopaminergic mechanisms. One study  failed to find any additional value of bupropion HCl in reducing relapse in individuals using the nicotine patch compared with a placebo either as part of a relapse prevention program (after the end of successful patch therapy) or as a second-level treatment for individuals who were still smoking after nicotine-patch therapy.
|Rx||Zyban||150 mg/day × 3 days then increase to 300 mg/day × 7–12 weeks||Insomnia, dry mouth, dizziness, rhinitis||Do not take with Wellbutrin or Wellbutrin SR.|
|Higher incidence of seizures in patients treated for bulimia or anorexia.|
|Do not prescribe >300 mg/day for patients being treated for bulimia.|
Although bupropion HCl (Zyban) is the only U.S. Food and Drug Administration (FDA)-approved antidepressant for smoking cessation, fluoxetine HCl (Prozac) has recently been studied and shown to be effective.
|Rx||Prozac||30–60 mg/day||Insomnia, dizziness, anorexia, sexual dysfunction, confusion||Limited data available on its use in combination with cognitive-behavioral therapy.|
These products are designed to aid in the withdrawal symptoms associated with nicotine. Several precautions must be considered before initiating therapy, but these precautions do not constitute absolute contraindications.
- Patients who are pregnant or nursing should obtain advice from a health care professional before using these products.
- Patients should be advised to not use these products if they continue to smoke, chew tobacco, use snuff, or use other nicotine-containing products.
- Patients should be instructed to consult a physician before using these products if they are younger than 18 years, have heart disease or an irregular heartbeat, have high blood pressure not controlled by medication, have a history of or currently have esophagitis or peptic-ulcer disease, use insulin for diabetes, or take prescription medications for depression or asthma.
|Rx||Nicotrol NS||Max 40 mg/day||Local irritation||Max use 3 months.|
|Rx||Nicotrol Inhaler||Individualized||Local irritation||Use up to 24 weeks.|
Nicotine Polacrilex Gums
|OTC||Nicorette||18–24 mg/day||Sore throat, stomatitis||Max 30 pieces/day; decrease 1 piece every 4–7 days.|
|OTC||Nicorette DS||36–48 mg/day||Jaw ache||Max 20 pieces/day; decrease 1 piece every 4–7 days.|
|OTC||Commit||40–80 mg/day||Local irritation (warmth and tingling)||Use for 12 weeks; max 20 pieces/day. Weeks 1–6: 1–2 lozenges every 1–2 hours; weeks 7–9: 1 lozenge every 2–4 hours; weeks 10–12: 1 lozenge every 4–8 hours.|
|Rx||Habitrol||7–21 mg/day||Erythema||Use for 6–12 weeks.|
|OTC||Nicoderm CQ||7–21 mg/day||Pruritus||Use for 6–12 weeks.|
|OTC||Nicotrol||5–15 mg/day||Burning at site||Use for 14–20 weeks.|
|Rx||ProStep||11–22 mg/day||Local irritation||Use for 6–12 weeks.|
Lobeline (Bantron) is classified as a category III agent by the FDA (safe but no proven effectiveness). This product is not recommended for use in any smoking cessation program because of its lack of efficacy.
- Continued smoking substantially increases the likelihood of recurrence or occurrence of a second cancer in survivors, particularly in those who received radiation therapy.
- Most patients with smoking-related cancer appear motivated to quit smoking at the time of diagnosis.
- A stepped-care approach is recommended, with strong physician advice and brief counseling to quit and provision of basic information to all patients at each contact during the first month of diagnosis, followed by more intensive treatment (pharmacologic and counseling by a smoking specialist) for those having difficulty quitting or remaining abstinent.
Current Clinical Trials
Check NCI's PDQ Cancer Clinical Trials Registry for U.S. supportive and palliative care trials about smoking cessation intervention that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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Changes to This Summary (10 / 22 / 2009)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
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ADDITIONAL PDQ SUMMARIES
- PDQ® Cancer Information Summaries: Adult Treatment
Treatment options for adult cancers.
- PDQ® Cancer Information Summaries: Pediatric Treatment
Treatment options for childhood cancers.
- PDQ® Cancer Information Summaries: Supportive and Palliative Care
Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.
- PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer)
Tests or procedures that detect specific types of cancer.
- PDQ® Cancer Information Summaries: Prevention
Risk factors and methods to increase chances of preventing specific types of cancer.
- PDQ® Cancer Information Summaries: Genetics
Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.
- PDQ® Cancer Information Summaries: Complementary and Alternative Medicine
Information about complementary and alternative forms of treatment for patients with cancer.
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
Date Last Modified: 2009-10-22