As detailed in Sections 3.4 and 3.5, smoking causes at least 16 different types of cancer.
The 2014 Surgeon General’s report was the first in its series to review the associations between cigarette smoking and health outcomes in cancer patients and survivors. It concluded that smoking causes adverse health outcomes in people with cancer, while cessation improves their prognosis. Smoking increases all-cause mortality and cancer-specific mortality in cancer patients and survivors, and increases the risk of second primary cancers that are caused by cigarette smoking, including lung cancer. Smoking may increase the risk of cancer recurrence, resulting in a poorer response to treatment, and increased treatment-related toxicity.1
A 2018 review published by the World Health Organization identified some of the mechanisms by which smoking affects outcomes of cancer treatment.2 These mechanisms include increased cancer cell proliferation, cell migration and metastasis (development of secondary cancers), acceleration of systemic clearance of cancer therapies, increased complications associated with treatment, and an increased risk of co-morbidities related to tobacco.
3.15.4.1 Survival and mortality
The World Health Organization review reinforces the findings from the Surgeon General’s report regarding the effects of smoking on cancer treatment outcomes, including increased risk of all-cause mortality, cancer-specific mortality, recurrence, and reduced quality of life. Specifically, this included studies of patients with lung cancer, head and neck cancers, bladder cancer and breast cancer.2 Further studies have shown that the risk of mortality, including mortality from cancer, is lower for people who have quit compared to those actively smoking at diagnosis, for a wide range of cancers caused by smoking.3
Studies of numerous different types of cancer also show the effects of smoking at diagnosis and continued smoking on the risk of dying from cancer. A 2018 meta-analysis of patients with colorectal cancer found that those who currently or formerly smoked had lower overall survival compared with those who never smoked. In the same study, smoking cessation, compared to current smoking, was linked with an improvement in overall and colorectal cancer-specific survival.4 Women diagnosed with breast cancer had an increased risk of mortality if they smoked at diagnosis, and if they continued to smoke after diagnosis. But quitting after diagnosis reduced this excess risk.5 More information about the effects of smoking on the prognosis of other specific cancers can be found in Section 3.5.
3.15.4.2 Surgery for cancer
People who smoke are higher risk of poor outcomes and complications after surgery to remove cancer, such as prostate cancer, bladder cancer, oesophagus cancer, lung cancer, bowel cancer and brain cancer (see Sections 3.15.1.2 and 3.15.1.3).
3.15.4.3 Chemotherapy
Chemotherapy refers to drug treatments for cancer that are usually non-targeted. These drugs inhibit cell replication and damage DNA to kill cancer cells. But their non-specific nature usually means that many other cells in the body can be adversely affected. This leads to considerable side effects that may include reduced immunity, hair loss, nausea, vomiting, infertility, peripheral neuropathy (hand and foot pain) and others.
Smoking may increase the risk of a range of negative outcomes associated with chemotherapy, such as reduced effectiveness of the treatment, increased side effects, higher risk of the cancer progression and higher risk of mortality.6,7 There is increasing evidence that smoking diminishes the effects of chemotherapy for a number of different cancer types and chemotherapies. However, some chemotherapies, such as docetaxel, do not seem to be affected by smoking.8,9 Furthermore, there are studies showing lower toxicity of some chemotherapies for people who smoke, which may be consistent with lower amounts of the drug entering the bloodstream and reduced effectiveness of the treatment.8,10
Non-small cell lung cancers in people who smoke tend to develop with a high rate of DNA mutations, making the tumours more likely to develop resistance to chemotherapy drugs.11 Multiple studies have shown that people who don’t smoke or have never smoked gain more benefit from treatment with chemotherapy for non-small-cell lung cancer, urothelial cancer and bladder cancer.7 Chemotherapy for small cell lung cancer is also less effective in people who smoke.12 People receiving chemoradiation therapy (a combination of chemotherapy and radiotherapy) for head and neck cancer are more likely to have a better response to this treatment if they don’t currently smoke.7
People with bladder cancer treated with chemotherapy before surgery were more likely to have adverse reactions and cancer recurrence if they currently smoked.13 Another study has shown that people receiving this treatment who smoke are less likely to benefit from the chemotherapy.14
Chemotherapy drugs such as irinotecan may be less potent in people who smoke because less of the drug circulates in their blood, indicating a potential risk of treatment failure.10 Interestingly, there appears to be a lower risk of side effects for irinotecan, consistent with a diminished exposure to the drug.10 A meta-analysis has found a range of positive, neutral and negative effects on risks of adverse effects after chemotherapy for different cancers for people who smoke compared to non-smokers.15 These differences may have arisen due to differing effects of smoking on different chemotherapy drugs or other unknown mechanisms.
3.15.4.4 Radiotherapy
Radiotherapy (radiation therapy) is a cancer treatment that focusses beams of radiation onto a tumour or region of the body affected by cancer, to kill the cancer cells. Side effects from radiotherapy may include pain, nausea, vomiting, fluid retention, mouth sores and others.
A meta-analysis from 2020 showed that smoking was associated with increased risk of complications, such as skin reactions and reduced pulmonary function, for people with breast cancer having radiotherapy after surgery.16
A 2022 meta-analysis showed that smoking was associated with numerous poor outcomes after radiotherapy for a variety of cancers.15 There was an increased risk for people who smoked of cancer returning after treatment for non-small cell lung cancer, head and neck cancers and cervical cancer. People who smoked also had a lower disease-free survival (length of time surviving without any signs of the cancer) than non-smokers after radiotherapy plus chemotherapy, indicating that the treatment was less effective. Toxicity from radiotherapy was higher in people who smoke compared to non-smokers for prostate cancer, non-small cell lung cancer, oesophageal cancer and breast cancer. However, this does not appear to be the case for head and neck cancers.15
A systematic review of radiotherapy complications found that people who smoke have a higher risk than non-smokers of severe skin reactions, infections, fatigue, increased pain, poorer cognitive function, more speech disturbances, oral mucositis, second primary cancer, higher risk of cancer returning, higher risk of metastasis (cancer spreading) risk lower survival rates, and heart attack.17 Most of the reviewed studies examined results for lung cancers, head and neck cancers, prostate cancer and breast cancer.
A history of smoking was a strong risk factor for mortality after chemoradiotherapy for nasopharyngeal cancer (cancer in the top of the throat).18 People who smoked five years before treatment had a four-fold higher risk of death compared to non-smokers by five and ten years after treatment.18
Radiotherapy for people who smoke who are being treated for breast cancer is more likely to result in side effects such as pain, scar tissue and skin inflammation (radiodermatitis), even when the latest radiotherapy technologies are used, which should have reduced side effects compared to older technology.19,20
3.15.4.5 Immunotherapy
Immunotherapy (“biological” therapy) for cancer refers to a range of drugs that invoke the body’s own immune response to kill cancer cells. A common form of immunotherapy, known as checkpoint inhibitor mediation, reactivates immune responses that have been suppressed by cancer cells, triggering immune responses to kill the cancer cells. Checkpoint inhibitor immunotherapies are used to treat a number of cancers caused by tobacco use, such as lung cancer, head and neck cancer, cervical cancer and bowel cancer.21
Numerous studies and meta-analyses have found that checkpoint inhibitor drugs are more effective for people who smoke compared to non-smokers. Never-smokers with non-small cell lung cancer treated with the checkpoint inhibitor called pembrolizumab had higher risk of disease progression and death compared to those who smoke.22 People with metastatic urothelial cancer treated with pembrolizumab also had a lower risk of disease progression and mortality if they smoked compared to non-smokers.23
A meta-analysis of high-quality trials testing checkpoint inhibitors on many cancers found similar results. Non-smokers had no increase in survival with checkpoint inhibitor therapy above the benefit of chemotherapy for some cancers, however people who smoked benefitted more from immunotherapy than from chemotherapy.24 A similar meta-analysis also found that current or former smokers had an increase in progression-free survival and overall survival with checkpoint inhibitor immunotherapy compared to chemotherapy, irrespective of cancer type.25 But a greater benefit was not seen for people who smoke with renal cell carcinoma (a type of kidney cancer).26
It should be noted that a greater benefit of checkpoint inhibitor immunotherapy over chemotherapy for people who smoke does not necessarily mean that they have increased survival from these cancers overall, rather that—for people who smoke— checkpoint inhibitor therapy is a more effective treatment than chemotherapy in specific circumstances.
Numerous potential mechanisms are suggested for the greater response to checkpoint inhibitor therapy in people who smoke. These drugs appear to be better suited to killing the types of tumours that are caused by exposure to tobacco smoke. For instance, tumours caused by smoking often have relative higher amounts of DNA mutations and new forms of proteins found on the cell surface. These features may trigger more effective immune recognition of the cancer and activation of the immune responses that kill the cancer cell.24 There is also some evidence that smoking can increase the production of the proteins that suppress the immune system, meaning that when they are inhibited, this may affect the cancer cells in people who smoke more than in non-smokers.24
3.15.4.6 Other cancer treatments
Stem cell transplantation can be an effective treatment for some blood cancers. In a cohort study, smoking was found to be an independent risk factor for mortality within five years after stem cell transplantation.27 People with leukaemia who smoked at the time of transplantation had a higher risk of longer hospitalisation and mortality.28 Smoking was also a risk factor for dangerous fungal infections after stem cell transplantation.29
Carfilzomib is used to treat multiple myeloma, but patients may suffer from cardiovascular side effects. People who smoke have an almost 3-fold higher chance of experiencing cardiovascular side effects from this drug compared to non-smokers.30
Tyrosine kinase inhibitors (TKIs) are targeted (i.e. non-chemotherapy) medications that inhibit growth of cancer cells and improve prognosis for people with a variety of cancer types. TKIs may be used in combination with other drugs. Bevacizumab, which blocks new blood vessel formation and osimertinib, a TKI, are used together by people with non-small cell lung cancer that has spread. This drug combination is more effective for people who smoke compared to non-smokers.31 Some of the smoking-induced damage to DNA appears to makes these lung cancer cells more susceptible to these drugs, compared to the same cancer in people who do not smoke.31 However, a history of smoking is not always an advantage for people taking TKI drugs. An example is the drug imatinib, taken by people with chronic myeloid leukemia. Patients who smoke had an increased risk of treatment resistance to imatinib, where the tumours no longer respond to the drug.32 People who smoke with lung cancer that has spread also have a higher risk of mortality when treated with some specific TKIs.33
People with pancreatic cancer may benefit from a treatment called neoadjuvant FOLFIRINOX. FOLFIRINOX is a combination of four drugs used before surgery to shrink tumours. People with pancreatic cancer who receive this treatment survive for longer than those who have surgery without the drugs, but the benefit of the drug is reduced for people who smoke at the time of surgery, compared to former smokers or people who have never smoked.34
3.15.4.7 Side effects and quality of life
More severe pain has been associated with smoking in patients with cancer,35 and specifically for lung cancer36 and head and neck cancers.37 This may be because of the decreased effectiveness of opioids (due to increased drug metabolism caused by cigarette smoke components) described in Section 3.15.2, and failure of treating physicians to increase the dose to compensate.
The is some evidence that quality of life, and health-related quality of life, are lower for people who smoke after diagnosis with lung cancer.38,39 A systematic review that included over 10,000 people found a tendency for lower quality of life scores reported by people who smoke compared with non-smokers, after diagnosis with lung cancer.38 However, the authors clarified that quality of life is difficult to study for these people.38 One study has found that, for people with a variety of cancer types, smoking cessation is associated with improved quality of life over time.40
3.15.4.8 Second primary cancer
A second primary cancer refers to a new cancer diagnosis for people who have had cancer in the past. This is not the same as spreading (metastasis) of a cancer to different sites in the body. Some cancer therapies, such as radiotherapy, may increase the risk of a second primary tumour.
A meta-analysis has found that for people who have previously been diagnosed with one of a variety of different cancers, those with a history of smoking had an increased risk of second primary cancer. People who currently smoke had a 2.7-fold increased risk of a second primary cancer compared to never-smokers, and former smokers had a 1.4-fold increased risk.41
There is evidence that people who smoke have a higher risk of second primary cancer for lung cancer,42 cervical cancer,43 head and neck cancers44 prostate cancer45 and breast cancer.46
That smoking is the cause of many different types of cancer and is known to cause damage to the body that underlies cancer formation, are most likely the reasons that people who smoke would develop a second primary cancer. An Australian study has shown that people who smoke are more likely to get a smoking-related second primary cancer compared to other types of cancer.47
3.15.4.9 Effects of cessation
Smoking cessation is often associated with improved outcomes in cancer patients. Cessation is associated with an improved quality of life (in patients with lung or head and neck cancers), reduced risk of cancer-specific mortality (in patients with breast cancer) and improvement in survival (for patients with lung cancer, head and neck, colorectal and bladder cancer).48 People who stop smoking also experience reduced treatment-related toxicity,6,48,49 and are less likely to get a second primary cancer.50
The 2020 edition of the US Surgeon General’s report concluded that the evidence suggests smoking cessation may improve e all-cause mortality in cancer patients who smoked at the time of a cancer diagnosis.
For an overview of smoking cessation interventions for people with cancer, see Section 7.12.4.
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References
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50. Luo SJ, Choi E, Aredo JV, Wilkens LR, Tammemagi MC, et al. Smoking cessation after lung cancer diagnosis and the risk of second primary lung cancer: The multiethnic cohort study. JNCI Cancer Spectrum, 2021; 5(5). Available from: https://www.ncbi.nlm.nih.gov/pubmed/34611582