. 2023 Sep;8(9):e691-e700.

doi: 10.1016/S2468-2667(23)00131-7.

Association between duration of smoking abstinence before non-small-cell lung cancer diagnosis and survival: a retrospective, pooled analysis of cohort studies

Aline F Fares¹, Yao Li², Mei Jiang³, M Catherine Brown⁴, Andrew C L Lam⁴, Reenika Aggarwal⁴, Sabine Schmid⁵, Natasha B Leighl⁴, Frances A Shepherd⁴, Zhichao Wang⁶, Nancy Diao⁷, Angela S Wenzlaff⁸, Juntao Xie⁹, Takashi Kohno¹⁰, Neil E Caporaso¹¹, Curtis Harris¹², Hongxia Ma¹³, Matthew J Barnett¹⁴, Leticia Ferro Leal¹⁵, G Fernandez-Tardon¹⁶, Mónica Pérez-Ríos¹⁷, Michael P A Davies¹⁸, Fiona Taylor¹⁹, Ben Schöttker²⁰, Paul Brennan²¹, David Zaridze²², Ivana Holcatova²³, Jolanta Lissowska²⁴, Beata Świątkowska²⁵, Dana Mates²⁶, Milan Savic²⁷, Hermann Brenner²⁸, Angeline Andrew²⁹, Angela Cox³⁰, John K Field¹⁸, Alberto Ruano-Ravina³¹, Sanjay S Shete³², Adonina Tardon¹⁶, Ying Wang³³, Loic Le Marchand³⁴, Rui Manuel Reis³⁵, Matthew B Schabath³⁶, Chu Chen³⁷, Hongbing Shen¹³, Brid M Ryan¹², Maria Teresa Landi¹¹, Kouya Shiraishi³⁸, Jie Zhang⁹, Ann G Schwartz⁸, Ming S Tsao⁴, David C Christiani⁷, Ping Yang³⁹, Rayjean J Hung⁴⁰, Wei Xu⁴¹, Geoffrey Liu⁴²

Affiliations

¹ Princess Margaret Cancer Centre and University Health Network, University of Toronto, Toronto, ON, Canada; Division of Medical Oncology, Faculty of Medicine of São José do Rio Preto, São Paulo, Brazil.
² Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
³ Princess Margaret Cancer Centre and University Health Network, University of Toronto, Toronto, ON, Canada; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁴ Princess Margaret Cancer Centre and University Health Network, University of Toronto, Toronto, ON, Canada.
⁵ Princess Margaret Cancer Centre and University Health Network, University of Toronto, Toronto, ON, Canada; Universitätsklinik für Medizinische Onkologie, Inselspital Bern, Bern, Switzerland.
⁶ Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; Division of Pulmonary and Critical Care Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
⁷ Harvard T H Chan School of Public Health, Harvard University, Boston, MA, USA.
⁸ Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
⁹ Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
¹⁰ Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
¹¹ National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
¹² Laboratory of Human Carcinogenesis, Centre for Cancer Research, National Institutes of Health, Bethesda, MD, USA.
¹³ Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
¹⁴ Public Health Sciences, Biostatistics Program, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹⁵ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
¹⁶ University Institute of Oncology of Asturias-Cajastur Social Programme, University of Oviedo, Oviedo, Spain; Health Research Institute of Asturias, Oviedo, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública, Oviedo, Spain.
¹⁷ Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain.
¹⁸ Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
¹⁹ Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK; Weston Park Cancer Centre, Sheffield Teaching Hospital Foundation Trust, Sheffield, UK.
²⁰ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; Network of Aging Research, Heidelberg University, Heidelberg, Germany.
²¹ Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
²² N N Blokhin National Medical Research Centre of Oncology, Moscow, Russia.
²³ Institute of Public Health and Preventive Medicine and Department of Oncology, Second Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic.
²⁴ Department of Cancer Epidemiology and Prevention, M Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
²⁵ Nofer Institute of Occupational Medicine, Łódź, Poland.
²⁶ National Institute of Public Health, Bucharest, Romania.
²⁷ Department of Thoracic Surgery, Clinical Center of Serbia, Belgrade, Serbia.
²⁸ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center, Heidelberg, Germany; National Center for Tumor Diseases, German Cancer Research Center, Heidelberg, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany.
²⁹ Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
³⁰ Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
³¹ Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain; Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain.
³² M D Anderson Cancer Center, University of Texas, Houston, TX, USA.
³³ American Cancer Society, Atlanta, GA, USA.
³⁴ University of Hawai'i Cancer Centre, University of Hawai'i, Honolulu, HI, USA.
³⁵ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil; Life and Health Sciences Research Institute, Medical School, University of Minho, Braga, Portugal; Life and Health Sciences Research Institute-Biomaterials, Biodegradables and Biomimetics Research Group Associate Laboratory, Braga, Portugal.
³⁶ H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
³⁷ Program in Epidemiology, Cancer Prevention Program, Fred Hutchinson Cancer Center, Seattle, WA, USA.
³⁸ Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan; Department of Clinical Genomics, National Cancer Center Research Institute, Tokyo, Japan.
³⁹ Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
⁴⁰ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Lunenfeld-Tanenbaum Research Institute, Sinai Health Systems, Toronto, ON, Canada.
⁴¹ Princess Margaret Cancer Centre and University Health Network, University of Toronto, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. Electronic address: wei.xu@uhnres.utoronto.ca.
⁴² Princess Margaret Cancer Centre and University Health Network, University of Toronto, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.

PMID: 37633678
PMCID: PMC10540150
DOI: 10.1016/S2468-2667(23)00131-7

Association between duration of smoking abstinence before non-small-cell lung cancer diagnosis and survival: a retrospective, pooled analysis of cohort studies

Aline F Fares et al. Lancet Public Health. 2023 Sep.

. 2023 Sep;8(9):e691-e700.

doi: 10.1016/S2468-2667(23)00131-7.

Authors

Affiliations

¹ Princess Margaret Cancer Centre and University Health Network, University of Toronto, Toronto, ON, Canada; Division of Medical Oncology, Faculty of Medicine of São José do Rio Preto, São Paulo, Brazil.
² Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
³ Princess Margaret Cancer Centre and University Health Network, University of Toronto, Toronto, ON, Canada; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁴ Princess Margaret Cancer Centre and University Health Network, University of Toronto, Toronto, ON, Canada.
⁵ Princess Margaret Cancer Centre and University Health Network, University of Toronto, Toronto, ON, Canada; Universitätsklinik für Medizinische Onkologie, Inselspital Bern, Bern, Switzerland.
⁶ Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; Division of Pulmonary and Critical Care Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
⁷ Harvard T H Chan School of Public Health, Harvard University, Boston, MA, USA.
⁸ Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
⁹ Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
¹⁰ Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
¹¹ National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
¹² Laboratory of Human Carcinogenesis, Centre for Cancer Research, National Institutes of Health, Bethesda, MD, USA.
¹³ Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
¹⁴ Public Health Sciences, Biostatistics Program, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹⁵ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
¹⁶ University Institute of Oncology of Asturias-Cajastur Social Programme, University of Oviedo, Oviedo, Spain; Health Research Institute of Asturias, Oviedo, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública, Oviedo, Spain.
¹⁷ Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain.
¹⁸ Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
¹⁹ Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK; Weston Park Cancer Centre, Sheffield Teaching Hospital Foundation Trust, Sheffield, UK.
²⁰ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; Network of Aging Research, Heidelberg University, Heidelberg, Germany.
²¹ Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
²² N N Blokhin National Medical Research Centre of Oncology, Moscow, Russia.
²³ Institute of Public Health and Preventive Medicine and Department of Oncology, Second Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic.
²⁴ Department of Cancer Epidemiology and Prevention, M Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
²⁵ Nofer Institute of Occupational Medicine, Łódź, Poland.
²⁶ National Institute of Public Health, Bucharest, Romania.
²⁷ Department of Thoracic Surgery, Clinical Center of Serbia, Belgrade, Serbia.
²⁸ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center, Heidelberg, Germany; National Center for Tumor Diseases, German Cancer Research Center, Heidelberg, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany.
²⁹ Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
³⁰ Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
³¹ Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain; Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain.
³² M D Anderson Cancer Center, University of Texas, Houston, TX, USA.
³³ American Cancer Society, Atlanta, GA, USA.
³⁴ University of Hawai'i Cancer Centre, University of Hawai'i, Honolulu, HI, USA.
³⁵ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil; Life and Health Sciences Research Institute, Medical School, University of Minho, Braga, Portugal; Life and Health Sciences Research Institute-Biomaterials, Biodegradables and Biomimetics Research Group Associate Laboratory, Braga, Portugal.
³⁶ H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
³⁷ Program in Epidemiology, Cancer Prevention Program, Fred Hutchinson Cancer Center, Seattle, WA, USA.
³⁸ Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan; Department of Clinical Genomics, National Cancer Center Research Institute, Tokyo, Japan.
³⁹ Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
⁴⁰ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Lunenfeld-Tanenbaum Research Institute, Sinai Health Systems, Toronto, ON, Canada.
⁴¹ Princess Margaret Cancer Centre and University Health Network, University of Toronto, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. Electronic address: wei.xu@uhnres.utoronto.ca.
⁴² Princess Margaret Cancer Centre and University Health Network, University of Toronto, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.

PMID: 37633678
PMCID: PMC10540150
DOI: 10.1016/S2468-2667(23)00131-7

Abstract

Background: The association between duration of smoking abstinence before non-small-cell lung cancer (NSCLC) diagnosis and subsequent survival can influence public health messaging delivered in lung-cancer screening. We aimed to assess whether the duration of smoking abstinence before diagnosis of NSCLC is associated with improved survival.

Methods: In this retrospective, pooled analysis of cohort studies, we used 26 cohorts participating in Clinical Outcomes Studies of the International Lung Cancer Consortium (COS-ILCCO) at 23 hospitals. 16 (62%) were from North America, six (23%) were from Europe, three (12%) were from Asia, and one (4%) was from South America. Patients enrolled were diagnosed between June 1, 1983, and Dec 31, 2019. Eligible patients had smoking data before NSCLC diagnosis, epidemiological data at diagnosis (obtained largely from patient questionnaires), and clinical information (retrieved from medical records). Kaplan-Meier curves and multivariable Cox models (ie, adjusted hazard ratios [aHRs]) were generated with individual, harmonised patient data from the consortium database. We estimated overall survival for all causes, measured in years from diagnosis date until the date of the last follow-up or death due to any cause and NSCLC-specific survival.

Findings: Of 42 087 patients with NSCLC in the COS-ILCCO database, 21 893 (52·0%) of whom were male and 20 194 (48·0%) of whom were female, we excluded 4474 (10·6%) with missing data. Compared with current smokers (15 036 [40·0%] of 37 613), patients with 1-3 years of smoking abstinence before NSCLC diagnosis (2890 [7·7%]) had an overall survival aHR of 0·92 (95% CI 0·87-0·97), patients with 3-5 years of smoking abstinence (1114 [3·0%]) had an overall survival aHR of 0·90 (0·83-0·97), and patients with more than 5 years of smoking abstinence (10 841 [28·8%]) had an overall survival aHR of 0·90 (0·87-0·93). Improved NSCLC-specific survival was observed in 4301 (44%) of 9727 patients who had quit cigarette smoking and was significant at abstinence durations of more than 5 years (aHR 0·87, 95% CI 0·81-0·93). Results were consistent across age, sex, histology, and disease-stage distributions.

Interpretation: In this large, pooled analysis of cohort studies across Asia, Europe, North America, and South America, overall survival was improved in patients with NSCLC whose duration of smoking abstinence before diagnosis was as short as 1 year. These findings suggest that quitting smoking can improve overall survival, even if NSCLC is diagnosed at a later lung-cancer screening visit. These findings also support the implementation of public health smoking cessation strategies at any time.

Funding: The Alan B Brown Chair, The Posluns Family Fund, The Lusi Wong Fund, and the Princess Margaret Cancer Foundation.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests We declare no competing interests.

Figures

**Figure 1:. Overall survival curves among subgroups of patients with NSCLC by smoking status and by duration of smoking abstinence among people who have ever smoked**
(A) Unadjusted Kaplan-Meier curve by smoking status. (B) Unadjusted Kaplan-Meier curve among people who have ever smoked. (C) Fully adjusted survival curve by smoking status, estimated by Cox proportional-hazards model and adjusted by age, sex, ethnicity, educational status, clinical stage at diagnosis, study site, year of diagnosis, and histology. (D) Fully adjusted survival curve among people who have ever smoked, estimated by Cox proportional-hazards model and adjusted by age, sex, ethnicity, education, clinical stage at diagnosis, study site, year of diagnosis, histology, and pack years. Number at risk are provided for unadjusted survival curves. The p values of (A) and (B) are based on log-rank tests; the p-values of (C) and (D) are based on likelihood-ratio tests. NSCLC=non-small-cell lung cancer.

**Figure 2:. Association of long-term smoking abstinence (5–25 years) before a diagnosis of NSCLC with overall survival or NSCLC cancer-specific survival**
(A) Smoothed penalised spline curve showing hazard ratios of overall survival comparing former and current smokers. (B) Smoothed penalised spline curve showing hazard ratios of NSCLS-specific survival comparing former and current smokers. Former and current smokers are plotted against years of smoking abstinence. NSCLC=non-small-cell lung cancer.

Figure 3:. Forest plots of adjusted overall-survival HR and adjusted SHR for NSCLC-specific survival of former smokers with more than 1 year of smoking abstinence before NSCLC diagnosis versus current smokers with less than 1 year of smoking abstinence before NSCLC diagnosis
HR=hazard ratio. NSCLC=non-small-cell lung cancer. SHR=sub-distribution hazard ratio.

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Comment in

Smoking cessation and lung cancer: never too late to quit.
Murray RL, O'Dowd E. Murray RL, et al. Lancet Public Health. 2023 Sep;8(9):e664-e665. doi: 10.1016/S2468-2667(23)00158-5. Lancet Public Health. 2023. PMID: 37633673 No abstract available.

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Association between duration of smoking abstinence before non-small-cell lung cancer diagnosis and survival: a retrospective, pooled analysis of cohort studies

Affiliations

Association between duration of smoking abstinence before non-small-cell lung cancer diagnosis and survival: a retrospective, pooled analysis of cohort studies

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

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MeSH terms

Grants and funding

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Research Materials